Discovery – Methotrexate: Chemotherapy Treatment for Cancer

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Prior to the 1950s, treatment for the majority of cancers was limited to either surgery or the use of radiation. The discovery of the use of methotrexate in curing a rare cancer marked the first time a cancer had been cured. This led to the development of many of today’s common cancer treatments.

Intraocular levels of methotrexate after oral low-dose treatment in chronic uveitis.

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Puchta, Joachim; Hattenbach, Lars-Olof; Baatz, Holger

2005-01-01

To determine the intraocular levels of methotrexate in low-dose treatment of noninfectious uveitis. One day after oral administration, the methotrexate level was measured in the aqueous humor and serum of a patient with noninfectious uveitis, who underwent cataract surgery. A fluorescence polarization immunoassay was used for determination. After oral administration, methotrexate was only measurable in aqueous humor but not in serum. In uveitis, orally administered low-dose methotrexate reaches detectable levels in aqueous humor, even in the absence of detectable levels in serum. Copyright (c) 2005 S. Karger AG, Basel.

Palonosetron for the prevention of nausea and vomiting in children with acute lymphoblastic leukemia treated with high dose methotrexate

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Nadaraja, Sambavy; Mamoudou, Aissata Diop; Thomassen, Harald

2012-01-01

High dose methotrexate (HD-MTX), used in the treatment of children with acute lymphoblastic leukemia (ALL), is moderately emetogenic. First generation 5-HT(3) receptor antagonists are effective prophylactic agents but require multiple administrations. Palonosetron has a half life of 36-42 hours...... of palonosetron (5 µg/kg) for the prevention of chemotherapy-induced nausea and vomiting in children 18 years of age with ALL treated with HD-MTX, 5 g/m(2)....

An indirect comparison and cost per responder analysis of adalimumab, methotrexate and apremilast in the treatment of methotrexate-naïve patients with psoriatic arthritis.

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Betts, Keith A; Griffith, Jenny; Friedman, Alan; Zhou, Zheng-Yi; Signorovitch, James E; Ganguli, Arijit

2016-01-01

Apremilast was recently approved for the treatment of active psoriatic arthritis (PsA). However, no studies compare apremilast with methotrexate or biologic therapies, so its relative comparative efficacy remains unknown. This study compared the response rates and incremental costs per responder associated with methotrexate, apremilast, and biologics for the treatment of active PsA. A systematic literature review was performed to identify phase 3 randomized controlled clinical trials of approved biologics, methotrexate, and apremilast in the methotrexate-naïve PsA population. Using Bayesian methods, a network meta-analysis was conducted to indirectly compare rates of achieving a ≥20% improvement in American College of Rheumatology component scores (ACR20). The number needed to treat (NNT) and the incremental costs per ACR20 responder (2014 US$) relative to placebo were estimated for each of the therapies. Three trials (MIPA for methotrexate, PALACE-4 for apremilast, and ADEPT for adalimumab) met all inclusion criteria. The NNTs relative to placebo were 2.63 for adalimumab, 6.69 for apremilast, and 8.31 for methotrexate. Among methotrexate-naïve PsA patients, the 16 week incremental costs per ACR20 responder were $3622 for methotrexate, $26,316 for adalimumab, and $45,808 for apremilast. The incremental costs per ACR20 responder were $222,488 for apremilast vs. methotrexate. Among methotrexate-naive PsA patients, adalimumab was found to have the lowest NNT for one additional ACR20 response and methotrexate was found to have the lowest incremental costs per ACR20 responder. There was no statistical evidence of greater efficacy for apremilast vs. methotrexate. A head-to-head trial between apremilast and methotrexate is recommended to confirm this finding.

Measures of 6-mercaptopurine and methotrexate maintenance therapy intensity in childhood acute lymphoblastic leukemia

DEFF Research Database (Denmark)

Nielsen, Stine Nygaard; Grell, Kathrine; Nersting, Jacob

2016-01-01

PURPOSE: Normal white blood cell counts (WBC) are unknown in children with acute lymphoblastic leukemia (ALL). Accordingly, 6-mercaptopurine (6MP) and methotrexate (MTX) maintenance therapy is adjusted by a common WBC target of 1.5-3.0 × 10(9)/L. Consequently, the absolute degree...

Methotrexate osteopathy in long-term, low-dose methotrexate treatment for psoriasis and rheumatoid arthritis

NARCIS (Netherlands)

Zonneveld, I. M.; Bakker, W. K.; Dijkstra, P. F.; Bos, J. D.; van Soesbergen, R. M.; Dinant, H. J.

1996-01-01

In dermatology and rheumatology, methotrexate is frequently prescribed in low dosages per week; in oncology, high dosages per week are prescribed. Methotrexate osteopathy was first reported in children with leukemia treated with high doses of methotrexate. In animal studies, low doses of

Methotrexate in the treatment of peripheral arthritis in ulcerative colitis

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R. Scarpa

2011-06-01

Full Text Available Objective: To evaluate efficacy of methotrexate treatment in peripheral arthritis of ulcerative colitis. Methods: We studied 18 patients (10/8 M/F; mean age: 38.90 yrs; range: 21-65 yrs, with peripheral arthritis (14 with polyarticular, 4 with oligoarticular subset associate ulcerative colitis. Methotrexate 20 mg/week was administered in our patients, who were already receiving mesalazina for inflammatory bowel disease. At baseline, after 3 (T1, 6 (T2 and 12 months (T3 serological parameters (ESR and CRP, functional status (HAQ and disease activity (VAS, GH, Ritchie articular index were evaluated. Results: During the therapy a significant improvement was observed in disease activity, functional status and serological parameters since T1. ESR and CRP did not change at T2 and T3. Instead VAS, GH, Ritchie articular index and HAQ had a significant and gradual improvement from T1 to T3. Conclusion: Methotrexate treatment was efficacious in the treatment of peripheral arthritis associate ulcerative colitis. This drug induced improvement in disease activity, functional status and serological parameters after 3 months of therapy.

High Efficacy of Methotrexate in Patients with Recurrent Idiopathic Acute Anterior Uveitis: a Prospective Study.

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Bachta, Artur; Kisiel, Bartłomiej; Tłustochowicz, Mateusz; Raczkiewicz, Anna; Rękas, Marek; Tłustochowicz, Witold

2017-02-01

To evaluate prospectively the efficacy of methotrexate (MTX) in the treatment of recurrent idiopathic acute anterior uveitis (RIAAU). Nineteen out of 22 RIAAU patients completed the study (two patients withdrew their consent shortly after study initiation, one patient discontinued after 4 weeks because of the adverse effects). All patients were treated with MTX in a starting dose of 15 mg/week, increased to target dose of 25 mg/week after 4 weeks. In patients taking systemic corticosteroids (CS) the dose was gradually tapered (by 2.5 mg every week) until discontinuation. The mean follow-up period was 3.3 years (19-59 months). Sixteen patients (84 %) remained flare-free on MTX therapy. In the remaining three patients the mean interval between flares increased from 4.8 to 18.3 months. Systemic CS were tapered off in all patients. The number of acute anterior uveitis flares in the whole cohort decreased from 2.12 to 0.11/patient-year (p treatment of RIAAU.

Methotrexate: an option for preventing the recurrence of acute anterior uveitis.

Science.gov (United States)

Muñoz-Fernández, S; García-Aparicio, A M; Hidalgo, M V; Platero, M; Schlincker, A; Bascones, M L; Pombo, M; Morente, P; Sanpedro, J; Martín-Mola, E

2009-05-01

To evaluate the efficacy of methotrexate (MTX) in preventing the recurrence of acute anterior uveitis (AAU). This prospective, open, longitudinal study included patients from June 2002 to March 2005 who had either three or more episodes of AAU in the previous year, or a recurrence of AAU within 3 months before starting the trial. We excluded uveitis of infectious origin, masquerade syndromes, and patients with contraindications to MTX. The response criteria were defined as an absence of symptoms and the presence of a normal ophthalmologic examination. The study outcome compared the number of flare-ups of uveitis over an MTX-treated for 1 year to the number of flare-ups of the same group during the previous year without MTX. A total of 571 patients with uveitis were evaluated during the period of the study, and 10 fulfilled the inclusion criteria. One patient refused the treatment, and nine completed the study. The mean number of recurrences in the pre-MTX year was 3.4 (SD: 0.52), which was significantly reduced to 0.89 (SD: 1.17) in the year of treatment (P=0.011). MTX treatment seems to reduce the number of flare-ups in patients with recurrent AAU.

[Late sequelae of central nervous system prophylaxis in children with acute lymphoblastic leukemia: high doses of intravenous methotrexate versus radiotherapy of the central nervous system--review of literature].

Science.gov (United States)

Zając-Spychała, Olga; Wachowiak, Jacek

2012-01-01

Acute lymphoblastic leukemia is the most common malignancy in children. All current therapy regimens used in the treatment of childhood acute lymphoblastic leukemia include prophylaxis of the central nervous system. Initially it was thought that the best way of central nervous system prophylaxis is radiotherapy. But despite its effectiveness this method, may cause late sequelae and complications. In the programme currently used in Poland to treat acute lymphoblastic leukemia, prophylactic radiotherapy has been reduced by 50% (12 Gy) and is used only in patients stratified into the high risk group and in patients diagnosed as T-cell ALL (T-ALL). Complementary to radiotherapy, intrathecal methotrexate is given alone or in combination with cytarabine and hydrocortisone is given, as well as systemic chemotherapy with intravenous methotrexate is administered in high or medium doses (depending on risk groups and leukemia immunophenotype). Recent studies have shown that high dose irradiation of the central nervous system impairs cognitive development causing memory loss, visuomotor coordination impairment, attention disorders and reduction in the intelligence quotient. It has been proved that the degree of cognitive impairment depends on the radiation dose directed to the medial temporal lobe structures, particularly in the hippocampus and the surrounding cortex. Also, methotrexate used intravenously in high doses, interferes with the metabolism of folic acid which is necessary for normal development and the optimal functioning of neurons in the central nervous system. It has been proved that patients who have been treated with high doses of methotrexate are characterized by reduced memory skills and a lower intelligence quotient. The literature data concerning long term neuroanatomical abnormalities and neuropsychological deficits are ambiguous, and there is still no data concerning current methods of central nervous system prophylaxis with low doses of irradiation in

Glucarpidase treatment for methotrexate intoxication: a case report and review of the literature

NARCIS (Netherlands)

Boelens, A. D.; Mathôt, R. A. A.; Vlaar, A. P. J.; Bouman, C. S. C.

2018-01-01

High-dose methotrexate (MTX) induced acute kidney injury can lead to sustained high systemic MTX levels and severe toxicity. A 39-year-old man with lymphoblastic T-cell lymphoma was admitted to our intensive care unit with elevated serum creatinine and prolonged high serum MTX levels. Standard

Cyclosporin-Methotrexate Compared with Cyclosporin-Methotrexate-Methylprednisolone Therapy for the Prophylaxis of Acute Graft-Versus Host Disease

International Nuclear Information System (INIS)

Khattab, N.F.

2010-01-01

Acute graft-versus host (GVHD) disease is a common immunologic complication, which occurs in 40-50% of the recipients of allogenic stem cell transplantation (SCT). The role of corticosteroid in the prevention of GVHD is not well established. We report here a study to determine whether the addition of methylprednisolone to the combination of cyclosporine (CSA) and methotrexate (MTX), methylp-rednisolone (MP) for the prophylaxis of acute GVHD would further decrease the incidence of acute GVHD. A group of patients (25 patients with acute myeloid leukemia (AML) and 12 patients with acute lymphocytic leukemia (ALL) that received CSA/MTX/MP started from 2004 to 2008, were compared to a historical group of patients (19 patient with acute myeloid leukemia (AML) and 12 patients with acute lymphocytic leukemia (ALL) that received GVHD prophylaxis in the form of CSA/MTX only from 1999 to 2003). The primary endpoint in this study was the develop-ment of GVHD and the secondary end point was overall and disease free survival. Both groups of patients were matched for age, sex, donor recipient sex, low risk patients and high risk patients. Although the incidence of acute GVHD in the MP -ve group was 35% versus 24% in the MP+ve group, there was no significant difference between them. The overall survival showed a significant difference between the 2 groups (p<0.05). It was 48% for the 2 drug regimen (CSA/MTX) vs. 81% for the three drug regimen (CSA/MTX/MP). There was a significant decrease in the relapse rate in patients on CSA/MTX/MP (p<0.05). In conclusion, the addition of MP (methylprednis-olone) to the combination of CSA/MTX did not affect the incidence of acute GVHD significantly in allogeneic SCT but surprisingly the incidence of survival and relapse was markedly increased and decreased respectively

Extracorporeal photochemotherapy and methotrexate in the treatment of atypical oral lichen planus

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A. V. Molochkov

2017-01-01

Full Text Available Background: Some authors have successfully used methotrexate in the treatment of atypical oral lichen planus (LP and noted its good tolerability. High clinical efficacy of the extracorporeal photochemotherapy (ECP has been also reported in the treatment of such patients. However, there is no information on the long-term results of methotrexate and ECP and their combination in the treatment of atypical LP. Aim: To study clinical efficacy and long-term results of the combination of routine therapy with the ECP course and a single injection of methotrexate at a dose of 10 mg in patients with atypical LP of the oral cavity and the skin. Materials and methods: This was a prospective study with an active control. Eighteen (18 patients with various forms of atypical LP of the oral cavity (hypertrophic, erosive/ulcerative, exudative/hyperemic forms and the skin (hypertrophic, pigmented, atrophic, follicular forms were administered the combination of routine therapy (chloroquine, doxycycline, vitamin B6, topical corticosteroids, an ECP course, and a single injection of methotrexate at a dose of 10 mg. Two hours before the ECP session all patients were given 8-methoxypsoralen. Peripheral mononuclear cells were isolated with a cell separator and treated with ultraviolet radiation (λ = 320–400 nm, then the monocyte cell mass was re-infused to the patient. The treatment course included 4 sessions performed every other day. A single injection of methotrexate was given in the middle of the ECP course. Clinical efficacy was assessed with the Thongprasom scale of activity of the disease and by visual analog scale (VAS for pain assessment in patients with oral lesions. Results: The treatment was well tolerated and was not associated with methotrexate-related immune abnormalities. At one month after the 4th ECP session, the mean Thongprasom score was decreased from 5 to 2.2 ± 1.2 (p < 0.001. At Week 24 after the treatment, 15 (83.2% of

Methotrexate osteopathy

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Schwartz, A.M.; Leonidas, J.C.

1984-01-01

Methotrexate osteopathy is an uncommon complication of long-term oral maintenance therapy for childhood neoplasms, most commonly acute lymphocytic leukemia. It is characterized by severe lower extremity pain and by osteoporosis particularly involving the lower extremities and thick dense provisional zones of calcification and growth arrest lines resembling scurvy. Fractures may occur. The appearance must be distinguished from recurrent or metastatic disease.

Methotrexate osteopathy

International Nuclear Information System (INIS)

Schwartz, A.M.; Leonidas, J.C.; Tufts Univ., Boston, MA

1984-01-01

Methotrexate osteopathy is an uncommon complication of long-term oral maintenance therapy for childhood neoplasms, most commonly acute lymphocytic leukemia. It is characterized by severe lower extremity pain and by osteoporosis particularly involving the lower extremities and thick dense provisional zones of calcification and growth arrest lines resembling scurvy. Fractures may occur. The appearance must be distinguished from recurrent or metastatic disease. (orig.)

EFFICACY OF LOW-DOSE METHOTREXATE TREATMENT IN BIRDSHOT CHORIORETINOPATHY

NARCIS (Netherlands)

Rothova, Aniki; Ossewaarde-van Norel, Annette; Los, Leonoor I.; Berendschot, Tos T. J. M.

Purpose: To ascertain the effect of treatment with methotrexate (MTX) on the visual prognosis of birdshot chorioretinopathy (BSCR). Methods: Retrospective case series of 76 consecutive patients with HLA-A29-positive BSCR, of whom 46 were followed for at least 5 years and 18 for longer than 10 years.

Computed tomographic diagnosis of methotrexate leukoencephalopathy, developed in children with acute lymphocytic leukemia

International Nuclear Information System (INIS)

Seguchi, Michiko

1983-01-01

The difference of Hounsfield units between the white and gray matter are highly reliable indexes for the numerical analysis of infant cranial CT. These indexes were evaluated in 239 healthy children at ages ranging from 1 to 15 years. CT findings of white matter changes due to methotrexate were evaluated numerically in 80 children with acute lymphatic leukemia. This analysis resulted in detection of transient, or preclinical, slight pathological changes in the white matter. This method was also considered to give objectivity to evaluation of the changes in CT. (Ueda, J.)

Individualized toxicity-titrated 6-mercaptopurine increments during high-dose methotrexate consolidation treatment of lower risk childhood acute lymphoblastic leukemia

DEFF Research Database (Denmark)

Frandsen, Thomas Leth; Abrahamsson, Jonas; Lausen, Birgitte Frederiksen

2011-01-01

This study explored the feasibility and toxicity of individualized toxicity-titrated 6-mercaptopurine (6MP) dose increments during post-remission treatment with High-dose methotrexate (HDM) (5000 mg/m2, ×3) in 38 patients with Childhood (ALL). Patients were increased in steps of 25 mg 6MP/m2 per...... the remaining patients (P = 0·03). This study shows individualized toxicity-titrated 6MP dosing during consolidation is feasible without increased risk of toxicity....

EEG with extreme delta brush in young female with methotrexate neurotoxicity supports NMDA receptor involvement

DEFF Research Database (Denmark)

Schmidt, Lisbeth Samsø; Kjær, Troels W; Schmiegelow, Kjeld

2017-01-01

Sub-acute neurotoxicity is a well-known complication to high-dose and intrathecal methotrexate (MTX) treatment of children with leukemia. Symptoms can be treated safely by dextromethorphan, a non-competitive antagonist to N-methyl-D-aspartic acid receptor (NMDAR). In a female with subacute MTX...

Methotrexate-induced side effects are not due to differences in pharmacokinetics in children with Down syndrome and acute lymphoblastic leukemia

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Buitenkamp, Trudy D.; Mathôt, Ron A. A.; de Haas, Valerie; Pieters, Rob; Zwaan, C. Michel

2010-01-01

Children with Down syndrome have an increased risk of developing acute lymphoblastic leukemia and a poor tolerance of methotrexate. This latter problem is assumed to be caused by a higher cellular sensitivity of tissues in children with Down syndrome. However, whether differences in pharmacokinetics

Methotrexate for ocular inflammatory diseases.

Science.gov (United States)

Gangaputra, Sapna; Newcomb, Craig W; Liesegang, Teresa L; Kaçmaz, R Oktay; Jabs, Douglas A; Levy-Clarke, Grace A; Nussenblatt, Robert B; Rosenbaum, James T; Suhler, Eric B; Thorne, Jennifer E; Foster, C Stephen; Kempen, John H

2009-11-01

To evaluate the outcome of treatment with methotrexate for noninfectious ocular inflammation. Retrospective cohort study. Patients with noninfectious ocular inflammation managed at 4 tertiary ocular inflammation clinics in the United States observed to add methotrexate as a single, noncorticosteroid immunosuppressive agent to their treatment regimen, between 1979 and 2007, inclusive. Participants were identified from the Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study. Demographic and clinical characteristics, including dosage, route of administration of methotrexate, and main outcome measures, were obtained for every eye of every patient at every visit via medical record review by trained expert reviewers. Control of inflammation, corticosteroid-sparing effects, and incidence of and reason for discontinuation of therapy. Among 384 patients (639 eyes) observed from the point of addition of methotrexate to an anti-inflammatory regimen, 32.8%, 9.9%, 21.4%, 14.6%, 15.1%, and 6.3%, respectively, had anterior uveitis, intermediate uveitis, posterior or panuveitis, scleritis, ocular mucous membrane pemphigoid, and other forms of ocular inflammation. In these groups, complete suppression of inflammation sustained for >or=28 days was achieved within 6 months in 55.6%, 47.4%, 38.6%, 56.4%, 39.5%, and 76.7%, respectively. Corticosteroid-sparing success (sustained suppression of inflammation with prednisone Methotrexate was discontinued within 1 year by 42% of patients. It was discontinued owing to ineffectiveness in 50 patients (13%); 60 patients (16%) discontinued because of side effects, which typically were reversible with dose reduction or discontinuation. Remission was seen in 43 patients, with 7.7% remitting within 1 year of treatment. Our data suggest that adding methotrexate to an anti-inflammatory regimen not involving other noncorticosteroid immunosuppressive drugs is moderately effective for management of inflammatory activity and for achieving

PUVA and methotrexate therapy of psoriasis: how closely do dermatology departments follow treatment guidelines? Psoriasis Audit Workgroup of the British Association of Dermatologists.

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Bilsland, D J; Rhodes, L E; Zaki, I; Wilkinson, S M; McKenna, K E; Handfield-Jones, S E; Williams, R E

1994-08-01

Following publication of treatment guidelines for patients with psoriasis, a six-centre audit was undertaken to assess current therapeutic practice for two second-line treatments, PUVA and methotrexate. The audit consisted of random sampling of casenotes by external auditors from a paired dermatology department, and assessment by questionnaire. One hundred and eight PUVA and 118 methotrexate casenotes were audited. The commonest indications for treatment were: (a) failure of tropical therapy--PUVA (mean 81% of casenotes), methotrexate (84%); (b) repeated hospital admissions--PUVA (16%), methotrexate (25%). For both PUVA and methotrexate, some aspects of treatment were well documented: PUVA--psoralen dosage (91%), response to PUVA (89%), cumulative lifetime UVA dosage (81%); methotrexate--pretreatment assessment of full blood count (91%), urea and electrolytes (85%), liver function tests (84%). For other aspects documentation was less complete: PUVA--no documentation of presence/absence of skin cancer history (66%), note of photoactive drugs (32%); methotrexate--concurrent medication (69%), history of presence/absence of liver disease (36%). Another aspect which was poorly documented in both PUVA and methotrexate notes was whether advice on contraception/fertility had been given. There was no indication in 29 of 32 casenotes of females of child-bearing age receiving PUVA, and 52 of 63 case notes of relevant patients on methotrexate. This project has demonstrated that formal, multicentre audit based on published guidelines is a practical proposition.

Failure Rate of Single Dose Methotrexate in Managment of Ectopic Pregnancy

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Feras Sendy

2015-01-01

Full Text Available Background. One of the treatment modalities for ectopic pregnancy is methotrexate. The purpose of this study is to identify the failure rate of methotrexate in treating patients with ectopic pregnancy as well as the risk factors leading to treatment failure. Methods. A retrospective chart review of 225 patients who received methotrexate as a primary management option for ectopic pregnancy. Failure of single dose of methotrexate was defined as drop of BHCG level less than or equal to 14% in the seventh day after administration of methotrexate. Results. 225 patients had methotrexate. Most of the patients (151 (67% received methotrexate based on the following formula: f 50 mg X body surface area. Single dose of methotrexate was successful in 72% (162/225 of the patients. 28% (63/225 were labeled as failure of single dose of methotrexate because of suboptimal drop in BhCG. 63% (40/63 of failure received a second dose of methotrexate, and 37% (23/63 underwent surgical treatment. Among patient who received initial dose of methotrexate, 71% had moderate or severe pain, and 58% had ectopic mass size of more than 4 cm on ultrasound. Conclusion. Liberal use of medical treatment of ectopic pregnancy results in 71% success rate.

Failure rate of single dose methotrexate in managment of ectopic pregnancy.

Science.gov (United States)

Sendy, Feras; AlShehri, Eman; AlAjmi, Amani; Bamanie, Elham; Appani, Surekha; Shams, Taghreed

2015-01-01

Background. One of the treatment modalities for ectopic pregnancy is methotrexate. The purpose of this study is to identify the failure rate of methotrexate in treating patients with ectopic pregnancy as well as the risk factors leading to treatment failure. Methods. A retrospective chart review of 225 patients who received methotrexate as a primary management option for ectopic pregnancy. Failure of single dose of methotrexate was defined as drop of BHCG level less than or equal to 14% in the seventh day after administration of methotrexate. Results. 225 patients had methotrexate. Most of the patients (151 (67%)) received methotrexate based on the following formula: f 50 mg X body surface area. Single dose of methotrexate was successful in 72% (162/225) of the patients. 28% (63/225) were labeled as failure of single dose of methotrexate because of suboptimal drop in BhCG. 63% (40/63) of failure received a second dose of methotrexate, and 37% (23/63) underwent surgical treatment. Among patient who received initial dose of methotrexate, 71% had moderate or severe pain, and 58% had ectopic mass size of more than 4 cm on ultrasound. Conclusion. Liberal use of medical treatment of ectopic pregnancy results in 71% success rate.

Effects of repeated administration of chemotherapeutic agents tamoxifen, methotrexate, and 5-fluorouracil on the acquisition and retention of a learned response in mice

Science.gov (United States)

Foley, John J.; Clark-Vetri, Rachel; Raffa, Robert B.

2011-01-01

Rationale A number of cancer chemotherapeutic agents have been associated with a loss of memory in breast cancer patients although little is known of the causality of this effect. Objectives To assess the potential cognitive effects of repeated exposure to chemotherapeutic agents, we administered the selective estrogen receptor modulator tamoxifen or the antimetabolite chemotherapy, methotrexate, and 5-fluorouracil, alone and in combination to mice and tested them in a learning and memory assay. Methods Swiss-Webster male mice were injected with saline, 32 mg/kg tamoxifen, 3.2 or 32 mg/kg methotrexate, 75 mg/kg 5-fluorouracil, 3.2 or 32 mg/kg methotrexate in combination with 75 mg/kg 5-fluorouracil once per week for 3 weeks. On days 23 and 24, mice were tested for acquisition and retention of a nose-poke response in a learning procedure called autoshaping. In addition, the acute effects of tamoxifen were assessed in additional mice in a similar procedure. Results The chemotherapeutic agents alone and in combination reduced body weight relative to saline treatment over the course of 4 weeks. Repeated treatment with tamoxifen produced both acquisition and retention effects relative to the saline-treated group although acute tamoxifen was without effect except at a behaviorally toxic dose. Repeated treatment with methotrexate in combination with 5-fluorouracil produced effects on retention, but the magnitude of these changes depended on the methotrexate dose. Conclusions These data demonstrate that repeated administration of tamoxifen or certain combination of methotrexate and 5-fluorouracil may produce deficits in the acquisition or retention of learned responses which suggest potential strategies for prevention or remediation might be considered in vulnerable patient populations. PMID:21537942

Methotrexate use in allergic contact dermatitis: a retrospective study.

Science.gov (United States)

Patel, Ashaki; Burns, Erin; Burkemper, Nicole M

2018-03-01

Methotrexate, a folate antimetabolite, is used to treat atopic dermatitis and psoriasis. Although methotrexate's therapeutic efficacy has been noted in the literature, there are few data on the efficacy of methotrexate treatment for allergic contact dermatitis. To evaluate the efficacy and tolerability of methotrexate in treating allergic contact dermatitis at a single institution, and also to assess methotrexate efficacy in patients with chronic, unavoidable allergen exposure. We performed a retrospective chart review of 32 patients diagnosed with allergic contact dermatitis by positive patch test reactions, and who received treatment with methotrexate from November 2010 to November 2014. Demographic and treatment-associated data were collected from electronic medical records. Ten patients were identified as allergen non-avoiders secondary to their occupation, and were subgrouped as such. Seventy-eight per cent (25/32) of patients showed either a partial or a complete response. Methotrexate had a comparable efficacy rate in the allergen non-avoiders subset, at 10 of 10. Of the 32 patients, 23% (5/22) had complete clearance of their dermatitis, and 1/10 of allergen non-avoiders had complete clearance of their dermatitis. Methotrexate is a well-tolerated and effective treatment for allergic contact dermatitis, and shows comparable efficacy to immunomodulatory agents such as cyclosporine and azathioprine, with robust efficacy despite persistent allergen exposure in patients with allergic contact dermatitis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Methotrexate for the Treatment of Pediatric Crohn's Disease: A Systematic Review and Meta-analysis.

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Colman, Ruben J; Lawton, Rachel C; Dubinsky, Marla C; Rubin, David T

2018-04-23

Methotrexate (MTX) is an immunomodulator used for the treatment of pediatric inflammatory bowel disease (IBD). There are currently no RCTs that assess the treatment efficacy of methotrexate within the pediatric IBD patient population. This systematic review and meta-analysis assesses the efficacy of MTX therapy among the existing pediatric literature. A systematic literature search was performed using MEDLINE and the Cochrane library from inception until March 2016. Synonyms for 'pediatric', 'methotrexate' and 'IBD' were utilized as both free text and MESH search terms. The studies included contained clinical remission (CR) rates for MTX treatment of pediatric IBD patients 18 yrs old, as mono- or combination therapy. Case studies with <10 patients were excluded. Quality assessment was performed with the Newcastle-Ottawa Scale. Meta-analysis calculated pooled CR rates. A random-effects meta-analysis with forest plots was performed using R. Fourteen (11 monotherapy, 1 combination therapy, 2 both; n = 886 patients) observational studies were eligible out of 202 studies. No interventional studies were identified. The pooled achieved CR rate for pediatric CD patients on monotherapy within 3-6 months was 57.7% (95% CI 48.2-66.6%), (P =0.22; I2 = 29.8%). The CR was 37.1% (95% CI 29.5-45.5%), (P = 0.20; I2 = 37.4%) for maintenance therapy at 12 months. Sub-analysis could not identify CR differences between MTX administration types, thiopurine exposure. This meta-analysis demonstrated that, over 50% of pediatric Crohn's disease patients induced with methotrexate achieved clinical remission, while 12-month remission rate was only 37%. Prospective controlled interventional trials should assess treatment efficacy among patient subgroups. 10.1093/ibd/izy078_video1izy078.video15774883936001.

A U-HPLC-ESI-MS/MS-based stable isotope dilution method for the detection and quantitation of methotrexate in plasma

NARCIS (Netherlands)

E. den Boer (Ethan); S.G. Heil (Sandra); B.D. van Zelst (Bertrand); P. Schneider (Petra); B.C.P. Koch (Birgit); M.L. te Winkel (Mariël Lizet); M.M. van den Heuvel-Eibrink (Marry); T.M. Luider (Theo); R. de Jonge (Robert)

2012-01-01

textabstractINTRODUCTION: High-dose methotrexate (MTX) is used in the treatment of proliferative diseases such as acute lymphoblastic leukemia. Therapeutic drug monitoring of plasma MTX is important to monitor efficacy and adverse events. The authors aimed to develop a liquid chromatography,

Novel methotrexate soft nanocarrier/fractional erbium YAG laser combination for clinical treatment of plaque psoriasis.

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Ramez, Shahenda A; Soliman, Mona M; Fadel, Maha; Nour El-Deen, Faisal; Nasr, Maha; Youness, Eman R; Aboel-Fadl, Dalea M

2018-02-15

Psoriasis is a commonly encountered chronic dermatological disease, presenting with inflammatory symptoms in patients. Systemic treatment of psoriasis is associated with several adverse effects, therefore the development of a customized topical treatment modality for psoriasis would be an interesting alternative to systemic delivery. The therapeutic modality explored in this article was the comparative treatment of psoriatic patients using nanoparticulated methotrexate in the form of jojoba oil-based microemulsion with or without fractional erbium YAG laser. Assessment parameters included follow-up photography for up to 8 weeks of treatment, estimation of the psoriasis severity [TES (thickness, erythema, scales)] score, and histopathological skin evaluation. The prepared methotrexate microemulsion was clinically beneficial and safe in treatment of psoriasis vulgaris. The concomitant use of the fractional laser provided improvement in the psoriatic plaques within shorter time duration (3 weeks compared to 8 weeks of treatment), presenting an alternative topical treatment modality for psoriasis vulgaris.

Computed tomography of the brain following prophylactic treatment with irradiation therapy and intraspinal metho-trexate in children with acute lymphoblastic leukemia

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Lund, E.; Hamborg-Pedersen, B.

1984-01-01

In 28 children with acute lymphoblastic leukemia (ALL) computed tomography (CT) was performed in order to demonstrate possible cerebral changes following treatment with prophylactic irradiation and intraspinal methotrexate (MTX). The time of CT-scan examination varied from 1 year and 1 month to 10 years and 1 month after diagnosis of ALL. The age of the children ranged from 3 years and 11 months to 14 years and 5 months. Six children had normal CT scans, 12 children had slight atrophylike changes, and nine had severe cerebral atrophy. Two patients in the latter group presented an enlarged ventricular system as well. In one patient intracerebral calcification was the only pathologic finding. The severe changes were seen in children of all age groups, but predominantly-in children with a short duration of their disease, severe symptoms, and frequent marrow relapse. Changes induced by steroid therapy may be reversible. No satisfactory explanation of the demonstrated cerebral pathologic findings can be given, except that they are the consequences of the combination of total therapy and severity of disease in the individual patient. Measurement of attenuation coefficients in grey and white matter shows increasing values with age during childhood. A combination of decreasing attenuation coefficients, especially in the white matter, and the finding of severe atrophy seems to be a bad prognostic sign. (orig.)

The effects of combined therapy of rheumatoid arthritis on the acute phase reactants.

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Rexhepi, Sylejman; Rexhepi, Mjellma; Sahatçiu-Meka, Vjollca; Pllana, Ejup; Dragusha, Gani; Gashi, Masar; Rexhepi, Blerta

2009-01-01

The paper presents the results of studies of acute phase reactants in the 60 treated patients with rheumatoid arthritis. Patients were divided into two groups, depending on the applied treatment: group I (n = 30) was treated with methotrexate, sulfasalazine and hydroxychloroquine, and group II (n = 30) with methotrexate. The results of our study shows that there is a statistically significant reduction in the value of acute phase reactants and clinical parameters after treatment in both investigated groups of patients, and also a significant statistical difference between the first and second group of treated patients.

Successful combination treatment of a patient with progressive juvenile localized scleroderma (morphea) using imatinib, corticosteroids, and methotrexate.

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Inamo, Yasuji; Ochiai, Toyoko

2013-01-01

We report a case of progressive juvenile localized scleroderma (JLS or morphea) treated with a combination of imatinib, corticosteroids, and methotrexate. This therapy halted the progressive skin thickening and the hand and finger joint deformity in the early stages of the disease. We conclude that imatinib used in addition to standard treatment with systemic corticosteroids and methotrexate may be of therapeutic benefit for individuals with JLS. © 2012 Wiley Periodicals, Inc.

Mycophenolate mofetil after methotrexate failure or intolerance in the treatment of scleritis and uveitis.

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Sobrin, Lucia; Christen, William; Foster, C Stephen

2008-08-01

To evaluate the outcomes of treatment with mycophenolate mofetil in patients with scleritis and uveitis refractory to or intolerant of methotrexate. Retrospective noncomparative case series. Eighty-five patients with scleritis and/or uveitis who failed with or did not tolerate methotrexate and were subsequently treated with mycophenolate mofetil between 1998 and 2006. We reviewed medical records of patients who were treated with mycophenolate mofetil after methotrexate intolerance or failure at one tertiary uveitis referral practice. We recorded dose and duration of methotrexate and mycophenolate mofetil therapy, inflammation grade, Snellen visual acuity (VA), use of other immunomodulatory therapy, and adverse events. Multivariate logistic regression was used to identify factors associated with inflammation control. Control of inflammation, steroid-sparing effect, VA, and adverse effects were assessed. Inflammation was controlled with mycophenolate mofetil in 47 patients (55%), with 5 achieving durable remission off all medication. In multivariate logistic regression analysis that adjusted for gender and age, the odds of inflammation control were lower for patients with scleritis (odds ratio [OR], 0.19; 95% confidence interval [CI], 0.04-0.93; P = 0.04) than for patients without scleritis. Among patients without scleritis, the odds of inflammation control were lower for patients with juvenile idiopathic arthritis (JIA)-associated uveitis (OR, 0.14; CI, 0.02-0.81, P = 0.03) compared to patients without JIA-associated uveitis. Eight of the 11 patients (73%) who were taking concomitant prednisone were able to taper their dose to methotrexate. The odds of inflammation control were less in patients with the diagnoses of scleritis and JIA.

The combination of etanercept and methotrexate increases the effectiveness of treatment in active psoriasis despite inadequate effect of methotrexate therapy

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Zachariae, Claus; Mørk, Nils-Jørgen; Reunala, Timo

2008-01-01

Many patients with moderate-to-severe plaque psoriasis do not respond adequately to methotrexate monotherapy. This pilot study, with a small patient population, was performed to evaluate the effectiveness and safety of etanercept and methotrexate combination in patients with plaque psoriasis...

Hyper-alkalinization without hyper-hydration for the prevention of high-dose methotrexate acute nephrotoxicity in patients with osteosarcoma.

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Mir, Olivier; Ropert, Stanislas; Babinet, Antoine; Alexandre, Jérôme; Larousserie, Frédérique; Durand, Jean-Philippe; Enkaoua, Eric; Anract, Philippe; Goldwasser, François

2010-11-01

To evaluate the reliability and renal safety of an original schedule of high-dose methotrexate (HDMTX) administration with hyper-alkalinization, and without hyper-hydration. Patients with osteosarcoma received HDMTX (8-12 g/m(2)) as a 4-h infusion. Hypertonic 8.4% sodium bicarbonate was infused prior to HDMTX, then once daily for 3 days. Methotrexate serum concentrations were measured at hour 4 (Cmax), hour 24, hour 48, and hour 72. Urinary pH was measured on each miction. Serum creatinine was assessed on days 1, 3, and 8. Twenty-six patients (median age: 18 years, range: 15-25) received a total of 344 cycles of HDMTX, including 16 patients treated in an outpatient basis. Urinary pH remained constantly higher than 7.5 in all patients. Grade 1 creatininemia toxicity was observed in 31 cycles (9%), and grade 2 creatinine toxicity was observed in one patient. No episode of acute severe nephrotoxicity was observed. No significant worsening was observed in serum creatinine and calculated creatinine clearance from baseline to the end of therapy (P = 0.74). The main extra-renal toxicity was alkalinization-related hypokalemia from H48. No re-hospitalization was required. Hyper-alkalinization appears an efficient and reliable method to prevent the acute renal toxicity of HDMTX and allows its safe administration in the outpatient setting.

Adipose-derived stem cells retain their regenerative potential after methotrexate treatment

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Beane, Olivia S.; Fonseca, Vera C.; Darling, Eric M.

2014-01-01

In musculoskeletal tissues like bone, chemotherapy can impair progenitor cell differentiation and proliferation, resulting in decreased bone growth and mineralization throughout a patient's lifetime. In the current study, we investigated the effects of chemotherapeutics on adipose-derived stem cell (ASC) function to determine whether this cell source could be a candidate for repairing, or even preventing, chemotherapy-induced tissue damage. Dose-dependent proliferation rates of ASCs and normal human fibroblasts (NHFs) were quantified after treatment with cytarabine (CY), etoposide (ETO), methotrexate (MTX), and vincristine (VIN) using a fluorescence-based assay. The influence of MTX on the multipotency of ASCs and freshly isolated stromal vascular fraction (SVF) cells was also evaluated using lineage-specific stains and spectrophotometry. ASC and NHF proliferation were equally inhibited by exposure to CY and ETO; however, when treated with MTX and VIN, ASCs exhibited greater resistance. This was especially apparent for MTX-treated samples, with ASC proliferation showing no inhibition for clinically relevant MTX doses ranging from 0.1 to 50 μM. Additional experiments revealed that the differentiation potential of ASCs was not affected by MTX treatment and that upregulation of dihydrofolate reductase possibly contributed to this response. Moreover, SVF cells, which include ASCs, exhibited similar resistance to MTX impairment, with respect to cellular proliferation, clonogenicity, and differentiation capability. Therefore, we have shown that the regenerative properties of ASCs resist the cytotoxicity of MTX, identifying these cells as a potential key for repairing musculoskeletal damage in patients undergoing chemotherapy. - Highlights: • Long-term effects of chemotherapeutics can include musculoskeletal dysfunction. • A screen of common drugs showed disparate effects on ASCs and fibroblasts. • One drug, methotrexate, did not impair ASC growth

Adipose-derived stem cells retain their regenerative potential after methotrexate treatment

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Beane, Olivia S. [Center for Biomedical Engineering, Brown University, Providence, RI (United States); Fonseca, Vera C. [Department of Molecular Pharmacology, Physiology, and Biotechnology, Brown University, Providence, RI (United States); Darling, Eric M., E-mail: Eric_Darling@brown.edu [Center for Biomedical Engineering, Brown University, Providence, RI (United States); Department of Molecular Pharmacology, Physiology, and Biotechnology, Brown University, Providence, RI (United States); Department of Orthopaedics, Brown University, Providence, RI (United States); School of Engineering, Brown University, Providence, RI (United States)

2014-10-01

In musculoskeletal tissues like bone, chemotherapy can impair progenitor cell differentiation and proliferation, resulting in decreased bone growth and mineralization throughout a patient's lifetime. In the current study, we investigated the effects of chemotherapeutics on adipose-derived stem cell (ASC) function to determine whether this cell source could be a candidate for repairing, or even preventing, chemotherapy-induced tissue damage. Dose-dependent proliferation rates of ASCs and normal human fibroblasts (NHFs) were quantified after treatment with cytarabine (CY), etoposide (ETO), methotrexate (MTX), and vincristine (VIN) using a fluorescence-based assay. The influence of MTX on the multipotency of ASCs and freshly isolated stromal vascular fraction (SVF) cells was also evaluated using lineage-specific stains and spectrophotometry. ASC and NHF proliferation were equally inhibited by exposure to CY and ETO; however, when treated with MTX and VIN, ASCs exhibited greater resistance. This was especially apparent for MTX-treated samples, with ASC proliferation showing no inhibition for clinically relevant MTX doses ranging from 0.1 to 50 μM. Additional experiments revealed that the differentiation potential of ASCs was not affected by MTX treatment and that upregulation of dihydrofolate reductase possibly contributed to this response. Moreover, SVF cells, which include ASCs, exhibited similar resistance to MTX impairment, with respect to cellular proliferation, clonogenicity, and differentiation capability. Therefore, we have shown that the regenerative properties of ASCs resist the cytotoxicity of MTX, identifying these cells as a potential key for repairing musculoskeletal damage in patients undergoing chemotherapy. - Highlights: • Long-term effects of chemotherapeutics can include musculoskeletal dysfunction. • A screen of common drugs showed disparate effects on ASCs and fibroblasts. • One drug, methotrexate, did not impair ASC growth

Studies on the assessment of neurotoxicity in children with acute lymphoblastic leukemia

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Muchi, H.; Satoh, T.; Yamamoto, K.; Karube, T.; Miyao, M.

1987-01-01

Central nervous system (CNS) prophylaxis caused a remarkable reduction in the incidence of CNS disease, however there has evolved a growing concern regarding the immediate or late toxicities to the developing CNS. Twenty-eight children with acute lymphoblastic leukemia who survived for more than 2 years were examined for the assessment of neurotoxicity induced by CNS prophylaxis and its treatment. The patients were stratified into three groups: Stratum I, prophylaxis with methotrexate; Stratum II, prophylaxis with cranial irradiation with methotrexate; and Stratum III, with CNS leukemia. Once CNS disease developed the sequelae were frequent and severe, due to the elevated methotrexate levels in the cerebrospinal fluid. CNS prophylaxis with intermediate-dose methotrexate was less toxic to the developing CNS than prophylactic cranial irradiation, especially in children under 5 years of age. Electroencephalograms and evoked potentials are likely to find increasing application in defining the CNS sequelae of acute lymphoblastic leukemia in children and its treatment. Although the sample size was small, the findings delineate specific areas of neurotoxicity

Four-year experience with methotrexate exposures.

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LoVecchio, Frank; Katz, Kenneth; Watts, David; Wood, Ian

2008-09-01

Unintentional methotrexate (MTX) acute oral overdose is rarely reported. We conducted a retrospective chart review of all human exposure calls (>150,000 charts) for MTX ingestions reported to our Poison Center during 2000-2003. Thirteen patients met the criteria. The average amount of MTX ingested was 13.03 mg (data from 7 cases), and the average patient age was 43 years (20 months to 80 years). No significant toxicities occurred. Although intravenous MTX toxicity can be severe, this does not appear to be a phenomenon associated with either acute unintentional or suicidal oral ingestion.

Successful Treatment of Fanconi Anemia and T-Cell Acute Lymphoblastic Leukemia

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Terrie Flatt

2012-01-01

Full Text Available Fanconi anemia is associated with an increased risk of malignancy. Patients are sensitive to the toxic effects of chemotherapy. We report the case of a patient with Fanconi anemia who developed T-cell acute lymphoblastic leukemia. He experienced chemotherapy-related complications including prolonged neutropenia, grade IV vincristine neuropathy, and disseminated aspergillosis. He was successfully treated with modified dosing of cytarabine and intrathecal methotrexate followed by allogeneic bone marrow transplant. The aspergillosis was treated with systemic antifungal treatment and surgical resection. Now 30 months after bone marrow transplant the patient is without evidence of aspergillosis or leukemia.

Efficacy and safety of tofacitinib monotherapy, tofacitinib with methotrexate, and adalimumab with methotrexate in patients with rheumatoid arthritis (ORAL Strategy): a phase 3b/4, double-blind, head-to-head, randomised controlled trial.

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Fleischmann, Roy; Mysler, Eduardo; Hall, Stephen; Kivitz, Alan J; Moots, Robert J; Luo, Zhen; DeMasi, Ryan; Soma, Koshika; Zhang, Richard; Takiya, Liza; Tatulych, Svitlana; Mojcik, Christopher; Krishnaswami, Sriram; Menon, Sujatha; Smolen, Josef S

2017-07-29

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. The Oral Rheumatoid Arthritis triaL (ORAL) Strategy aimed to assess the comparative efficacy of tofacitinib monotherapy, tofacitinib plus methotrexate, and adalimumab plus methotrexate for the treatment of rheumatoid arthritis in patients with a previous inadequate response to methotrexate. ORAL Strategy was a 1 year, double-blind, phase 3b/4, head-to-head, non-inferiority, randomised controlled trial in patients aged 18 years or older with active rheumatoid arthritis despite methotrexate therapy. Patients were randomly assigned (1:1:1) to receive oral tofacitinib (5 mg twice daily) monotherapy, oral tofacitinib (5 mg twice daily) plus methotrexate, or subcutaneous adalimumab (40 mg every other week) plus methotrexate at 194 centres in 25 countries. Eligible patients received live zoster vaccine at investigators' discretion. The primary endpoint was the proportion of patients who attained an American College of Rheumatology response of at least 50% (ACR50) at month 6 in the full analysis set (patients who were randomly assigned to a group and received at least one dose of the study treatment). Non-inferiority between groups was shown if the lower bound of the 98·34% CI of the difference between comparators was larger than -13·0%. This trial is registered with ClinicalTrials.gov, number NCT02187055. 1146 patients received treatment (384 had tofacitinib monotherapy; 376 had tofacitinib and methotrexate; and 386 had adalimumab and methotrexate). At 6 months, ACR50 response was attained in 147 (38%) of 384 patients with tofacitinib monotherapy, 173 (46%) of 376 patients with tofacitinib and methotrexate, and 169 (44%) of 386 patients with adalimumab and methotrexate. Non-inferiority was declared for tofacitinib and methotrexate versus adalimumab and methotrexate (difference 2% [98·34% CI -6 to 11]) but not for tofacitinib monotherapy versus either adalimumab and methotrexate (-6

Evidence-based recommendations for treatment with methotrexate in rheumatic disorders

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Madsen, Ole Rintek; Faurschou, Mikkel; Loft, Anne Gitte

2010-01-01

The aim of this study was to develop 3E (Evidence, Expertise, Exchange) recommendations (RCs) on the use of methotrexate in rheumatic disorders and to assess the agreement among Danish rheumatologists.......The aim of this study was to develop 3E (Evidence, Expertise, Exchange) recommendations (RCs) on the use of methotrexate in rheumatic disorders and to assess the agreement among Danish rheumatologists....

Importance of pharmacogenetic markers in the methylenetetrahydrofolate reductase gene during methotrexate treatment in pediatric patients with acute lymphoblastic leukemia

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Lazić Jelena

2017-01-01

Full Text Available Despite remarkable progress in survival of children with acute lymphoblastic leukemia (ALL which has reached about 85%, early toxicity and relapse rate remain issues that need to to be resolved. Genetic variants are important factors influencing the metabolism of cytotoxic drugs in ALL treatment. Variants in genes coding for methotrexate (MTX-metabolizing enzymes are under constant scientific interest due to their potential impact on drug toxicity and relapse rate. We investigated methylenetetrahydrofolate reductase (MTHFR c.677C>T and MTHFR c.1298A>C variants as pharmacogenetic markers of MTX toxicity and predictors of relapse. The study enrolled 161 children with ALL, treated according to the current International Berlin-Frankfurt-Munster group (BFM for diagnostics and treatment of leukemia and lymphoma protocols. Genotyping was performed using PCRRFLP and allele-specific PCR assays. Our results revealed similar distributions of MTHFR c.677C>T and MTHFR c.1298A>C genotypes among 104 healthy individuals as compared to pediatric ALL patients. A lower incidence of early MTX toxicity was noted in the MTHFR c.677TT genotype (p=0.017, while MTHFR c.1298A>C genotypes were not associated with MTX toxicity. Carriers of any MTHFR c.677C>T and MTHFR c.1298A>C genotypes did not experience decreased overall survival (OAS or higher relapse rates. Genetic variants in the MTHFR gene are not involved in leukemogenesis in pediatric ALL. The presence of the MTHFR c.677TT genotype was recognized as a predictive factor for decreased MTX toxicity during the intensification phase of therapy. Neither MTHFR c.677C>T nor MTHFR c.1298A>C genotypes correlated with an increased number of toxic deaths or relapse rate. Our study emphasizes the importance of implementing pharmacogenetic markers in order to optimize pediatric ALL therapy. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. III 41004

Methotrexate for refractory prurigo nodularis

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Mariam Al Zaabi

2017-01-01

Full Text Available Prurigo nodularis (PN is chronic unbearable inflammatory skin disease. Although it was described before a century, not many studies have been conducted regarding the systemic treatment of prurigo nodularis. A 64-year-old male patient has moderate to severe atopic dermatitis superimposed by disseminated pruritic nodules over the trunk and extremities. In spite of topical treatment and Phototherapy, patient condition was deteriorating. Therefore, the patient was treated with multimodalities including high potency topical steroid, intravenous antihistamine, cyclosporine and omalizumab without improvement. Thus the patient has been treated with methotrexate which led to remarkable improvement. Management of prurigo nodularis is often challenging as the etiology of PN in the majority of the cases is unknown. Conservative treatments are often inefficient. This case proves the efficacy of methotrexate in the management of prurigo nodularis.

Extended duration of prehydration does not prevent nephrotoxicity or delayed drug elimination in high-dose methotrexate infusions

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Mikkelsen, Torben Stamm; Mamoudou, Aissata Diop; Tuckuviene, Ruta

2014-01-01

Alkalized hydration is used as supportive care to prevent renal toxicity during infusions with high-dose methotrexate (HDMTX). In children with acute lymphoblastic leukemia (ALL), the hydration is commonly initiated 4 hours before start of the methotrexate (MTX) infusion. To test if longer durati...

Use of methotrexate in patients with uveitis.

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Ali, A; Rosenbaum, J T

2010-01-01

Methotrexate has been frequently employed to treat ocular inflammatory diseases including uveitis, scleritis, and orbital inflammatory disease. It is effective for intraocular lymphoma when given directly into the eye. No study has assessed its efficacy for eye disease in a randomised, placebo controlled design. This report reviews the literature relevant to methotrexate's utility in the treatment of ocular inflammatory disease.

Association between SLC19A1 gene polymorphism and high dose methotrexate toxicity in childhood acute lymphoblastic leukaemia and non Hodgkin malignant lymphoma: introducing a haplotype based approach

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Kotnik Barbara Faganel

2017-09-01

Full Text Available We investigated the clinical relevance of SLC 19A1 genetic variability for high dose methotrexate (HD-MTX related toxicities in children and adolescents with acute lymphoblastic leukaemia (ALL and non Hodgkin malignant lymphoma (NHML.

Is high dose methotrexate without irradiation of the brain sufficiently effective in prevention of CNS disease in children with acute lymphoblastic leukemia?

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Cap, J.; Foltinova, A.; Kaiserova, E.; Mojzesova, A.; Sejnova, D.; Jamarik, M.

1998-01-01

We present 5-year results of treatment in 93 children suffering from acute lymphoblastic leukemia using two therapeutic protocols containing multidrug chemotherapy including high dose methotrexate. We could ascertain different results in standard and high risk patients. In a group of 62 children with standard risk we observed improvement in complete remission rate being 98.9% after induction phase of therapy, only one patient died on septicemia. Relapse rate in this group was 21.2% and that 14. 7% in the bone marrow and 6.5% in CNS and no testicular relapse at all. In the group of 31 children with high risk leukemia all patients achieved complete remission. Only one of them died on acute pancreatitis due to toxicity. Overall relapse rate in this group was 28.9% with 12.8% of medullary relapse and 16.1 % of CNS relapse. The last one was significantly higher than in the previous study when brain irradiation was a part of therapeutic procedure. It seems that this treatment is effective mainly in the standard risk leukemia, however, in the high risk leukemias this procedure appears to be less effective in preventing CNS leukemia. In this group of patients irradiation of the brain need to be enclosed in the therapy. (authors)

Mercaptopurine/Methotrexate Maintenance Therapy of Childhood Acute Lymphoblastic Leukemia: Clinical Facts and Fiction

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Nielsen, Stine N.; Frandsen, Thomas L.; Nersting, Jacob

2014-01-01

The antileukemic mechanisms of 6-mercaptopurine (6MP) and methotrexate (MTX) maintenance therapy are poorly understood, but the benefits of several years of myelosuppressive maintenance therapy for acute lymphoblastic leukemia are well proven. Currently, there is no international consensus on drug dosing. Because of significant interindividual and intraindividual variations in drug disposition and pharmacodynamics, vigorous dose adjustments are needed to obtain a target degree of myelosuppression. As the normal white blood cell counts vary by patients’ ages and ethnicity, and also within age groups, identical white blood cell levels for 2 patients may not reflect the same treatment intensity. Measurements of intracellular levels of cytotoxic metabolites of 6MP and MTX can identify nonadherent patients, but therapeutic target levels remains to be established. A rise in serum aminotransferase levels during maintenance therapy is common and often related to high levels of methylated 6MP metabolites. However, except for episodes of hypoglycemia, serious liver dysfunction is rare, the risk of permanent liver damage is low, and aminotransferase levels usually normalize within a few weeks after discontinuation of therapy. 6MP and MTX dose increments should lead to either leukopenia or a rise in aminotransferases, and if neither is experienced, poor treatment adherence should be considered. The many genetic polymorphisms that determine 6MP and MTX disposition, efficacy, and toxicity have precluded implementation of pharmacogenomics into treatment, the sole exception being dramatic 6MP dose reductions in patients who are homozygous deficient for thiopurine methyltransferase, the enzyme that methylates 6MP and several of its metabolites. In conclusion, maintenance therapy is as important as the more intensive and toxic earlier treatment phases, and often more challenging. Ongoing research address the applicability of drug metabolite measurements for dose adjustments

COMPARATIVE EVALUATION OF THE EFFICACY AND SAFETY OF TREATMENT USING ADALIMUMAB IN COMBINATION WITH METHOTREXATE AND METHOTREXATE MONOTHERAPY IN CHILDREN WITH POLYARTICULAR JUVENILE IDIOPATHIC ARTHRITIS IN COMBINATION WITH UVEITIS

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V. А. Kel’tsev

2014-01-01

Full Text Available Juvenile idiopathic arthritis (JIA is the most common rheumatic disease in children and it is characterized by a primary lesion of the joints, organs and tissues with the formation of multiple organ failure of varying severity. The article describes the results of studying the efficacy and safety of adalimumab in combination with methotrexate (n = 26 and methotrexate monotherapy (n = 17 when treating the patients with polyarticular JIA and uveitis refractory to the basic immunosuppressive therapy. It was shown that the combination therapy induced the remission of arthritis in children with JIA in a shorter period of time. After 1 year, the disease remission was recorded in 42% of children in the treatment group and in 18% of children in the comparison group, the uveitis remission — in 26 (54% of 48 eyes and 2 (7% of 28 eyes with signs of lesions, respectively. It should be noted that adalimumab in combination with methotrexate was well tolerated and no serious adverse effects were recorded. Thus, the introduction of adalimumab in the treatment regimen of children with JIA and uveitis refractory to the basic immunosuppressive therapy allowed for the rapid disease remission while preserving the effect in a significant number of patients during the following year.

Effect of infliximab on renal injury due to methotrexate in rat.

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Kirbas, Aynur; Cure, Medine Cumhur; Kalkan, Yildiray; Cure, Erkan; Tumkaya, Levent; Sahin, Osman Zikrullah; Yuce, Suleyman; Kizilkaya, Bayram; Pergel, Ahmet

2015-05-01

Methotrexate, an antagonist of folic acid used in the treatment of many cancers and inflammatory diseases, is associated with side effects that limit its usage. Infliximab has been reported to have a protective effect against nephrotoxicity induced by some drugs and ischemic reperfusion. We aimed to investigate whether infliximab has a protective effect against methotrexate-induced nephrotoxicity. We administered methotrexate at a dose of 20 mg/kg as a single intraperitoneal injection in 10 rats (methotrexate group). Another group of 10 rats received a single dose of infliximab, 7 mg/kg, intraperitoneally (infliximab group). The methotrexate and infliximab group received a similar single injection of infliximab 72 hours prior to methotrexate injection. After 72 hours a single dose of methotrexate, 20 mg/kg, was administered intraperitoneally. Five days after methotrexate injection, blood samples were collected and the kidney tissues were removed for biochemical and histological examination. The methotrexate group had significantly higher tissue levels of tumor necrosis factor-α (P = .008), interleukin-1β (P = .04), nitric oxide (P < .001), and adenosine deaminase (P < .001) than the methotrexate and infliximab group after the 5-day study. The methotrexate group also had significantly higher total histological scores (P < .001) and carbonic anhydrase-II activity (P < .001) when compared to the methotrexate and infliximab group. Infliximab has a strong protective effect against methotrexate-induced nephrotoxicity by suppressing cytokines release. It may decrease methotrexate-induced nephrotoxicity by regulating carbonic anhydrase-II enzyme activities and slowing down purine metabolism.

Non-infectious chemotherapy-associated acute toxicities during childhood acute lymphoblastic leukemia therapy

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Schmiegelow, Kjeld; Müller, Klaus Gottlob; Mogensen, Signe Sloth

2017-01-01

During chemotherapy for childhood acute lymphoblastic leukemia, all organs can be affected by severe acute side effects, the most common being opportunistic infections, mucositis, central or peripheral neuropathy (or both), bone toxicities (including osteonecrosis), thromboembolism, sinusoidal...... useful risk factors, and across study groups there has been wide diversity in toxicity definitions, capture strategies, and reporting, thus hampering meaningful comparisons of toxicity incidences for different leukemia protocols. Since treatment of acute lymphoblastic leukemia now yields 5-year overall...... obstruction syndrome, endocrinopathies (especially steroid-induced adrenal insufficiency and hyperglycemia), high-dose methotrexate-induced nephrotoxicity, asparaginase-associated hypersensitivity, pancreatitis, and hyperlipidemia. Few of the non-infectious acute toxicities are associated with clinically...

A randomized study of the prevention of acute graft-versus-host disease

International Nuclear Information System (INIS)

Ramsay, N.K.C.; Kersey, J.H.; Robison, L.L.; McGlave, P.B.; Woods, W.G.; Krivit, W.; Kim, T.H.; Goldman, A.I.; Nesbit, M.E. Jr.

1982-01-01

Acute graft-versus-host disease is a major problem in allogeneic bone-marrow transplantation. We performed a randomized study to compare the effectiveness of two regimens in the prevention of acute graft-versus-host disease. Thirty-five patients received methotrexate alone, and 32 received methotrexate, antithymocyte globulin, and prednisone. Of the patients who received methotrexate alone, 48 percent had acute graft-versus-host disease, as compared with 21 per cent of those who received methotrexate, antithymocyte globulin, and prednisone (P = 0.01). The age of the recipient was a significant factor in the development of acute graft-versus-host disease: Older patients had a higher incidence of the disease (P = 0.001). We conclude that the combination of methotrexate, antithymocyte globulin, and prednisone significantly decreased the incidence of acute graft-versus-host disease and should be used to prevent this disorder in patients receiving allogeneic marrow transplants

Methotrexate/6-mercaptopurine maintenance therapy influences the risk of a second malignant neoplasm after childhood acute lymphoblastic leukemia: results from the NOPHO ALL-92 study

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Schmiegelow, Kjeld; Al-Modhwahi, Ibrahim; Andersen, Mette Klarskov

2009-01-01

Among 1614 children with acute lymphoblastic leukemia (ALL) treated with the Nordic Society for Paediatric Haematology and Oncology (NOPHO) ALL-92 protocol, 20 patients developed a second malignant neoplasm (SMN) with a cumulative risk of 1.6% at 12 years from the diagnosis of ALL. Nine of the 16...... acute myeloid leukemias or myelodysplastic syndromes had monosomy 7 (n = 7) or 7q deletions (n = 2). In Cox multivariate analysis, longer duration of oral 6-mercaptopurine (6MP)/methotrexate (MTX) maintenance therapy (P = .02; longest for standard-risk patients) and presence of high hyperdiploidy (P...

A randomized clinical trial comparing methotrexate and mycophenolate mofetil for noninfectious uveitis.

Science.gov (United States)

Rathinam, Sivakumar R; Babu, Manohar; Thundikandy, Radhika; Kanakath, Anuradha; Nardone, Natalie; Esterberg, Elizabeth; Lee, Salena M; Enanoria, Wayne T A; Porco, Travis C; Browne, Erica N; Weinrib, Rachel; Acharya, Nisha R

2014-10-01

To compare the relative effectiveness of methotrexate and mycophenolate mofetil for noninfectious intermediate uveitis, posterior uveitis, or panuveitis. Multicenter, block-randomized, observer-masked clinical trial. Eighty patients with noninfectious intermediate, posterior, or panuveitis requiring corticosteroid-sparing therapy at Aravind Eye Hospitals in Madurai and Coimbatore, India. Patients were randomized to receive 25 mg weekly oral methotrexate or 1 g twice daily oral mycophenolate mofetil and were monitored monthly for 6 months. Oral prednisone and topical corticosteroids were tapered. Masked examiners assessed the primary outcome of treatment success, defined by achieving the following at 5 and 6 months: (1) ≤0.5+ anterior chamber cells, ≤0.5+ vitreous cells, ≤0.5+ vitreous haze and no active retinal/choroidal lesions in both eyes, (2) ≤10 mg of prednisone and ≤2 drops of prednisolone acetate 1% a day, and (3) no declaration of treatment failure because of intolerability or safety. Additional outcomes included time to sustained corticosteroid-sparing control of inflammation, change in best spectacle-corrected visual acuity, resolution of macular edema, adverse events, subgroup analysis by anatomic location, and medication adherence. Forty-one patients were randomized to methotrexate and 39 to mycophenolate mofetil. A total of 67 patients (35 methotrexate, 32 mycophenolate mofetil) contributed to the primary outcome. Sixty-nine percent of patients achieved treatment success with methotrexate and 47% with mycophenolate mofetil (P = 0.09). Treatment failure from adverse events or tolerability was not different by treatment arm (P = 0.99). There were no differences between treatment groups in time to corticosteroid-sparing control of inflammation (P = 0.44), change in best spectacle-corrected visual acuity (P = 0.68), or resolution of macular edema (P = 0.31). There was no statistically significant difference in corticosteroid-sparing control of

A Combination of Surgery And Methotrexate for Successful Treatment of a Caesarean Scar Ectopic Pregnancy.

LENUS (Irish Health Repository)

Tadesse, WG

2018-06-01

Caesarean scar ectopic pregnancy (CSEP) is one of the rarest forms of ectopic pregnancies. With rising caesarean delivery (CD) rates worldwide, there is an increase in the incidence of CSEP. Patients usually present with painless vaginal bleeding and often misdiagnosed as spontaneous miscarriage. The use of ultrasonography with colour flow Doppler helps in the differential diagnosis. Different treatment options are described in the literature, although there is insufficient evidence regarding the best approach. We report the diagnosis and management of a case of CSEP in a woman with four previous CD who presented with vaginal bleeding and lower abdominal cramps at six weeks of gestation. She was treated with laparoscopic and ultrasound guided aspiration of the gestational sac and local injection of methotrexate supplemented by intramuscular methotrexate injection.

Efficacy of etanercept in preventing relapse of uveitis controlled by methotrexate.

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Foster, C Stephen; Tufail, Fehma; Waheed, Nadia Khalida; Chu, David; Miserocchi, Elisabetta; Baltatzis, Stefanos; Vredeveld, Cindy M

2003-04-01

To evaluate the efficacy of etanercept vs placebo in preventing relapses of uveitis in patients taking methotrexate with control of uveitis and whose methotrexate dosage was being tapered. Patients with chronic or recurrent noninfectious uveitis with inflammation controlled by low-dose methotrexate were randomized to either the drug or placebo group in a double-masked manner, given a methotrexate taper schedule, and followed for 24 weeks. The main outcome measures were control of inflammation, visual acuity, and adverse reactions. Data were analyzed both as an attempt-to-treat analysis and an analysis only of those patients who completed the study. A total of 20 patients were randomized to the drug and placebo groups. Relapse of uveitis occurred in 3 of 10 patients in the treatment group and 5 of 10 patients in the control group. Two patients in the treatment group withdrew prematurely from the study due to adverse effects. There was no significant difference between the treatment and placebo groups with regard to the rate of relapse and the final visual acuity. No patient suffered from any irreversible, long-term morbidity or mortality. Etanercept has no significant efficacy over placebo in preventing relapses of uveitis in patients being tapered from methotrexate.

Pancytopenia associated with low-dose methotrexate therapy – case reports

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Marija Čeh

2012-12-01

Conclusions: With the increasing long-term use of methotrexate, it is important that patients should be monitored during treatment for haematological side-effects, as pancytopenia can be a late manifestation. Furthermore, more attention should be paid to risk factors predisposing hematological toxicity of methotrexate before commencing this drug

CT and MRI appearances of methotrexate leucoencephalopathy

International Nuclear Information System (INIS)

Wilks, M.J.; Tie, M.L.K.; Pozza, C.H.

2002-01-01

Methotrexate is a well recognised cause of diffuse symmetrical leucoencephalopathy. The widespread use of the drug in chemotherapeutic regimes necessitates awareness of this complication. A case report and a brief literature review is presented. A 20-year-old single woman presented to the Emergency Department with a 6-week history of general malaise, lower back pain and a petechial rash. From investigations including blood picture and bone marrow trephine, the diagnosis of acute lymphoblastic leukaemia (ALL) was made. Three cycles of induction chemotherapy were administered consisting of intravenous cytarabine and hydrocortisone and intrathecal methotrexate. Shortly after the third cycle of induction chemotherapy (6 weeks following diagnosis, 2 days following the last dose of intrathecal methotrexate) she presented with an acute neurological episode consisting of muteness and somnolence. Physical examination showed generalised flaccidity to all muscle groups and generalised loss of reflexes. There were no consistent cranial neuropathies and the patient was not neutropenic. Computed tomography of the brain showed extensive symmetric white matter hypodensity extending throughout the corona radiata and deep white matter tracts especially the external capsules. There was no abnormal enhancement with non-ionic contrast administration or evidence of grey matter involvement. Magnetic resonance imaging was subsequently performed, the fluid attenuated inversion recovery images (FLAIR) and T2-weighted image (T2WI) demonstrated marked white matter hyperintensity; the involvement was more extensive than demonstrated on the CT with additional involvement of the subcortical and cerebellar white matter, the basal ganglia and cortex of the mesial temporal and inferior frontal lobes. Gadolinium was not administered. A follow up study after 4 weeks of steroid and folinic acid therapy showed complete resolution of the white matter hyperintensity on the T2WI and FLAIR sequences

A Randomized Clinical Trial Comparing Methotrexate and Mycophenolate Mofetil for Non-Infectious Uveitis

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Rathinam, Sivakumar R; Babu, Manohar; Thundikandy, Radhika; Kanakath, Anuradha; Nardone, Natalie; Esterberg, Elizabeth; Lee, Salena M; Enanoria, Wayne TA; Porco, Travis C; Browne, Erica N; Weinrib, Rachel; Acharya, Nisha R

2014-01-01

Objective To compare the relative effectiveness of methotrexate and mycophenolate mofetil for non-infectious intermediate uveitis, posterior uveitis, or panuveitis. Design Multicenter, block-randomized, observer-masked clinical trial Participants Eighty patients with non-infectious intermediate, posterior or panuveitis requiring corticosteroid-sparing therapy at Aravind Eye Hospitals in Madurai and Coimbatore, India. Intervention Patients were randomized to receive 25mg weekly oral methotrexate or 1g twice daily oral mycophenolate mofetil and were monitored monthly for 6 months. Oral prednisone and topical corticosteroids were tapered. Main Outcome Measures Masked examiners assessed the primary outcome of treatment success, defined by achieving the following at 5 and 6 months: (1) ≤0.5+ anterior chamber cells, ≤0.5+ vitreous cells, ≤0.5+ vitreous haze and no active retinal/choroidal lesions in both eyes, (2) ≤ 10 mg of prednisone and ≤ 2 drops of prednisolone acetate 1% a day and (3) no declaration of treatment failure due to intolerability or safety. Additional outcomes included time to sustained corticosteroid-sparing control of inflammation, change in best spectacle-corrected visual acuity, resolution of macular edema, adverse events, subgroup analysis by anatomic location, and medication adherence. Results Forty-one patients were randomized to methotrexate and 39 to mycophenolate mofetil. A total of 67 patients (35 methotrexate, 32 mycophenolate mofetil) contributed to the primary outcome. Sixty-nine percent of patients achieved treatment success with methotrexate and 47% with mycophenolate mofetil (p=0.09). Treatment failure due to adverse events or tolerability was not significantly different by treatment arm (p=0.99). There were no statistically significant differences between treatment groups in time to corticosteroid-sparing control of inflammation (p=0.44), change in best spectacle-corrected visual acuity (p=0.68), and resolution of macular

Systematic review and meta-analysis of the efficacy and safety of leflunomide and methotrexate in the treatment of rheumatoid arthritis.

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Alfaro-Lara, Roberto; Espinosa-Ortega, Hector Fabricio; Arce-Salinas, César Alejandro

2017-08-31

To assess the efficacy and side effects of methotrexate and leflunomide in patients with rheumatoid arthritis (RA) as the first disease-modifying antirheumatic drug (DMARD). We performed a systematic review and meta-analysis of clinical studies that included patients who took methotrexate, leflunomide, placebo or another DMARD for RA treatment. A systematic review yielded 1971 articles from databases; once completely reviewed, 73 trials that completed inclusion criteria were selected. In structured workshops for discussion and assessment of each article, 6 could be meta-analyzed for the primary and secondary outcomes: achievement of American College of Rheumatology (ACR) 20 and its core set components; and change of serum C-reactive protein (CRP) levels, Health Assessment Questionnaire Disability Index (HAQ-Di), liver enzyme aspartate transaminase/alanine transaminase ratio, new gastrointestinal (GI) side effects and infections. A total of 1984 patients were included: 986 took leflunomide and 998 methotrexate. The probability of achieving ACR 20 had an odds ratio (OR) of 0.88 (95% confidence interval [CI] 0.74, 1.06) with a trend toward favoring methotrexate; reduction of the swollen joint count was greater for methotrexate: mean difference=0.82 (95%CI 0.24, 1.39); tender joint count, physician global assessment, HAQ-Di, and serum CRP levels revealed no significant difference between groups. Increased liver enzymes were more frequent in the leflunomide group, OR=0.38 (95%CI 0.27, 0.53), and new GI complaints were more common with methotrexate (OR=1.44; 95%CI 1.17, 1.79). There was no difference in the incidence of non-severe infections. Leflunomide used as the first DMARD in RA seemed to be as efficacious as methotrexate; only the reduction of swollen joint count was more marked for methotrexate. Leflunomide was linked to a greater increase in liver enzymes, but there were fewer GI complaints. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de

Pharmacogenetic markers to predict the clinical response to methotrexate in south Indian Tamil patients with psoriasis.

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Indhumathi, S; Rajappa, Medha; Chandrashekar, Laxmisha; Ananthanarayanan, P H; Thappa, D M; Negi, V S

2017-08-01

Despite the advent of several new systemic therapies, methotrexate remains the gold standard for the treatment of moderate to severe psoriasis. However, there exists a significant heterogeneity in individual response to methotrexate. There are no consistently reliable markers to predict methotrexate treatment response till date. We aimed to demonstrate the association of certain genetic variants in the HLA (HLA-A2, HLA-B17, and HLA-Cw6) and the non-HLA genes including T-helper (Th)-1, Th-2, Th-17 cytokine genes (IFN-γ, IL-2, IL-4, IL-10, IL-12B, and IL-23R), and T-regulatory gene (FOXP3) with the methotrexate treatment response in South Indian Tamil patients with psoriasis. Of the 360 patients recruited, 189 patients with moderate to severe psoriasis were treated with methotrexate. Of the 189 patients, 132 patients responded to methotrexate and the remaining 57 patients were non-responders. We analyzed the association of aforesaid polymorphisms with the methotrexate treatment outcome using binary logistic regression. We observed that there were significant differences between genotype frequencies of HLA-Cw6 and FOXP3 (rs3761548) among the responders compared to non-responders, with conservative estimation. We observed that pro-inflammatory cytokines such as IFN-γ, IL-2, IL-12, and IL-23 were markedly reduced with the use of methotrexate, in comparison to the baseline levels, while the plasma IL-4 levels were increased posttreatment. Our results serve as preliminary evidence for the clinical use of genetic markers as predictors of response to methotrexate in psoriasis. This might aid in the future in the development of a point-of-care testing (POCT) gene chip, to predict optimal treatment response in patients with psoriasis, based on their individual genotypic profile.

Hepatotoxicity During Maintenance Therapy and Prognosis in Children With Acute Lymphoblastic Leukemia

DEFF Research Database (Denmark)

Ebbesen, Maria S.; Nygaard, Ulrikka; Rosthøj, Susanne

2017-01-01

Hepatotoxicity is a known toxicity to treatment of childhood acute lymphoblastic leukemia. Hepatotoxicity occurs during maintenance therapy and is caused by metabolites of 6-Mercaptopurine (6 MP) and Methotrexate (MTX). Our objective was to investigate the association between alanine...

Methotrexate: Revisited efficiency and safety of drug administration in psoriasis patients

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A. L. Bakulev

2017-01-01

Full Text Available The article presents the current data of the literature on methotrexate, which is now one of the most commonly used preparation for the systemic treatment of patients with moderate to severe psoriasis. The following problems are under consideration: estimation by specialists of response to systemic psoriasis therapy and possible therapeutic strategies; selecting initial doses of methotrexate for the treatment of patients with psoriasis; the possibilities of combined use with genetically engineered biological agents and monitoring of therapy. The data from randomized clinical trials on the long-term continuous treatment with methotrexate (efficacy, safety; methods of its administration to patients and time and criteria for long-term effecasy are reported. There are presented the data on the mechanisms of methotrexate action and the new data about the impact on the adenosine metabolism and the ability of the preparation to modulate the inflammatory response in the skin of patients by inhibiting the cellular components of the inflammatory infiltrate in the skin (dendritic antigen-producing cells and T-lymphocytes, as well as the suppression of expression of some proinflammatory cytokines (IFN-y and IL17A.

Methotrexate as a first-line corticosteroid-sparing therapy in a cohort of uveitis and scleritis.

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Kaplan-Messas, Audrey; Barkana, Yaniv; Avni, Isaac; Neumann, Ron

2003-06-01

To evaluate the clinical experience with methotrexate as a first-line corticosteroid-sparing drug in patients with resistant ocular inflammation. We retrospectively studied 39 consecutive patients with uveitis (n = 36) or scleritis (n = 3) who were treated with methotrexate following inadequate control with corticosteroids lasting five years. Criteria for initiating treatment with methotrexate and defining outcome were strictly defined. The cohort included 21 females and 18 males, all Caucasians, with a mean age of 26.6 years (range: 3-73 years). Patients were followed up for 21.5 +/- 12.6 months. Treatment was discontinued due to side effects in 10 patients (26%). Of the remaining 29 patients, full or partial control of inflammation was achieved in 23 (79%). Response to treatment was observed after a mean of 2.4 +/- 0.8 months. Ten patients were fully controlled and discontinued methotrexate therapy after a mean of 20.9 +/- 9.2 months, with no recurrence of inflammation. Use of topical and systemic corticosteroids was markedly reduced in responsive patients. Methotrexate is recommended as a first-line adjunct to or replacement of systemic corticosteroids in the treatment of ocular inflammation.

Liposomal Cytarabine Induces Less Neurocognitive Dysfunction Than Intrathecal Methotrexate in an Animal Model

DEFF Research Database (Denmark)

Thomsen, Anna M; Gulinello, Maria E; Wen, Jing

2018-01-01

Liposomal cytarabine is currently being tested clinically as an alternative to intrathecal (IT) methotrexate (MTX) for preventing relapse within the central nervous system among patients with acute lymphoblastic leukemia. To compare the toxicity and cognitive deficits caused by IT MTX versus lipo...

Successful treatment of methotrexate intolerance in juvenile idiopathic arthritis using eye movement desensitization and reprocessing - treatment protocol and preliminary results.

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Höfel, Lea; Eppler, Bruno; Storf, Magdalena; Schnöbel-Müller, Elizabeth; Haas, Johannes-Peter; Hügle, Boris

2018-02-13

Methotrexate (MTX), commonly used in juvenile idiopathic arthritis (JIA), frequently has to be discontinued due to intolerance with anticipatory and associative gastrointestinal adverse effects. Eye Movement Desensitization and Reprocessing (EMDR) is a psychological method where dysfunctional experiences and memories are reprocessed by recall combined with bilateral eye movements. The objective of this study was to assess efficacy of EMDR for treatment of MTX intolerance in JIA patients. We performed an open prospective study on consecutive JIA patients with MTX intolerance. Intolerance was determined using the Methotrexate Intolerance Severity Score (MISS) questionnaire prior to treatment, directly after treatment and after four months. Health-related quality of life was determined using the PedsQL prior to and four months after treatment. Patients were treated according to an institutional EMDR protocol with 8 sessions over two weeks. Changes in MISS and PedsQL were analyzed using non-parametric statistics. Eighteen patients with MTX intolerance (median MISS at inclusion 16.5, IQR = 11.75-20.25) were included. Directly after treatment, MTX intolerance symptoms were significantly improved (median MISS 1 (IQR = 0-2). After four months, median MISS score was at 6.5 (IQR = 2.75-12.25, p = 0.001), with 9/18 patients showing MISS scores ≥6. Median PedsQL after 4 months improved significantly from 77.6% to 85.3% (p = 0.008). MTX intolerance in children with JIA was effectively treated using an EMDR protocol, with lasting effect over a period of 4 months. EMDR treatment can potentially increase quality of life of affected patients and enable continued MTX treatment.

Evaluation of the Efficacy of Combined Therapy of Methotrexate and Etanercept versus Methotrexate as a Mono-Therapy.

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Rexhepi, Sylejman; Rexhepi, Mjellma; Rexhepi, Blerta; Sahatçiu-Meka, Vjollca; Mahmutaj, Vigan

2018-05-20

This study aims to evaluate the efficacy of Methotrexate (MTX) alone and combined therapy with Etanercept (ETN) and Methotrexate in patients with active rheumatoid arthritis (RA). In the randomised control study, conducted in the period from March 2014 until March 2016, we evaluated the efficacy of the treatment of patients with RA with MTX as monotherapy and combination treatment with MTX and ETN. In the Clinic of Rheumatology in Prishtina, 90 adult patients with RA were treated in combination with ETN (doses of 50 mg subcutaneously/weekly), with oral MTX (doses up to 20 mg weekly), and MTX alone (doses up to 20 mg weekly) during this period of two years. Clinical response was assessed using European League against Rheumatism (EULAR)/American College of Rheumatology (ACR) Criteria and the Disease Activity Score (DAS28). Radiographic changes were measured in the beginning and at the end of the study using Larsen's method. Of the cohort groups of 90 patients, mean age of 55.63, 15 patients, (16.6 %) were treated with combined therapy (ETN plus MTX) and 75 patients (83.3%) with monotherapy (MTX). After two years of treatment the group with combined therapy resulted with improvement of acute phase reactants as erythrocyte sedimentation rate (ESR) for the first hour (41.1 vs. 10.3 mm/hour) and C - reactive protein (CRP) (40.8 vs. 6 mg/liter), and compared to the group treated with monotherapy, there were no significant changes (ESR: 45.7 vs 34.3 mm/hour; CRP: 48 vs 24 mg/liter). Before the treatment, the severity of the disease was high, wherein the group with combined therapy DAS28 was 5.32, compared to the monotherapy group whom DAS28 was 5.90. After 2 years of treatment, we had significant changes in the results of DAS28, wherein the group treated with ETN plus MTX DAS28 was 2.12 ± 0.15, while in the group of patients treated with MTX DAS28 were 3.75 ± 0.39 (t = 13.03; df = 58; p < 0.0001). The group with combined therapy showed no evidence of radiographic

The combined application of biological therapy and methotrexate in case of escape phenomenon progressing

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Ponich E.S.

2015-09-01

Full Text Available Aim: the study of the efficacy of methotrexate in patients with the "escape effect" during the ustekinumab therapy. Materials and Methods. The results of methotrexate at a dose of 15-20mg/week in treatment of 4 patients receiving biologic and developed "escape effect". Ustekinumab is used as a hypodermic injection at a dose of 45 mg for a body weight of a patient no more than 100 kg, and 90 mg of body weight over 100 kg, at the zero week, the 4th week and then every 12 weeks. Patients control meets the standard management of patients in biological therapy. Results. The study shows that in the case of the resistance progressing when applying preparations of biological therapy, methotrexate is useful at a dose of 15-20mg/week for up to 6 months. The combined use of biologic therapy and methotrexate in the treatment of patients with psoriasis vulgaris, "escape effect" contributes to the marked regression of clinical symptoms and allows to control the process long enough, which is confirmed by the dynamics of the index PASI, BRS and DLQI. The combined method is highly safe, as evidenced by the lack of inhibition of hematopoiesis, the normal level of hepatic transaminases and serum creatinine, which greatly improves patient compliance in this type of therapy. Conclusion. The article presents the data of the combined application of biological medication therapy (ustekinumab and methotrexate for the treatment of patients with the common form of psoriasis vulgaris. In the case of the development of resistance of biological therapy recommended the appointment of methotrexate. The combined use of methotrexate and biologic therapy in the treatment of patients with psoriasis vulgaris contributes to marked regression of clinical symptoms and allows to control the process for a long time.

Experience of Parenteral Administration of Methotrexate in a Female Patient Suffering from Early Juvenile Idiopathic Arthritis and Uveitis

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Т. V. Sleptsova

2015-01-01

Full Text Available Represented here is a case of early juvenile idiopathic arthritis associated with uveitis diagnosed in a three-year-old female patient subject to treatment with the standard methotrexate dosage. At the initial stage of treatment, the child demonstrated severe articular syndrome, inflammatory reactions affecting eyeball surfaces, increased laboratory indicators of the illness and functional insufficiency. Successful overcoming of methotrexate resistance through dosage increased up to 20 mg/m2 of body surface per week was described. Over three months of subcutaneous methotrexate treatment with a 15 mg/m2-per-week dose, the child showed milder joint exudation an, arthralgia, less lengthy morning stiffness, although there was no 50% improvement based on ACRpedi criteria, and uveitis was first recognized in the subactive phase. The dose was increased up to 20 mg/m2 per week. By the eighth week of methotrexate treatment, uveal inflammation reversed. Non-active phase and remission were detected in 6 and 12 months respectively. The remission has persisted for 6 years. No side effects have been observed throughout methotrexate treatment. 

The optimal cutoff serum level of human chorionic gonadotropin for efficacy of methotrexate treatment in women with extrauterine pregnancy.

Science.gov (United States)

Sagiv, Ron; Debby, Abraham; Feit, Hagit; Cohen-Sacher, Bina; Keidar, Ran; Golan, Abraham

2012-02-01

To evaluate the efficacy of methotrexate treatment for extrauterine pregnancy and define criteria for prediction of success. Of 829 patients with an ectopic pregnancy admitted to E. Wolfson Medical Center, Holon, Israel, from January 1997 through December 2009, 238 had asymptomatic tubal pregnancies and increasing serum β-human chorionic gonadotropin (βhCG) levels. These patients were treated with a single intramuscular injection of 50mg of methotrexate (MTX) per square meter of body surface. Success was defined as undetectable βhCG levels without the need for a surgical intervention. The groups of patients successfully treated (n=167 [70%]) and unsuccessfully treated (n=71 [30%]) were compared. They were similar regarding age and gravidity. The initial serum βhCG level was significantly higher in the latter group than in the former (3798 mIU/mL vs. 1601 mIU/mL, Pinitial βhCG levels were less than 1000 mIU/mL, 71% when they were between 1000 and 2000 mIU/mL, and only 59% when they were between 2000 and 3000 mIU/mL. Methotrexate treatment is a safe and effective alternative to surgery. However, patients with initial βhCG levels higher than 2000 mIU/mL should only be offered the surgical approach. Copyright © 2011. Published by Elsevier Ireland Ltd.

Correlation of RAD51 and radiosensitization of methotrexate

International Nuclear Information System (INIS)

Du Liqing; Bai Jianqiang; Liu Qiang; Wang Yan; Zhao Peng; Chen Fenghua; Wang Hong; Fan Feiyue

2012-01-01

Objective: To evaluate the correlation between homologous recombination repair protein RAD51 and methotrexate-enhanced radiosensitivity. Methods: Western blot and RT-PCR assays were used to detect RAD51 expression in HOS osteosarcoma cells exposed to γ-ray irradiation alone and in combination with methotrexate. Colony formation assay was used to test the survival fraction of HOS cells exposed to γ-rays and methotrexate. Results: Methotrexate inhibited both protein and RNA expressions of RAD51, and the combination of radiation and methotrexate enhanced the inhibition of RAD51 expression. Moreover, transfection of cells with RAD51 gene decreased cellular sensitivity to methotrexate and γ-rays. The sensitizer enhancement ratios after irradiation in combination with methotrexate were 1.51 and 0.99, respectively. Methotrexate was a preferred radiosensitizer to HOS cell. Conclusions: RAD51 might be involved in the methotrexate-enhanced radiosensitivity. (authors)

Synthesis of protein-coated biocompatible methotrexate-loaded PLA-PEG-PLA nanoparticles for breast cancer treatment

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Salam Massadeh

2016-06-01

Full Text Available Background: PLA-PEG-PLA triblock polymer nanoparticles are promising tools for targeted dug delivery. The main aim in designing polymeric nanoparticles for drug delivery is achieving a controlled and targeted release of a specific drug at the therapeutically optimal rate and choosing a suitable preparation method to encapsulate the drug efficiently, which depends mainly on the nature of the drug (hydrophilic or hydrophobic. In this study, methotrexate (MTX-loaded nanoparticles were prepared by the double emulsion method. Method: Biodegradable polymer polyethylene glycol-polylactide acid tri-block was used with poly(vinyl alcohol as emulsifier. The resulting methotrexate polymer nanoparticles were coated with bovine serum albumin in order to improve their biocompatibility. This study focused on particle size distribution, zeta potential, encapsulation efficiency, loading capacity, and in vitro drug release at various concentrations of PVA (0.5%, 1%, 2%, and 3%. Results: Reduced particle size of methotrexate-loaded nanoparticles was obtained using lower PVA concentrations. Enhanced encapsulation efficiency and loading capacity was obtained using 1% PVA. FT-IR characterization was conducted for the void polymer nanoparticles and for drug-loaded nanoparticles with methotrexate, and the protein-coated nanoparticles in solid state showed the structure of the plain PEG-PLA and the drug-loaded nanoparticles with methotrexate. The methotrexate-loaded PLA-PEG-PLA nanoparticles have been studied in vitro; the drug release, drug loading, and yield are reported. Conclusion: The drug release profile was monitored over a period of 168 hours, and was free of burst effect before the protein coating. The results obtained from this work are promising; this work can be taken further to develop MTX based therapies.

Synthesis of protein-coated biocompatible methotrexate-loaded PLA-PEG-PLA nanoparticles for breast cancer treatment

Science.gov (United States)

Massadeh, Salam; Alaamery, Manal; Al-Qatanani, Shatha; Alarifi, Saqer; Bawazeer, Shahad; Alyafee, Yusra

2016-01-01

Background PLA-PEG-PLA triblock polymer nanoparticles are promising tools for targeted dug delivery. The main aim in designing polymeric nanoparticles for drug delivery is achieving a controlled and targeted release of a specific drug at the therapeutically optimal rate and choosing a suitable preparation method to encapsulate the drug efficiently, which depends mainly on the nature of the drug (hydrophilic or hydrophobic). In this study, methotrexate (MTX)-loaded nanoparticles were prepared by the double emulsion method. Method Biodegradable polymer polyethylene glycol-polylactide acid tri-block was used with poly(vinyl alcohol) as emulsifier. The resulting methotrexate polymer nanoparticles were coated with bovine serum albumin in order to improve their biocompatibility. This study focused on particle size distribution, zeta potential, encapsulation efficiency, loading capacity, and in vitro drug release at various concentrations of PVA (0.5%, 1%, 2%, and 3%). Results Reduced particle size of methotrexate-loaded nanoparticles was obtained using lower PVA concentrations. Enhanced encapsulation efficiency and loading capacity was obtained using 1% PVA. FT-IR characterization was conducted for the void polymer nanoparticles and for drug-loaded nanoparticles with methotrexate, and the protein-coated nanoparticles in solid state showed the structure of the plain PEG-PLA and the drug-loaded nanoparticles with methotrexate. The methotrexate-loaded PLA-PEG-PLA nanoparticles have been studied in vitro; the drug release, drug loading, and yield are reported. Conclusion The drug release profile was monitored over a period of 168 hours, and was free of burst effect before the protein coating. The results obtained from this work are promising; this work can be taken further to develop MTX based therapies.

Non-infectious chemotherapy-associated acute toxicities during childhood acute lymphoblastic leukemia therapy

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Schmiegelow, Kjeld; Müller, Klaus; Mogensen, Signe Sloth; Mogensen, Pernille Rudebeck; Wolthers, Benjamin Ole; Stoltze, Ulrik Kristoffer; Tuckuviene, Ruta; Frandsen, Thomas

2017-01-01

During chemotherapy for childhood acute lymphoblastic leukemia, all organs can be affected by severe acute side effects, the most common being opportunistic infections, mucositis, central or peripheral neuropathy (or both), bone toxicities (including osteonecrosis), thromboembolism, sinusoidal obstruction syndrome, endocrinopathies (especially steroid-induced adrenal insufficiency and hyperglycemia), high-dose methotrexate-induced nephrotoxicity, asparaginase-associated hypersensitivity, pancreatitis, and hyperlipidemia. Few of the non-infectious acute toxicities are associated with clinically useful risk factors, and across study groups there has been wide diversity in toxicity definitions, capture strategies, and reporting, thus hampering meaningful comparisons of toxicity incidences for different leukemia protocols. Since treatment of acute lymphoblastic leukemia now yields 5-year overall survival rates above 90%, there is a need for strategies for assessing the burden of toxicities in the overall evaluation of anti-leukemic therapy programs. PMID:28413626

Individualized toxicity-titrated 6-mercaptopurine increments during high-dose methotrexate consolidation treatment of lower risk childhood acute lymphoblastic leukaemia. A Nordic Society of Paediatric Haematology and Oncology (NOPHO) pilot study

DEFF Research Database (Denmark)

Frandsen, Thomas L; Abrahamsson, Jonas; Lausen, Birgitte

2011-01-01

This study explored the feasibility and toxicity of individualized toxicity-titrated 6-mercaptopurine (6MP) dose increments during post-remission treatment with High-dose methotrexate (HDM) (5000 mg/m(2), ×3) in 38 patients with Childhood (ALL). Patients were increased in steps of 25 mg 6MP/m(2...... the remaining patients (P = 0·03). This study shows individualized toxicity-titrated 6MP dosing during consolidation is feasible without increased risk of toxicity....

Methotrexate therapy for chronic noninfectious uveitis: analysis of a case series of 160 patients.

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Samson, C M; Waheed, N; Baltatzis, S; Foster, C S

2001-06-01

To evaluate the outcomes of patients with chronic noninfectious uveitis unresponsive to conventional antiinflammatory therapy who were treated with methotrexate. Retrospective noncomparative interventional case series. All patients with chronic noninfectious uveitis treated with methotrexate at a single institution from 1985 to 1999. Charts of patients seen on the Ocular Immunology & Uveitis Service at the Massachusetts Eye & Ear Infirmary were reviewed. Patients with chronic uveitis of noninfectious origin treated with methotrexate were included in the study. Control of inflammation, steroid-sparing effect, visual acuity, adverse reactions. A total of 160 patients met the inclusion criteria. Control of inflammation was achieved in 76.2% of patients. Steroid-sparing effect was achieved in 56% of patients. Visual acuity was maintained or improved in 90% of patients. Side effects requiring discontinuation of medication occurred in 18% of patients. Potentially serious adverse reactions occurred in only 8.1% of patients. There was neither long-term morbidity nor mortality caused by methotrexate. Methotrexate is effective in the treatment of chronic noninfectious uveitis that fails to respond to conventional steroid treatment. It is an effective steroid-sparing immunomodulator, is a safe medication, and is well tolerated.

Methotrexate treatment provokes apoptosis of proliferating keratinocyte in psoriasis patients.

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Elango, Tamilselvi; Thirupathi, Anand; Subramanian, Swapna; Ethiraj, Purushoth; Dayalan, Haripriya; Gnanaraj, Pushpa

2017-08-01

Psoriasis is a chronic inflammatory skin disease characterized by hyper proliferation of keratinocytes. Recent data show that the epidermis thickening in psoriasis may be related to imbalance of homeostasis caused by abnormal apoptotic process. Maintenance of keratinocyte apoptotic process is very important in psoriasis. Methotrexate (MTX) has been used for many years to restore the normal skin in psoriasis condition. However, the exact mechanism of MTX in psoriasis condition is poorly understood. The aim of this study was to examine the role of MTX on keratinocyte apoptosis pathway in psoriasis patients. A total of 58 psoriasis vulgaris patients were recruited for this study. Nonlesional skin biopsies served as control. Skin biopsies of psoriatic patients were collected and analyzed for cytosolic, mitochondria and total cytochrome c by ELISA. Expression of caspase-9, NFκBp65, pAkt1 by western blot, real-time PCR and immunohistochemical analysis of c-FLIP protein was analyzed in nonlesional and lesional skin biopsies before (day 0) and after (at the end of 6 and 12 weeks) MTX treatment. After MTX treatment, a significant increase in cytochrome c was observed when compared with before MTX treatment in psoriasis patients (p psoriasis by controlling the acanthosis.

Acute Central Nervous System Complications in Pediatric Acute Lymphoblastic Leukemia.

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Baytan, Birol; Evim, Melike Sezgin; Güler, Salih; Güneş, Adalet Meral; Okan, Mehmet

2015-10-01

The outcome of childhood acute lymphoblastic leukemia has improved because of intensive chemotherapy and supportive care. The frequency of adverse events has also increased, but the data related to acute central nervous system complications during acute lymphoblastic leukemia treatment are sparse. The purpose of this study is to evaluate these complications and to determine their long term outcome. We retrospectively analyzed the hospital reports of 323 children with de novo acute lymphoblastic leukemia from a 13-year period for acute neurological complications. The central nervous system complications of leukemic involvement, peripheral neuropathy, and post-treatment late-onset encephalopathy, and neurocognitive defects were excluded. Twenty-three of 323 children (7.1%) suffered from central nervous system complications during acute lymphoblastic leukemia treatment. The majority of these complications (n = 13/23; 56.5%) developed during the induction period. The complications included posterior reversible encephalopathy (n = 6), fungal abscess (n = 5), cerebrovascular lesions (n = 5), syndrome of inappropriate secretion of antidiuretic hormone (n = 4), and methotrexate encephalopathy (n = 3). Three of these 23 children (13%) died of central nervous system complications, one from an intracranial fungal abscess and the others from intracranial thrombosis. Seven of the survivors (n = 7/20; 35%) became epileptic and three of them had also developed mental and motor retardation. Acute central neurological complications are varied and require an urgent approach for proper diagnosis and treatment. Collaboration among the hematologist, radiologist, neurologist, microbiologist, and neurosurgeon is essential to prevent fatal outcome and serious morbidity. Copyright © 2015 Elsevier Inc. All rights reserved.

USE OF SUBCUTANEOUS METHOTREXATE FOR THE TREATMENT OF PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS: THE REMARCA TRIAL

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D. E. Karateev

2016-01-01

Full Text Available The early administration of methotrexate (MTX and the use of its high (by the rheumatology practice standards doses contribute to the enhanced efficiency of therapy and the reduced severity of rheumatoid arthritis (RA. One of the important merits of MTX in the treatment of RA is the possibility of adjusting its dose and choosing its (oral or subcutaneous administration routes, which makes it possible to individualize treatment. Particular emphasis has been recently placed just on a subcutaneous MTX formulation that creates prerequisites for substantially improving the efficiency of RA therapy. The paper gives the data of the REMARCA (Russian investigation of methotrexate and biologicals for early active arthritis trial assessing the results of RA treatment in the use of the subcutaneous MTX dosage form as a first-line drug and in the elaboration of management tactics for this disease.Subjects and methods. The investigation included 191 patients (34 men and 157 women with active RA; of whom 51.8% had very early RA (< 6 months' disease duration. 115 patients with RA completed a 24-month follow-up period; and their data were analyzed in more detail.Results and discussion. The findings may substantiate treatment policy based on the prescription of subcutaneous MTX (without previously administering its oral formulation in patients with early RA and high disease activity, starting the drug at 15 mg/week and rapidly escalating with the highest tolerable doses during 4-8 weeks, which allows remission (or low disease activity in the majority of patients without using glucocorticoids and biological agents.

Methotrexate-induced intestinal mucositis delays gastric emptying and gastrointestinal transit of liquids in awake rats

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Pedro M. G. Soares

2011-03-01

Full Text Available CONTEXT: Methotrexate and other anticancer agents can induce intestinal mucositis, which is one of the most common limiting factor that prevent further dose escalation of the methotrexate. OBJECTIVES: To evaluate the gastric emptying and gastrointestinal transit of liquids in methotrexate-induced intestinal mucositis. METHODS: Wistar rats received methotrexate (2.5 mg/kg/day for 3 days, subcutaneously or saline. After 1, 3 and 7 days, sections of duodenum, jejunum and ileum were removed for assessment of epithelial damage and myeloperoxidase activity (biochemical marker of granulocyte infiltration. Others rats were pre-treated with methotrexate or saline, gavage-fed after 3 or 7 days with a standard test liquid meal, and sacrificed 10, 20 or 30-min later. Gastric and small intestine dye recoveries were measured by spectrophotometry. RESULTS: After 3 days of methotrexate, there was an epithelial intestinal damage in all segments, with myeloperoxidase activity increase in both in duodenum and ileum. Seven days after methotrexate, we observed a complete reversion of this intestinal damage. There was an increase in gastric dye recoveries after 10, 20, and 30-min post-prandial intervals after 3 days, but not after 7 days, of methotrexate. Intestine dye recoveries were decreased in the first and second segments at 10 min, in the third at 20 min, and in the second and third at 30 min, only after 3 days of methotrexate treatment. CONCLUSION: Methotrexate-induced intestinal mucositis delays gastric emptying and gastrointestinal transit of liquids in awake rats.

Review of dextromethorphan administration in 18 patients with subacute methotrexate central nervous system toxicity.

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Afshar, Maryam; Birnbaum, Daniel; Golden, Carla

2014-06-01

The pathogenesis of methotrexate central nervous system toxicity is multifactorial, but it is likely related to central nervous system folate homeostasis. The use of folinate rescue has been described to decrease toxicity in patients who had received intrathecal methotrexate. It has also been described in previous studies that there is an elevated level of homocysteine in plasma and cerebrospinal fluid of patients who had received intrathecal methotrexate. Homocysteine is an N-methyl-D-aspartate receptor agonist. The use of dextromethorphan, noncompetitive N-methyl-D-aspartate receptor receptor antagonist, has been used in the treatment of sudden onset of neurological dysfunction associated with methotrexate toxicity. It remains unclear whether the dextromethorphan impacted the speed of recovery, and its use remains controversial. This study reviews the use of dextromethorphan in the setting of subacute methotrexate central nervous system toxicity. Charts of 18 patients who had sudden onset of neurological impairments after receiving methotrexate and were treated with dextromethorphan were reviewed. The use of dextromethorphan in most of our patients resulted in symptomatic improvement. In this patient population, earlier administration of dextromethorphan resulted in faster improvement of impairments and led to prevention of recurrence of seizure activity induced by methotrexate central nervous system toxicity. Our study provides support for the use of dextromethorphan in patients with subacute methotrexate central nervous system toxicity. Copyright © 2014 Elsevier Inc. All rights reserved.

Association between SLC19A1 Gene Polymorphism and High Dose Methotrexate Toxicity in Childhood Acute Lymphoblastic Leukaemia and Non Hodgkin Malignant Lymphoma: Introducing a Haplotype based Approach

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Kotnik, Barbara Faganel; Jazbec, Janez; Grabar, Petra Bohanec; Rodriguez-Antona, Cristina

2017-01-01

Abstract Background We investigated the clinical relevance of SLC 19A1 genetic variability for high dose methotrexate (HD-MTX) related toxicities in children and adolescents with acute lymphoblastic leukaemia (ALL) and non Hodgkin malignant lymphoma (NHML). Patients and methods Eighty-eight children and adolescents with ALL/NHML were investigated for the influence of SLC 19A1 single nucleotide polymorphisms (SNPs) and haplotypes on HD-MTX induced toxicities. Results Patients with rs2838958 TT genotype had higher probability for mucositis development as compared to carriers of at least one rs2838958 C allele (OR 0.226 (0.071–0.725), p < 0.009). Haplotype TGTTCCG (H4) statistically significantly reduced the risk for the occurrence of adverse events during treatment with HD-MTX (OR 0.143 (0.023–0.852), p = 0.030). Conclusions SLC 19A1 SNP and haplotype analysis could provide additional information in a personalized HD-MTX therapy for children with ALL/NHML in order to achieve better treatment outcome. However further studies are needed to validate the results. PMID:29333125

CAN INITIAL βHCG VALUES PREDICT THE NEED FOR SECOND DOSE OF METHOTREXATE IN MEDICAL MANAGEMENT OF ECTOPIC PREGNANCY?

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Priya Narayanan

2016-09-01

Full Text Available INTRODUCTION Prediction of requirement of second dose of methotrexate in patients treated with single dose would help in guiding treatment and counseling. The aim of this study is to determine whether pretreatment beta HCG values can predict the need for second dose of methotrexate in medically managed ectopic pregnancy. MATERIALS AND METHODS 46 women with ectopic pregnancies who were managed medically were included. The median of beta HCG titres on day 1, day 4 and day 7 was assessed in patients who responded to single dose methotrexate and those who required a second dose. RESULTS Out of the 46 patients studied, 41 responded to medical treatment (success 91%. 14 out of 41 required second dose of methotrexate (34%. Two patients required third dose of methotrexate. Five patients required surgery. DISCUSSION The median of day 1 and day 4 beta HCG values were not statistically different between those who responded to single dose methotrexate and those who required a second dose. Only day 7 values were found to be different. CONCLUSION The beta-hCG titre on day 1 and day 4 is not a predictor of requirement of second dose of methotrexate.

Methotrexate Associated Renal Impairment Is Related to Delayed Elimination of High-Dose Methotrexate

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Shi-Long Yang

2015-01-01

Full Text Available Although Methotrexate (MTX is an effective drug for the treatment of acute lymphoblastic leukemia (ALL, the toxicity remains a significant problem. In this prospective study, fifty-four patients with ALL were enrolled. 3 g or 5 g MTX/m2 was administered over 24 hours. Serum MTX concentrations were determined in 24, 48, and 96 hours after MTX infusion. Serum creatinine concentrations and creatinine clearance rate (CCR were determined before and 24 and 48 hours after MTX infusion. A total of 173 courses of MTX infusion were administered. The serum creatinine concentrations did not change much after MTX infusion while the CCR was gradually decreased. MTX clearance status was independently related to CCR decrease, with the risk of 8.07 to develop renal impairment in patients with delayed MTX elimination. Serum creatinine concentration, serum creatinine ratio, CCR, and CCR ratio at 24 hours were all related to MTX elimination delay. Patients with serum creatinine level >35.0 μmol/L, creatinine ratio >1.129, or CCR <100.0 mL/min were more likely to undergo MTX elimination delay. In conclusion, MTX could induce transient renal impairment and compromised renal function will delay MTX clearance. The serum creatinine concentration and the ratio and CCR are useful tools for evaluating MTX elimination status.

Synergistic activity of curcumin with methotrexate in ameliorating Freund's Complete Adjuvant induced arthritis with reduced hepatotoxicity in experimental animals.

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Banji, David; Pinnapureddy, Jyothi; Banji, Otilia J F; Saidulu, A; Hayath, Md Sikinder

2011-10-01

Methotrexate is employed in low doses for the treatment of rheumatoid arthritis. One of the major drawbacks with methotrexate is hepatotoxicity resulting in poor compliance of therapy. Curcumin is an extensively used spice possessing both anti-arthritic and hepatoprotective potential. The present study was aimed at investigating the effect of curcumin (30 and 100 mg/kg) in combination with subtherapeutic dose of methotrexate (1 mg/kg) is salvaging hepatotoxicity, oxidative stress and producing synergistic anti-arthritic action with methotrexate. Wistar albino rats were induced with arthritis by subplantar injection of Freund's Complete Adjuvant and pronounced arthritis was seen after 9 days of injection. Groups of animals were treated with subtherapeutic dose of methotrexate followed half an hour later with 30 and 100mg/kg of curcumin from day 9 up to days 45 by intraperitoneal route. Methotrexate treatment in Freund's Complete Adjuvant induced arthritic animals produced elevation in the levels of aminotransferases, alkaline phosphatase, total and direct bilirubin. Enhanced oxidative stress in terms of measured lipid peroxides was observed in the methotrexate treated group. Curcumin significantly circumvented hepatotoxicity induced by methotrexate as evidenced by a change in biochemical markers possibly due to its strong anti-oxidant action. Hepatoprotective potential of curcumin was also confirmed from histological evaluation. Sub-therapeutic dose of methotrexate elicited substantial anti-arthritic action when used in combination with curcumin implying that the latter potentiated its action. Concomitant administration of curcumin with methotrexate was also found to minimize liver damage. Copyright © 2011 Elsevier B.V. All rights reserved.

Intraocular methotrexate can induce extended remission in some patients in noninfectious uveitis.

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Taylor, Simon R J; Banker, Alay; Schlaen, Ariel; Couto, Cristobal; Matthe, Egbert; Joshi, Lavnish; Menezo, Victor; Nguyen, Ethan; Tomkins-Netzer, Oren; Bar, Asaf; Morarji, Jiten; McCluskey, Peter; Lightman, Sue

2013-01-01

To assess the outcomes of the intravitreal administration of methotrexate in uveitis. Multicenter, retrospective interventional case series of patients with noninfectious uveitis. Thirty-eight eyes of 30 patients were enrolled, including a total of 54 intravitreal injections of methotrexate at a dose of 400 µg in 0.1 mL. The primary outcome measure was visual acuity. Secondary outcome measures included control of intraocular inflammation and cystoid macular edema, time to relapse, development of adverse events, and levels of systemic corticosteroid and immunosuppressive therapy. Methotrexate proved effective in controlling intraocular inflammation and improving vision in 30 of 38 eyes (79%). The side effect profile was good, with no reported serious ocular adverse events and only one patient having an intraocular pressure of >21 mmHg. Of the 30 eyes that responded to treatment, 8 relapsed, but 22 (73%) entered an extended period of remission, with the Kaplan-Meier estimate of median time to relapse for the whole group being 17 months. The eight eyes that relapsed were reinjected and all responded to treatment. One eye relapsed at 3 months, but 7 eyes again entered extended remission. Of the 14 patients on systemic therapy at the start of the study, 8 (57%) were able to significantly reduce this following intravitreal methotrexate injection. In patients with uveitis and uveitic cystoid macular edema, intravitreal MTX can effectively improve visual acuity and reduce cystoid macular edema and, in some patients, allows the reduction of immunosuppressive therapy. Some patients relapse at 3 to 4 months, but a large proportion (73%) enter an extended period of remission of up to 18 months. This larger study extends the results obtained from previous smaller studies suggesting the viability of intravitreal methotrexate as a treatment option in uveitis.

Neurologic sequelae of methotrexate and ionizing radiation: a new classification

International Nuclear Information System (INIS)

Bleyer, W.A.

1981-01-01

Therapy for prevention of central nervous system (CNS) leukemia has had a dramatic effect on disease-free survival in children with acute lymphoblastic leukemia (ALL). Now, a majority of children may be in complete remission indefinitely, having completed therapy years ago. Unfortunately, some of these long-term survivors have residual neurologic dysfunction, varying in severity from the not uncommon occurrence of mild intellectual deficit to the fortunately rare instance of debilitating leukoencephalopathy. To help identify inciting factors and ultimately render CNS prophylaxis less neurotoxic, this article attempts to categorize the types of neurotoxicities reported in patients treated with methotrexate (MTX) and ionizing radiation. A variety of clinical syndromes are described and related temporally to these treatment modalities. Analyzed in this way, combinations including CNS irradiation appear to be the most neurotoxic. The safest methods are the single modalities, of which high-dose iv MTX may be the least neurotoxic

Efficacy of Methotrexate in patients with plaque type psoriasis

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Haider, Sabiqa; Wahid, Zarnaz; Najam-us-Saher; Riaz, Farzana

2014-01-01

Objective: To assess the efficacy of Methotrexate in patients with plaque type psoriasis. Methods: This descriptive study was conducted in the department of Dermatology, Civil Hospital Karachi from September 2009 to March 2010. Seventy three patients between 18 to 50 years of age suffering from plaque type psoriasis with PASI score of >10 were included in the study after taking the informed consent. Oral methotrexate in a dose of 7.5 mg/week was given for 8 weeks. The data collected included demographic profile (age and gender), duration of disease, site of involvement, size of plaque, severity of plaque measured by Psoriasis Area and Severity Index (PASI) score before starting the treatment and at the end of treatment. Efficacy was labeled with a PASI score of ≤5 at the end of 8 weeks. Results: Out of 73 patients there were 45 (61.6%) males and 28 (38.4%) females. The mean ±SD age was 40.0±12.6 years. The mean baseline PASI score showed clear and comparable improvement from a mean ± SD PASI score of 14.8±4.2 to 4.9±4.3.Twenty nine (40%) patients had an almost complete remission during the 8 weeks of treatment. Partial remission was achieved in 44 (60%) patients. The clearance time for psoriasis ranged from 5-7 weeks (mean 6±0.89 weeks). Conclusion: Treatment with methotrexate for chronic plaque psoriasis brings satisfactory disease control and improved quality of life. PMID:25225524

PEG capped methotrexate silver nanoparticles for efficient anticancer activity and biocompatibility.

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Muhammad, Zarmina; Raza, Abida; Ghafoor, Sana; Naeem, Ayesha; Naz, Syeda Sohaila; Riaz, Sundus; Ahmed, Wajiha; Rana, Nosheen Fatima

2016-08-25

Nanocarriers endow tremendous benefits to the drug delivery systems depending upon the specific properties of either component. These benefits include, increase in the drug blood retention time, reduced efflux, additional toxicity and targeted delivery. Methotrexate (MTX) is clinically used for cancer treatment. Higher dosage of MTX results in hepatic and renal toxicity. In this study methotrexate silver nanoparticles (Ag-MTX) coated with polyethylene glycol (PEG) are synthesized and characterized. Their anticancer activity and biocompatibility is also evaluated. Ag-MTX nanoparticles are synthesized by chemical reduction method. They are characterized by Ultraviolet-Visible Spectroscopy and Fourier Transform Infrared Spectroscopy. Average size of PEG coated Ag-MTX nanoparticles (PEG-Ag-MTX nanoparticles) is 12nm. These particles exhibited improved anticancer activity against MCF-7 cell line. Hemolytic activity of these particles was significantly less than MTX. PEG-Ag-MTX nanoparticles are potential nanocarrier of methotrexate which may offer MTX based cancer treatment with reduced side effects. In-vivo investigations should be carried out to explore them in detail. Copyright © 2016 Elsevier B.V. All rights reserved.

Mechanisms of immunological eradication of a syngeneic guinea pig tumor. II. Effect of methotrexate treatment and T cell depletion of the recipient on adoptive immunity

International Nuclear Information System (INIS)

Shu, S.; Fonseca, L.S.; Hunter, J.T.; Rapp, H.J.

1983-01-01

The influence of methotrexate on the development of immunity to the line 10 hepatoma was studied in guinea pigs. Chronic methotrexate treatment had no apparent effect on the ability of immune guinea pigs to suppress the growth of inoculated tumor cells. In contrast, the same methotrexate regimen inhibited the development of tumor immunity if started before the 8th day after immunization with a vaccine containing viable line 10 cells admixed with Bacillus Calmette-Guerin (BCG) cell walls. Thus, methotrexate selectively inhibited the afferent limb of the immune response. In adoptive transfer experiments, methotrexate-treated recipient guinea pigs were capable of being passively sensitized with immune spleen cells, indicating that the primary cell-mediated immune response of the recipient was not required for adoptive immunity. The contribution of recipient T cells in adoptive immunity was further investigated in guinea pigs deleted of T cells by thymectomy, irradiation, and bone marrow reconstitution. Despite demonstrable deficiency in T lymphocyte reactions, B animals were fully capable of rejecting tumors after transfer of immune cells. These results suggest that the expression of adoptive immunity was independent of recipient T cell participation. In addition, sublethal irradiation of immune spleen cells prior to adoptive transfer abolished their efficacy. Proliferation of transferred immune cells in the recipient may be essential for expression of adoptive immunity

Yellow fever vaccine used in a psoriatic arthritis patient treated with methotrexate

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Štuhec, Matej

2015-01-01

The yellow fever vaccines on the market are contraindicated for immunocompromised and elderly patients. A case of yellow fever vaccine used in a 27-year-old Slovenian male with psoriatic arthritis during treatment with methotrexate is described. We demonstrate a positive case, since there were noadverse effects in concurrent administration of yellow fever vaccine and methotrexate. This patient did not show severe adverse reactions and did not contract yellow fever despite potential exposure. ...

Case report: AREB in a patient with rheumatoid arthritis treated with methotrexate and infliximab

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Giuseppe Rossi

2011-09-01

Full Text Available Anti TNF-a drugs seem to be the new frontier of Rheumatoid Arthritis (RA therapy. The association infliximab methotrexate has been approved for the treatment of RA not responding to the classic therapy, but the short clinical experience in using antiTNF-a molecules brings to segnalation of new risks or adverse events. We describe a case of a patient, treated for many years with classic RA therapy, which developed a refractory anemia after treatment with association infliximab-methotrexate.

Methotrexate

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... lymphoma, and leukemia (cancer that begins in the white blood cells). Methotrexate is in a class of ... In case of overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. If the victim has ...

Non-infectious chemotherapy-associated acute toxicities during childhood acute lymphoblastic leukemia therapy

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Schmiegelow, Kjeld; Müller, Klaus Gottlob; Mogensen, Signe Sloth

2017-01-01

obstruction syndrome, endocrinopathies (especially steroid-induced adrenal insufficiency and hyperglycemia), high-dose methotrexate-induced nephrotoxicity, asparaginase-associated hypersensitivity, pancreatitis, and hyperlipidemia. Few of the non-infectious acute toxicities are associated with clinically...

Non-infectious chemotherapy-associated acute toxicities during childhood acute lymphoblastic leukemia therapy [version 1; referees: 3 approved

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Kjeld Schmiegelow

2017-04-01

Full Text Available During chemotherapy for childhood acute lymphoblastic leukemia, all organs can be affected by severe acute side effects, the most common being opportunistic infections, mucositis, central or peripheral neuropathy (or both, bone toxicities (including osteonecrosis, thromboembolism, sinusoidal obstruction syndrome, endocrinopathies (especially steroid-induced adrenal insufficiency and hyperglycemia, high-dose methotrexate-induced nephrotoxicity, asparaginase-associated hypersensitivity, pancreatitis, and hyperlipidemia. Few of the non-infectious acute toxicities are associated with clinically useful risk factors, and across study groups there has been wide diversity in toxicity definitions, capture strategies, and reporting, thus hampering meaningful comparisons of toxicity incidences for different leukemia protocols. Since treatment of acute lymphoblastic leukemia now yields 5-year overall survival rates above 90%, there is a need for strategies for assessing the burden of toxicities in the overall evaluation of anti-leukemic therapy programs.

Methotrexate for primary biliary cirrhosis

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Giljaca, Vanja; Poropat, Goran; Stimac, Davor

2010-01-01

Methotrexate has been used to treat patients with primary biliary cirrhosis as it possesses immunosuppressive properties. The previously prepared version of this review from 2005 showed that methotrexate seemed to significantly increase mortality in patients with primary biliary cirrhosis. Since...... that last review version, follow-up data of the included trials have been published....

Comparison of central nervous system prophylaxis with cranial radiation and intrathecal methotrexate versus intrathecal methotrexate alone in acute lymphoblastic leukemia

International Nuclear Information System (INIS)

Muriel, F.S.; Svarch, E.; Pavlovsky, S.

1983-01-01

In acute lymphoblastic leukemia, central nervous system prophylaxis with irradiation plus intrathecal methotrexate (i.t. MTX) reduces the incidence of CNS relapse to 7%-15%. However, increased evidence of CNS delayed toxicity was recognized mainly in children as CT scan abnormalities and neuropsychologic alterations. Two questions were analyzed: (1) Will further doses of i.t. methotraxate and dexamethasone (i.t. MTX-DMT) decrease the incidence of CNS relapse. (2) Is i.t. MTX-DMT given during induction and maintenance as effective as cranium irradiation plus i.t. MTX-DMT. Incidence of primary CNS relapse in i.t. MTX-DMT-treated patients with a WBC count 50,000, it was 16% in the treated group and 19% in the control group. These patients were compared with patients which had received 3 doses of i.t. MTX-DMT alone during induction, 3 doses weekly during the first month of remission, and quarterly thereafter. The incidence of leukemia at 60 mo in patients with a WBC count 50,000 at 48 mo was 28% and 42% in the irradiated and nonirradiated group respectively. Complete remission remained at 15% and 16% respectively of patients disease-free at 48 mo. We conclude that (A) after cranial irradiation plus i.t. MTX-DMT X 5, the use of additional doses of i.t. MTX-DMT is not of further benefit in preventing CNS relapse; (B) use of i.t. MTX-DMT alone compares with cranial irradiation plus i.t. MTX-DMT in incidence of CNS relapse; and (C) relapse-free survival and survival in patients with a WBC count < 50.000 were significantly longer in those without cranial irradiation

Methotrexate in Alopecia Areata: A Report of Three Cases

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Batalla, Ana; Fl?rez, ?ngeles; Abalde, Teresa; V?zquez-Veiga, Hugo

2016-01-01

There are few studies about systemic treatment in severe cases of alopecia areata (AA), especially in the pediatric population. Although there is more experience with systemic corticosteroids, recent reports have suggested methotrexate (MTX) as an alternative treatment, with a relatively good outcome. We describe three cases of AA in children treated with MTX, two of them with successful results.

Solid lipid nanoparticles by coacervation loaded with a methotrexate prodrug: preliminary study for glioma treatment.

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Battaglia, Luigi; Muntoni, Elisabetta; Chirio, Daniela; Peira, Elena; Annovazzi, Laura; Schiffer, Davide; Mellai, Marta; Riganti, Chiara; Salaroglio, Iris Chiara; Lanotte, Michele; Panciani, Pierpaolo; Capucchio, Maria Teresa; Valazza, Alberto; Biasibetti, Elena; Gallarate, Marina

2017-03-01

Methotrexate-loaded biocompatible nanoparticles were tested for preliminary efficacy in glioma treatment. Behenic acid nanoparticles, prepared by the coacervation method, were loaded with the ester prodrug didodecylmethotrexate, which was previously tested in vitro against glioblastoma human primary cultures. Nanoparticle conjugation with an ApoE mimicking chimera peptide was performed to obtain active targeting to the brain. Biodistribution studies in healthy rats assessed the superiority of ApoE-conjugated formulation, which was tested on an F98/Fischer glioma model. Differences were observed in tumor growth rate (measured by MRI) between control and treated rats. In vitro tests on F98 cultured cells assessed their susceptibility to treatment, with consequent apoptosis, and allowed us to explain the apoptosis observed in glioma models.

Crisis management in the treatment of childhood acute lymphoblastic leukemia: putting right what can go wrong (emergency complications of disease and treatment).

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Hough, Rachael; Vora, Ajay

2017-12-08

The improvement in overall survival in children with acute lymphoblastic leukemia (ALL) over the last 5 decades has been considerable, with around 90% now surviving long term. The risk of relapse has been reduced to such an extent that the risk of treatment-related mortality is now approaching that of mortality caused by relapse. Toxicities may also lead to the suboptimal delivery of chemotherapy (treatment delays, dose reductions, dose omissions), potentially increasing relapse risk, and short- and long-term morbidity, adding to the "burden of therapy" in an increasing number of survivors. Thus, the need to reduce toxicity in pediatric ALL is becoming increasingly important. This work focuses on the risk factors, pathogenesis, clinical features, and emergency management of the life-threatening complications of ALL at presentation and during subsequent chemotherapy, including leucostasis, tumor lysis syndrome, infection, methotrexate encephalopathy, thrombosis, and pancreatitis. Potential strategies to abrogate these toxicities in the future are also discussed. © 2016 by The American Society of Hematology. All rights reserved.

Improving treatment with methotrexate in rheumatoid arthritis-development of a multimedia patient education program and the MiRAK, a new instrument to evaluate methotrexate-related knowledge.

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Ciciriello, Sabina; Buchbinder, Rachelle; Osborne, Richard H; Wicks, Ian P

2014-02-01

To develop and test an evidence-based, multimedia patient education program (MPEP) about methotrexate (MTX) treatment for rheumatoid arthritis (RA) and a new measure of patient knowledge [Methotrexate in Rheumatoid Arthritis Knowledge test (MiRAK)]. The content of the MPEP and MiRAK was guided by concept-mapping workshops with patients (N = 24), literature review, health professional, and expert linguistic input. The MPEP and MiRAK underwent multiple stages of testing and revision with patients and health professionals. The MiRAK was administered to RA patients (N = 169) and its properties examined using the Rasch analyses. A subset of respondents (N = 131) repeated the MiRAK to determine test-retest reliability. A before-after pilot study with patients who had recently started MTX (N = 31) tested responsiveness of the MiRAK and feasibility and acceptability of the MPEP. A DVD of 24-minutes duration was produced that presents detailed, evidence-based information about MTX. The Rasch analyses of the 60 MiRAK items revealed that these could be summated into a single score. The MiRAK had good model fit, supporting internal construct validity, good internal consistency (person separation index; 0.84), test-retest reliability (ICC; 0.89), and ability to detect change (ES; 2.38). The before-after study suggested that patients could self-administer the MPEP, with the majority finding it informative and easy to use. We developed a MPEP about MTX treatment for RA, which was found to be user-friendly and easily implementable. The MiRAK is a new scale, testing a broad spectrum of MTX knowledge. Analyses revealed strong evidence for its validity and reliability. Copyright © 2014 Elsevier Inc. All rights reserved.

A decrease in vitamin D levels is associated with methotrexate-induced oral mucositis in children with acute lymphoblastic leukemia.

Science.gov (United States)

Oosterom, N; Dirks, N F; Heil, S G; de Jonge, R; Tissing, W J E; Pieters, R; van den Heuvel-Eibrink, M M; Heijboer, A C; Pluijm, S M F

2018-06-19

Children with acute lymphoblastic leukemia (ALL) are at increased risk of vitamin D deficiency, which might make them more susceptible to developing adverse events. Previous studies showed that low vitamin D levels were associated with an increased inflammatory mucosal state and impaired mucosal tissue barriers. We examined the prevalence of vitamin D deficiency and studied the association between vitamin D levels and methotrexate (MTX)-induced oral mucositis in pediatric ALL. We assessed 25-hydroxyvitamin D (25(OH)D 3 ) and 24,25-dihydroxyvitamin D (24,25(OH) 2 D 3 ) levels in 99 children with ALL before the start of 4 × 5 g/m 2 high-dose methotrexate (HD-MTX) (T0) and in 81/99 children after discontinuation of HD-MTX (T1). Two cutoff values for vitamin D deficiency exist: 25(OH)D 3 levels D deficiency occurred in respectively 8% ( 4 years of age as compared to children between 1 and 4 years of age. A decrease in 25(OH)D 3 levels during HD-MTX therapy was associated with developing severe oral mucositis (OR 1.6; 95% CI [1.1-2.4]). 25(OH)D 3 and 24,25(OH) 2 D 3 levels at T0 and the change in 24,25(OH) 2 D 3 levels during therapy were not associated with the development of severe oral mucositis. This study showed that vitamin D deficiency occurs frequently in pediatric ALL patients above the age of 4 years. A decrease in 25(OH)D 3 levels during MTX therapy was observed in children with ALL that developed severe oral mucositis.

Effects of methotrexate on rat parotid and submandibular glands and their secretions

International Nuclear Information System (INIS)

McBride, R.K.

1986-01-01

Experimental animals were injected intraperitoneally with methotrexate for 3 days. Parotid and submandibular main ducts were cannulated and saliva flow was evoked by either intravenous infusion of acetylcholine or an intravenous injection of benthanechol. Methotrexate was found to reduce significantly mean food consumption, body weight, and parotid gland wet weights. Experimental animal salivary total gland DNA levels were not different, but total parotid gland RNA, protein, amylase and water content, and submandibular gland RNA were significantly lower compared to control. Acetylcholine, but not bethanechol, evoked parotid protein and amylase outputs and submandibular protein output from experimental animals were significantly higher than the control groups'. The increased outputs were apparently linked to β-adrenergic receptor activation, since hexamethonium or propranolol eliminated the significant increases while phenoxybenzamine did not. Plasma catecholamine levels were significantly higher in the methotrexate treated animals and probably played a role in the salivary gland β-adrenergic activation. Methotrexate treatment significantly increased the submandibular gland β-adrenergic receptor concentration as determined by [ 3 H]-dihydroalprenolol receptor binding assays. Muscarinic receptor concentrations determined with [ 3 H]-quinuclidninyl benzilate were not changed

Yellow fever vaccine used in a psoriatic arthritis patient treated with methotrexate: a case report.

Science.gov (United States)

Stuhec, Matej

2014-01-01

The yellow fever vaccines on the market are contraindicated for immunocompromised and elderly patients. A case of yellow fever vaccine used in a 27-year-old Slovenian male with psoriatic arthritis during treatment with methotrexate is described. We demonstrate a positive case, since there were no adverse effects in concurrent administration of yellow fever vaccine and methotrexate. This patient did not show severe adverse reactions and did not contract yellow fever despite potential exposure. More research is needed on possible adverse effects of concurrent administration of yellow fever vaccine and methotrexate to determine the potential of this method for more frequent use.

Vorinostat plus tacrolimus/methotrexate to prevent GVHD after myeloablative conditioning, unrelated donor HCT.

Science.gov (United States)

Choi, Sung Won; Braun, Thomas; Henig, Israel; Gatza, Erin; Magenau, John; Parkin, Brian; Pawarode, Attaphol; Riwes, Mary; Yanik, Greg; Dinarello, Charles A; Reddy, Pavan

2017-10-12

The oral histone deacetylase (HDAC) inhibitor (vorinostat) is safe and results in low incidence of acute graft-versus-host disease (GVHD) after reduced-intensity conditioning, related donor hematopoietic cell transplantation (HCT). However, its safety and efficacy in preventing acute GVHD in settings of heightened clinical risk that use myeloablative conditioning, unrelated donor (URD), and methotrexate are not known. We conducted a prospective, phase 2 study in this higher-risk setting. We enrolled 37 patients to provide 80% power to detect a significant difference in grade 2 to 4 acute GVHD of 50% compared with a reduction in target to 28%. Eligibility included adults with a hematological malignancy to receive myeloablative HCT from an available 8/8-HLA matched URD. Patients received GVHD prophylaxis with tacrolimus and methotrexate. Vorinostat (100 mg twice daily) was started on day -10 and continued through day +100 post-HCT. Median age was 56 years (range, 18-69 years), and 95% had acute myelogenous leukemia or high-risk myelodysplastic syndrome. Vorinostat was safe and tolerable. The cumulative incidence of grade 2 to 4 acute GVHD at day 100 was 22%, and for grade 3 to 4 it was 8%. The cumulative incidence of chronic GVHD was 29%; relapse, nonrelapse mortality, GVHD-free relapse-free survival, and overall survival at 1 year were 19%, 16%, 47%, and 76%, respectively. Correlative analyses showed enhanced histone (H3) acetylation in peripheral blood mononuclear cells and reduced interleukin 6 ( P = .028) and GVHD biomarkers (Reg3, P = .041; ST2, P = .002) at day 30 post-HCT in vorinostat-treated subjects compared with similarly treated patients who did not receive vorinostat. Vorinostat for GVHD prevention is an effective strategy that should be confirmed in a randomized phase 3 study. This trial was registered at www.clinicaltrials.gov as #NCT01790568. © 2017 by The American Society of Hematology.

Hypoxia-induced resistance to doxorubicin and methotrexate in human melanoma cell lines in vitro.

Science.gov (United States)

Sanna, K; Rofstad, E K

1994-07-15

Rodent cell lines can develop resistance to doxorubicin and methotrexate during hypoxic stress. This has so far not been observed in human tumor cell lines. The purpose of our communication is to show that doxorubicin and methotrexate resistance can also develop in human melanoma cells during exposure to hypoxia. Four cell lines (BEX-c, COX-c, SAX-c, WIX-c) have been studied. Cells were exposed to hypoxia (O2 concentration WIX-c. BEX-c and SAX-c were sensitive to methotrexate without hypoxia pre-treatment, whereas COX-c and WIX-c were resistant initially. Hypoxia-induced drug resistance was present immediately after reoxygenation and tended to decrease with time but remained statistically significant even 42 hr after reoxygenation.

Treatment efficacy and methotrexate-related toxicity in patients with rheumatoid arthritis receiving methotrexate in combination with adalimumab.

Science.gov (United States)

Burmester, Gerd R; Kaeley, Gurjit S; Kavanaugh, Arthur F; Gabay, Cem; MacCarter, Daryl K; Nash, Peter; Takeuchi, Tsutomu; Goss, Sandra L; Rodila, Ramona; Chen, Kun; Kupper, Hartmut; Kalabic, Jasmina

2017-01-01

Treatment of rheumatoid arthritis (RA) with a combination of methotrexate (MTX)+adalimumab (ADA) is more effective than ADA monotherapy. We assessed the toxicity of different doses of MTX and treatment efficacy of ADA+MTX in two trials. Data originated from CONCERTO, in patients with early RA initiating ADA+ 2.5, 5, 10 or 20 mg/week MTX for 26 weeks; and MUSICA, in patients with an inadequate response to MTX initiating ADA+ 7.5 or 20 mg/week MTX for 24 weeks. Efficacy was assessed by the American College of Rheumatology 50 (ACR50). Patient-reported MTX-related toxicity information was collected at each visit on 18 prespecified MTX-related adverse events (AE) in the MTX label. In CONCERTO, ACR50 rates increased over time, ranging from 54% to 68% at week 26, while AE rates remained steady, ranging from 2.4% to 17.8% at week 26. Of 395 patients, 113 (28.6%) reported 345 MTX-related AEs, including one serious AE (SAE, excessive fatigue and/or malaise); 10 AEs (in two patients) led to study discontinuation. In MUSICA, ACR50 rates increased over time, and were 32.3% and 37.5% at week 24, while MTX-related AE rates remained steady and were 6.5% at week 24. Of 309 patients, 71 (23%) reported 185 MTX-related AEs, including 5 SAEs (four infections and one fever/chills); six AEs (in four patients) led to study discontinuation. In patients with RA initiating ADA+MTX combination, treatment efficacy was achieved and increased throughout both trials, while rates of MTX-related AEs remained steady. MTX-related AEs were observed in up to 30% of patients and most were mild. MTX was discontinued by 0.5%-1.3% of patients. MUSICA (NCT01185288), CONCERTO (NCT01185301), Post results.

The acitretin and methotrexate combination therapy for psoriasis vulgaris achieves higher effectiveness and less liver fibrosis.

Science.gov (United States)

An, Jingang; Zhang, Dingwei; Wu, Jiawen; Li, Jiong; Teng, Xiu; Gao, Xiaomin; Li, Ruilian; Wang, Xiuying; Xia, Linlin; Xia, Yumin

2017-07-01

Both acitretin and methotrexate are effective in ameliorating psoriatic lesion. However, their combination has been seldom reported in the treatment of psoriasis because of the warning regarding the potential hepatotoxicity of the drug interactions. This study was designed to investigate the effectiveness of such combination therapy for psoriasis vulgaris, and the potential benefit as well as side effect during the treatment. Thirty-nine patients with psoriasis vulgaris were treated with acitretin, methotrexate or their combination or as control. Similarly, K14-VEGF transgenic psoriasis-like mice were treated with these drugs. Human primary keratinocytes and hepatic stellate cells were used for analyzing their effect in vitro. The results showed that the combination therapy exhibited higher effectiveness in remitting skin lesion, but did not significantly affect the liver function of both patients and mice. Moreover, the combination groups showed less elevation of profibrotic factors in sera when compared with methotrexate alone groups accordingly. Furthermore, primary keratinocytes expressed more involucrin as well as loricrin and proliferated more slowly on the combined stimulation. Interestingly, such combination treatment induced lower expression of profibrotic factors in hepatic stellate cells. In conclusion, the acitretin-methotrexate combination therapy for psoriasis vulgaris can achieve higher effectiveness and result in less liver fibrosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effectiveness of disease-modifying antirheumatic drug co-therapy with methotrexate and leflunomide in rituximab-treated rheumatoid arthritis patients

DEFF Research Database (Denmark)

Chatzidionysiou, Katerina; Lie, Elisabeth; Nasonov, Evgeny

2012-01-01

is an effective and safe alternative to methotrexate as concomitant treatment with rituximab. Slightly better results were obtained by the combination of rituximab and leflunomide than rituximab and methotrexate, raising the possibility of a synergistic effect of leflunomide and rituximab.......OBJECTIVES: To compare the effectiveness and safety of rituximab alone or in combination with either methotrexate or leflunomide.METHODS: 10 European registries submitted anonymised datasets with baseline, 3, 6, 9 and 12-month clinical data from patients who started rituximab.RESULTS: 1195 patients...

CT studies before and after CNS treatment for acute lymphoblastic leukemia and malignant non-Hodgkin's lymphoma in childhood

International Nuclear Information System (INIS)

Kretzschmar, K.; Gutjahr, P.; Kutzner, J.

1980-01-01

CT was performed on 72 children with acute lymphoblasitc leukemia or non-Hodgkin's lymphoma. Thirty-two of these patients were investigated prior to CNS radiation and intrathecal methotrexate therapy. Ten of these patients (31%) were known to have hydrocephalic dilatation of the CSF spaces. Clinical data and subsequent observations with analysis of the CT findings show that no difference in the attenuation values of brain tissue occurs in the absence of a CNS relapse. The percentage of abnormal findings before and after therapy remains constant. The adverse late effects described in the CT literature seem principally to be damage diagnosed too late. It is questionable if the CT demonstration of dilated CSF spaces before treatment has a prognostic significance. (orig.)

Anti-TNFα agents and methotrexate in spondyloarthritis related uveitis in a Chinese population.

Science.gov (United States)

Lian, Fan; Zhou, Jun; Wei, Cui; Wang, Yu; Xu, Hanshi; Liang, Liuqin; Yang, Xiuyan

2015-11-01

This study seeks to evaluate the clinical characteristics of spondyloarthritis (SpA)-related uveitis in a cohort from South China and to assess the efficacy and safety of therapies based on TNF blockers. SpA patients with uveitis admitted to a south China hospital were enrolled. Demographic information, clinical characteristics, laboratory findings, intraocular inflammation, visual acuity, macular thickness, and treatments were documented. Of the 1,036 SpA patients reviewed, 182 had uveitis. Ankylosing spondylitis (AS) was the most common subtype. Unilateral uveitis was found in 51 cases (51/182, 28.0%), and unilateral alternating uveitis was found in 75 cases (75/182, 41.2%). Half of the cases were recurrent uveitis (52.2%), and acute onset was common (76.4%). The most serious complication was vision loss (0.5%). No significant difference in disease activity was found between the SpA patients with or without uveitis. Predominant improvements were found in cases treated with all three anti-TNFs (infliximab, adalimumab, and etanercept) and anti-TNFs plus methotrexate (MTX). Monotherapy of methotrexate was not adequate for inducing remission. Monotherapy of etanercept was not as effective as adalimumab and infliximab, mainly in the prevention of recurrence. No significant difference in effectiveness was found among the three anti-TNFs if MTX was added. Etanercept plus MTX were well tolerated. Infliximab and adalimumab were associated with more tuberculosis and/or hepatitis flares. Uveitis is common in SpA patients. Severe complications may develop in prolonged and intractable cases. Treatments based on anti-TNFs had good clinical response, and better safety documentation were observed in etanercept plus MTX compared to the other two anti-TNF monoclonal antibodies plus MTX.

Effects of methotrexate on rat parotid and submandibular glands and their secretions

Energy Technology Data Exchange (ETDEWEB)

McBride, R.K.

1986-01-01

Experimental animals were injected intraperitoneally with methotrexate for 3 days. Parotid and submandibular main ducts were cannulated and saliva flow was evoked by either intravenous infusion of acetylcholine or an intravenous injection of benthanechol. Methotrexate was found to reduce significantly mean food consumption, body weight, and parotid gland wet weights. Experimental animal salivary total gland DNA levels were not different, but total parotid gland RNA, protein, amylase and water content, and submandibular gland RNA were significantly lower compared to control. Acetylcholine, but not bethanechol, evoked parotid protein and amylase outputs and submandibular protein output from experimental animals were significantly higher than the control groups'. The increased outputs were apparently linked to ..beta..-adrenergic receptor activation, since hexamethonium or propranolol eliminated the significant increases while phenoxybenzamine did not. Plasma catecholamine levels were significantly higher in the methotrexate treated animals and probably played a role in the salivary gland ..beta..-adrenergic activation. Methotrexate treatment significantly increased the submandibular gland ..beta..-adrenergic receptor concentration as determined by (/sup 3/H)-dihydroalprenolol receptor binding assays. Muscarinic receptor concentrations determined with (/sup 3/H)-quinuclidninyl benzilate were not changed.

Early medical abortion with methotrexate and misoprostol.

Science.gov (United States)

Borgatta, L; Burnhill, M S; Tyson, J; Leonhardt, K K; Hausknecht, R U; Haskell, S

2001-01-01

To evaluate the introduction of an early medical abortion program with methotrexate and misoprostol, using a standardized protocol. A total of 1973 women at 34 Planned Parenthood sites participated in a case series of early medical abortion. Ultrasound was used to confirm gestational age of less than 49 days from the first day of the last menstrual period. Women were given intramuscular methotrexate 50 mg/m(2) of body surface area on day 1, and then they inserted misoprostol 800 microg vaginally at home on day 5, 6, or 7. Women were advised to have a suction curettage if the pregnancy appeared viable 2 weeks after methotrexate or if any gestational sac persisted 4 weeks after methotrexate. Outcomes were complete medical abortion and suction curettage. Sixteen hundred fifty-nine women (84.1%) had a complete medical abortion, and 257 (13.0%) had suction curettage. The most common reason for curettage was patient option (8.9%). At 2 weeks after methotrexate use, 1.4% of women had curettage because of a viable pregnancy; at 4 weeks, 1.6% of women had curettage because of a persistent but nonviable pregnancy. One percent of women had curettage because of physician recommendation, most commonly for bleeding. Suction curettage rates decreased with site experience (P <.006) and were lower at early gestational ages (P <.004) and in nulliparous women (P <.004). Medical abortion with methotrexate and misoprostol is safe and effective and can be offered in a community setting.

Oral methotrexate/6-mercaptopurine may be superior to a multidrug LSA2L2 Maintenance therapy for higher risk childhood acute lymphoblastic leukemia: results from the NOPHO ALL-92 study

DEFF Research Database (Denmark)

Schmiegelow, Kjeld; Heyman, Mats; Kristinsson, Jon

2009-01-01

The importance of maintenance therapy for higher risk childhood acute lymphoblastic leukemia (ALL) is uncertain. Between 1992 and 2001 the Nordic Society for Pediatric Haematology/Oncology compared in a nonrandomized study conventional oral methotrexate (MTX)/6-mercaptopurine (6MP) maintenance...... therapy (P=0.04) were both related to an increased risk of an event (overall P value of the Cox model: 0.003), whereas neither sex, age at diagnosis, administration of central nervous system irradiation, nor presence of a day 15 bone marrow with > or =25% versus

Serum Creatinine Versus Plasma Methotrexate Levels to Predict Toxicities in Children Receiving High-dose Methotrexate.

Science.gov (United States)

Tiwari, Priya; Thomas, M K; Pathania, Subha; Dhawan, Deepa; Gupta, Y K; Vishnubhatla, Sreenivas; Bakhshi, Sameer

2015-01-01

Facilities for measuring methotrexate (MTX) levels are not available everywhere, potentially limiting administration of high-dose methotrexate (HDMTX). We hypothesized that serum creatinine alteration after HDMTX administration predicts MTX clearance. Overall, 122 cycles in 50 patients of non-Hodgkin lymphoma or acute lymphoblastic leukemia aged ≤18 years receiving HDMTX were enrolled prospectively. Plasma MTX levels were measured at 12, 24, 36, 48, 60, and 72 hours; serum creatinine was measured at baseline, 24, 48, and 72 hours. Correlation of plasma MTX levels with creatinine levels and changes in creatinine from baseline (Δ creatinine) were evaluated. Plasma MTX levels at 72 hours showed positive correlation with serum creatinine at 48 hours (P = .011) and 72 hours (P = .013) as also Δ creatinine at 48 hours (P = .042) and 72 hours (P = .045). However, cut-off value of either creatinine or Δ creatinine could not be established to reliably predict delayed MTX clearance. Greater than 50% Δ creatinine at 48 and 72 hours significantly predicted grade 3/4 leucopenia (P = .036 and P = .001, respectively) and thrombocytopenia (P = .012 and P = .009, respectively) but not mucositis (P = .827 and P = .910, respectively). Delayed MTX elimination did not predict any grade 3/4 toxicity. In spite of demonstration of significant correlation between serum creatinine and Δ creatinine with plasma MTX levels at 72 hours, cut-off value of either variable to predict MTX delay could not be established. Thus, either of these cannot be used as a surrogate for plasma MTX estimation. Interestingly, Δ creatinine effectively predicted hematological toxicities, which were not predicted by delayed MTX clearance.

Diltiazem-induced acute generalised exanthematous pustulosis.

Science.gov (United States)

Wakelin, S H; James, M P

1995-07-01

Pustulation is a major feature in several different dermatoses, and it may also occur as a manifestation of drug hypersensitivity. Acute generalized exanthematous pustulosis (AGEP) is an uncommon eruption characterized by acute, extensive formation of sterile pustules, fever and peripheral blood leucocytosis. It shares several clinical and histological features in common with pustular psoriasis. Most reported cases have been triggered by ingestion of broad spectrum antibiotics, particularly betalactams and macrolides. There is usually rapid resolution of the eruption on drug withdrawal. We report the case of a 58 year-old woman who developed AGEP shortly after commencing treatment with the calcium channel blocker diltiazem hydrochloride. The eruption followed a biphasic course, and improved following treatment with systemic corticosteroids and methotrexate. AGEP appears to be a rare adverse cutaneous reaction to diltiazem, whereas a wide range of other skin eruptions have been reported more commonly with this drug.

Brain Activity Associated With Attention Deficits Following Chemotherapy for Childhood Acute Lymphoblastic Leukemia.

Science.gov (United States)

Fellah, Slim; Cheung, Yin T; Scoggins, Matthew A; Zou, Ping; Sabin, Noah D; Pui, Ching-Hon; Robison, Leslie L; Hudson, Melissa M; Ogg, Robert J; Krull, Kevin R

2018-05-21

The impact of contemporary chemotherapy treatment for childhood acute lymphoblastic leukemia on central nervous system activity is not fully appreciated. Neurocognitive testing and functional magnetic resonance imaging (fMRI) were obtained in 165 survivors five or more years postdiagnosis (average age = 14.4 years, 7.7 years from diagnosis, 51.5% males). Chemotherapy exposure was measured as serum concentration of methotrexate following high-dose intravenous injection. Neurocognitive testing included measures of attention and executive function. fMRI was obtained during completion of two tasks, the continuous performance task (CPT) and the attention network task (ANT). Image analysis was performed using Statistical Parametric Mapping software, with contrasts targeting sustained attention, alerting, orienting, and conflict. All statistical tests were two-sided. Compared with population norms, survivors demonstrated impairment on number-letter switching (P < .001, a measure of cognitive flexibility), which was associated with treatment intensity (P = .048). Task performance during fMRI was associated with neurocognitive dysfunction across multiple tasks. Regional brain activation was lower in survivors diagnosed at younger ages for the CPT (bilateral parietal and temporal lobes) and the ANT (left parietal and right hippocampus). With higher serum methotrexate exposure, CPT activation decreased in the right temporal and bilateral frontal and parietal lobes, but ANT alerting activation increased in the ventral frontal, insula, caudate, and anterior cingulate. Brain activation during attention and executive function tasks was associated with serum methotrexate exposure and age at diagnosis. These findings provide evidence for compromised and compensatory changes in regional brain function that may help clarify the neural substrates of cognitive deficits in acute lymphoblastic leukemia survivors.

Pharmacology and optimization of thiopurines and methotrexate in inflammatory bowel disease

DEFF Research Database (Denmark)

Coskun, Mehmet; Steenholdt, Casper; de Boer, Nanne K.

2016-01-01

Improving the efficacy and reducing the toxicity of thiopurines and methotrexate (MTX) have been areas of intense basic and clinical research. An increased knowledge on pharmacodynamics and pharmacokinetics of these immunomodulators has optimized treatment strategies in inflammatory bowel disease...

Whole brain magnetization transfer histogram analysis of pediatric acute lymphoblastic leukemia patients receiving intrathecal methotrexate therapy

Energy Technology Data Exchange (ETDEWEB)

Yamamoto, Akira [Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto-shi Kyoto 606-8507 (Japan)]. E-mail: yakira@kuhp.kyoto-u.ac.jp; Miki, Yukio [Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto-shi Kyoto 606-8507 (Japan)]. E-mail: mikiy@kuhp.kyoto-u.ac.jp; Adachi, Souichi [Department of Pediatrics, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto-shi Kyoto 606-8507 (Japan)]. E-mail: sadachi@kuhp.kyoto-u.ac.jp (and others)

2006-03-15

Background and purpose: The purpose of this prospective study was to evaluate the hypothesis that magnetization transfer ratio (MTR) histogram analysis of the whole brain could detect early and subtle brain changes nonapparent on conventional magnetic resonance imaging (MRI) in children with acute lymphoblastic leukemia (ALL) receiving methotrexate (MTX) therapy. Materials and methods: Subjects in this prospective study comprised 10 children with ALL (mean age, 6 years; range, 0-16 years). In addition to conventional MRI, magnetization transfer images were obtained before and after intrathecal and intravenous MTX therapy. MTR values were calculated and plotted as a histogram, and peak height and location were calculated. Differences in peak height and location between pre- and post-MTX therapy scans were statistically analyzed. Conventional MRI was evaluated for abnormal signal area in white matter. Results: MTR peak height was significantly lower on post-MTX therapy scans than on pre-MTX therapy scans (p = 0.002). No significant differences in peak location were identified between pre- and post-chemotherapy imaging. No abnormal signals were noted in white matter on either pre- or post-MTX therapy conventional MRI. Conclusions: This study demonstrates that MTR histogram analysis allows better detection of early and subtle brain changes in ALL patients who receive MTX therapy than conventional MRI.

Treatment of cervical pregnancy with ultrasound-guided local methotrexate injection.

Science.gov (United States)

Yamaguchi, M; Honda, R; Erdenebaatar, C; Monsur, M; Honda, T; Sakaguchi, I; Okamura, Y; Ohba, T; Katabuchi, H

2017-12-01

Cervical pregnancy (CP) is a rare type of ectopic pregnancy. While methotrexate (MTX) is generally the first-line method of choice for clinically stable women, there is still no consensus on the most appropriate treatment for this abnormal pregnancy. The aim of this study was to investigate the efficacy of a single local MTX injection under transvaginal ultrasound guidance for the initial treatment of CP and to assess post-treatment fertility. We reviewed retrospectively 15 patients with CP treated with local MTX injection under transvaginal ultrasound guidance. In all patients, the serum human chorionic gonadotropin (hCG) levels were monitored and the gestational sac was evaluated using ultrasonography after treatment. Magnetic resonance imaging (MRI) was performed as necessary. We evaluated the patients' clinical characteristics and clinical course after treatment, the efficacy of the treatment and the post-treatment fertility in patients desiring subsequent pregnancy. The median estimated gestational age at the time of MTX injection was 6 + 2 (range, 5 + 2 to 11 + 0) weeks. All 15 patients were treated successfully, without the need for blood transfusion or surgical procedures; however, three patients required an additional local MTX injection due to a poor decline in serum hCG level following the initial injection, while one patient required uterine artery embolization due to persistent vaginal bleeding and an enlarging gestational sac with blood vessels visible on contrast-enhanced MRI. The mean time following initial MTX injection for hCG normalization was 43.8 (95% CI, 33.3-54.3) days and for resumption of menses was 68.4 (95% CI, 51.9-84.9) days. Seven of the 10 women desiring subsequent pregnancy following treatment had uneventful pregnancy, one became pregnant but miscarried spontaneously at 8 weeks of gestation, one was treated by laparoscopic surgery after diagnosis of a tubal pregnancy and one did not conceive. A single, ultrasound

Virgin coconut oil supplementation attenuates acute chemotherapy hepatotoxicity induced by anticancer drug methotrexate via inhibition of oxidative stress in rats.

Science.gov (United States)

Famurewa, Ademola C; Ufebe, Odomero G; Egedigwe, Chima A; Nwankwo, Onyebuchi E; Obaje, Godwin S

2017-03-01

The emerging health benefit of virgin coconut oil (VCO) has been associated with its potent natural antioxidants; however, the antioxidant and hepatoprotective effect of VCO against methotrexate-induced liver damage and oxidative stress remains unexplored. The study explored the antioxidant and hepatoprotective effects of VCO against oxidative stress and liver damage induced by anticancer drug methotrexate (MTX) in rats. Liver damage was induced in Wistar rats pretreated with dietary supplementation of VCO (5% and 15%) by intraperitoneal administration of MTX (20mg/kg bw) on day 10 only. After 12days of treatment, assays for serum liver biomarkers (aminotransferases), alkaline phosphatase, albumin and total protein as well as hepatic content of malondialdehyde, reduced glutathione and antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase) were carried out. Liver was used to examine histopathological changes. MTX administration induced significant increase in serum liver enzymes along with marked decrease in albumin and total protein compared to control group. Hepatic activities of antioxidant enzymes were significantly decreased, while malondialdehyde increased significantly. Treatment with VCO supplemented diet prior to MTX administration attenuated MTX-induced liver injury and oxidative stress evidenced by significant improvements in serum liver markers, hepatic antioxidant enzymes and malondialdehyde comparable to control group. Histopathological alterations were prevented and correlated well with the biochemical indices. The study suggests antioxidant and hepatoprotective effects of VCO supplementation against hepatotoxicity and oxidative damage via improving antioxidant defense system in rats. Our findings may have beneficial application in the management of hepatotoxicity associated with MTX cancer chemotherapy. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Yellow fever vaccine used in a psoriatic arthritis patient treated with methotrexate: a case report:

OpenAIRE

Štuhec, Matej

2014-01-01

The yellow fever vaccines on the market are contraindicated for immunocompromised and elderly patients. A case of yellow fever vaccine used in a 27-year-old Slovenian male with psoriatic arthritis during treatment with methotrexate is described. We demonstrate a positive case, since there were noadverse effects in concurrent administration of yellow fever vaccine and methotrexate. This patient did not show severe adverse reactions and did not contract yellow fever despite potential exposure. ...

Myelotoxicity after high-dose methotrexate in childhood acute leukemia is influenced by 6-mercaptopurine dosing but not by intermediate thiopurine methyltransferase activity

DEFF Research Database (Denmark)

Levinsen, Mette; Rosthøj, Susanne; Nygaard, Ulrikka

2015-01-01

Purpose: Through enhancement of 6-mercaptopurine (6MP) bioavailability and inhibition of purine de novo synthesis, high-dose methotrexate (HD-MTX) may increase incorporation into DNA of 6-thioguanine nucleotides, the cytotoxic metabolites of 6MP. Patients with intermediate activity of thiopurine...... methyltransferase (TPMTIA) have higher cytosol 6-thioguanine nucleotide levels. We investigated toxicity following HD-MTX during MTX/6MP maintenance therapy in relation to 6MP and TPMT. Methods: Using linear mixed models, we explored myelo- and hepatotoxicity in relation to 6MP dosage and TPMT phenotype following 1......,749 HD-MTX courses to 411 children with acute lymphoblastic leukemia on maintenance therapy. Results: The degree of myelosuppression following HD-MTX was similar for patients with TPMTIA and patients with high TPMT activity (TPMTHA), when HD-MTX started with same blood counts and 6MP doses. However...

Microfluidic platform for dynamic in vitro optimization of methotrexate-loaded lipid nanoparticle delivery for personalized osteosarcoma treatment

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Muñoz-Hernando, M.; Macias, P.; Abella, M.; Desco, M.; Sharpe, S.; Vaquero, J.J.; Muñoz-Barrutia, M.

2016-07-01

Cancer is a leading cause of mortality in the world, with osteosarcoma being one of the most common types among children between 1 and 14 years old. The use of lipid nanoparticles as biodegradable shells for controlled drug delivery shows promise as a more effective and targeted tumor treatment. However, current techniques for in vitro testing of these vehicles have shown little validity due to their static nature, in which nanoparticles sediment onto the bottom of the wells and kill the cells via asphyxiation, hiding the real effect achieved by the nanoparticles. In this work, a microfluidic platform capable of determining the optimum dose of methotrexate-loaded lipid nanoparticles in osteosarcoma treatment is presented as a promising alternative to current nanoparticle characterization assays. (Author)

Neuropsychological effects of irradiation and chemotherapy treatments upon children with acute lymphoblastic leukemia: a case study of monozygotic twins

International Nuclear Information System (INIS)

Prince, M.T.; Souheaver, G.T.; Berry, D.H.

1988-01-01

Numerous attempts have been made to determine the effects of irradiation and chemotherapy upon cognitive functioning when used for treatment of acute lymphoblastic leukemia (ALL). While many studies have demonstrated a deleterious effect, others have found no significant changes in neuropsychological functioning. The uncertainty regarding the cognitive effects of these treatments is exemplified via a presentation of monozygotic twins who were evaluated via neuropsychological tests. The children received similar induction-consolidation therapy which included intrathecal methotrexate and cranial irradiation. Neuropsychological tests yielded almost identical I.Q. patterns, however, subtle differences were noted between the children when abstract reasoning abilities, achievement tests scores, motor speed, grip strength, performance on complex tasks requiring haptic sensitivity, and fingertip sensitivity were observed. This discussion also summarizes the previous findings related to cognitive function after chemotherapy and radiation therapy and some of the confounding factors which have been noted

Uncommon toxicity of low-dose methotrexate: case report

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Zohreh Yousefi

2015-10-01

Full Text Available Background: Standard treatment of Gestational Trophoblastic Disease (GTD is chemotherapy. Single-agent chemotherapy regime including Methotrexate (MTX or Actinomycin. Single-agent is widely used in treatment of persistent trophoblastic disease. We reported an uncommon toxicity of low-dose single-agent methotrexate in a patient. Case Presentation: A 20-year-old woman, primary gravid after two months missed period and spotting with diagnosis of incomplete abortion with uterine size equivalent of ten weeks pregnancy (8-10 cm underwent evacuation curettage. In serial follow-up, based on rise of beta-hCG titer and absence of metastatic disease, it was categorized as low-risk persistent trophoblastic disease. She was referred to gynecology oncology center of Ghaem Hospital, Mashhad University of Medical Sciences in May 2014. Because of rise of beta-hCG titer, after complete metastatic work-up and lack of disease in other sites, persistent disease was diagnosed and candidate for chemotherapy (single agent low-dose. The patient received first course of therapy with MTX (50 mg/m², intra muscular. Unfortunately, after two days of treatment she developed uncommon severe toxicity, fever, severe nausea and vomiting, tachycardia, and generalized weakness. Also, we found hematologic abnormality (WBC: -14000-15000 µI, platelet- 540 µI and sever neutropenia, and abnormal rising in liver function test (SGOT, SGPT (three to four times and renal function test (BUN and Creatinine (two times. In addition, she had disseminated erosive lesion in all of body especially in face. Due to the fatal side effects of chemotherapy, she was admitted to intensive care unit (ICU. Fortunately, after two to three weeks, she was improved by conservative management. After few weeks beta-hCG titer was in normal limit. However she had normal serial beta-hCG in one year of follow-up. Conclusion: It is important to emphasis unpredictable side effects of chemotherapy with low

Comparison of central nervous system prophylaxis with cranial radiation and intrathecal methotrexate versus intrathecal methotrexate alone in acute lymphoblastic leukemia

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Muriel, F.S.; Svarch, E.; Pavlovsky, S.; Eppinger-Helft, M.; Braier, J.; Vergara, B.; Garay, G.; Kvicala, R.; Divito, J.M.; Failace, R.

1983-08-01

In acute lymphoblastic leukemia, central nervous system prophylaxis with irradiation plus intrathecal methotrexate (i.t. MTX) reduces the incidence of CNS relapse to 7%-15%. However, increased evidence of CNS delayed toxicity was recognized mainly in children as CT scan abnormalities and neuropsychologic alterations. Two questions were analyzed: (1) Will further doses of i.t. methotraxate and dexamethasone (i.t. MTX-DMT) decrease the incidence of CNS relapse. (2) Is i.t. MTX-DMT given during induction and maintenance as effective as cranium irradiation plus i.t. MTX-DMT. Incidence of primary CNS relapse in i.t. MTX-DMT-treated patients with a WBC count < 50,000 and in the untreated group was 11%. In patients with a WBC count > 50,000, it was 16% in the treated group and 19% in the control group. These patients were compared with patients which had received 3 doses of i.t. MTX-DMT alone during induction, 3 doses weekly during the first month of remission, and quarterly thereafter. The incidence of leukemia at 60 mo in patients with a WBC count < 50,000 was 20% in the irradiated group and 32% in the group with i.t. MTX-DMT alone. The relapse-free survival at 60 mo was 26% and 41%, respectively, (p < 0.0005). The incidence in patients with a WBC count > 50,000 at 48 mo was 28% and 42% in the irradiated and nonirradiated group respectively. Complete remission remained at 15% and 16% respectively of patients disease-free at 48 mo. We conclude that (A) after cranial irradiation plus i.t. MTX-DMT X 5, the use of additional doses of i.t. MTX-DMT is not of further benefit in preventing CNS relapse; (B) use of i.t. MTX-DMT alone compares with cranial irradiation plus i.t. MTX-DMT in incidence of CNS relapse; and (C) relapse-free survival and survival in patients with a WBC count < 50.000 were significantly longer in those without cranial irradiation.

Fatal pulmonary fibrosis complicating low dose methotrexate therapy for rheumatoid arthritis

NARCIS (Netherlands)

van der Veen, M. J.; Dekker, J. J.; Dinant, H. J.; van Soesbergen, R. M.; Bijlsma, J. W.

1995-01-01

We report the fatal disease course of 2 aged patients with rheumatoid arthritis (RA). Both had respiratory complaints after 10-15 weeks of treatment with methotrexate (MTX). After withdrawal of MTX, and despite the use of corticosteroids and ventilatory support, both died of respiratory failure.

Methotrexate pharmacogenetics in Uruguayan adults with hematological malignant diseases.

Science.gov (United States)

Giletti, Andrea; Vital, Marcelo; Lorenzo, Mariana; Cardozo, Patricia; Borelli, Gabriel; Gabus, Raúl; Martínez, Lem; Díaz, Lilian; Assar, Rodrigo; Rodriguez, María Noel; Esperón, Patricia

2017-11-15

Individual variability is among the causes of toxicity and interruption of treatment in acute lymphoblastic leukemia (ALL) and severe non-Hodgkin lymphoma (NHL) patients under protocols including Methotrexate (MTX): 2,4-diamino-N10-methyl propyl-glutamic acid. 41 Uruguayan patients were recruited. Gene polymorphisms involved in MTX pathway were analyzed and their association with treatment toxicities and outcome was evaluated. Genotype distribution and allele frequency were determined for SLC19A1 G 80 A, MTHFR C 677 T and A 1298 C, TYMS 28bp copy number variation, SLCO1B1 T 521 C, DHFR C -1610 G/T, DHFR C -680 A, DHFR A -317 G and DHFR 19bp indel. Multivariate analysis showed that DHFR -1610 G/T (OR=0.107, p=0.018) and MTHFR 677 T alleles (OR=0.12, p=0.026) had a strong protective effect against hematologic toxicity, while DHFR -1610 CC genotype increased this toxicity (OR=9, p=0.045). No more associations were found. The associations found between gene polymorphisms and toxicities in this small cohort are encouraging for a more extensive research to gain a better dose individualization in adult ALL and NHL patients. Besides, genotype distribution showed to be different from other populations, reinforcing the idea that genotype data from other populations should not be extrapolated to ours. Copyright © 2017 Elsevier B.V. All rights reserved.

Methotrexate: an effective monotherapy for refractory generalized morphea

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Platsidaki E

2017-05-01

Full Text Available Eftychia Platsidaki, Vassiliki Tzanetakou, Anargyros Kouris, Panagiotis G Stavropoulos Department of Dermatology and Venereology, Andreas Syggros Hospital, University of Athens, Athens, Greece Introduction: Morphea is an inflammatory skin disorder characterized by excessive collagen deposition. Although treatment algorithms for morphea subtypes have been suggested, no consistent recommendations are available. This study attempts to evaluate the clinical efficacy of methotrexate (MTX as monotherapy in refractory generalized morphea. Methods: It is a retrospective study, including 20 patients who had already been treated with various topical and systemic therapies with minimal clinical improvement. Patients received orally MTX at a of dosage 15 mg once weekly. Duration of the use, dosage of MTX, and adverse events were recorded. Clinical assessment of skin lesions was performed and documented. Results: The mean disease duration was 27 months before the initiation of MTX treatment. After 12 months of therapy, very good response was achieved in 6 patients (30%, good response in 10 patients (50%, and fair response in 2 patients (10%, while 2 patients (10% had failed treatment. Patients were followed up for a mean time interval of 21 months. No serious adverse event was recorded. Conclusion: MTX has been already proved to be an effective and well-tolerated treatment in pediatric patients with morphea. The majority of the group of adult patients showed very good and good improvement when treated with MTX. Although this is an uncontrolled study, MTX monotherapy was considered a safe and effective treatment for the management of this specific clinical subset of morphea in adults. Keywords: methotrexate, adults, generalized morphea

Nanoparticles of Conjugated Methotrexate-Human Serum Albumin: Preparation and Cytotoxicity Evaluations

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Azade Taheri

2011-01-01

Full Text Available Methotrexate-human serum albumin conjugates were developed by a simple carbodiimide reaction. Methotrexate-human serum albumin conjugates were then crosslinked with 1-ethyl-3-(3-dimethylaminopropyl carbodiimide HCl (EDC to form nanoparticles. The size of nanoparticles determined by laser light scattering and TEM was between 90–150 nm. Nanoparticles were very stable at physiologic conditions (PBS pH 7.4, 37∘C and after incubation with serum. The effect of amount of EDC used for crosslinking on the particle size and free amino groups of nanoparticles was examined. The amount of crosslinker showed no significant effect on the size of nanoparticles but free amino groups of nanoparticles were decreased by increasing the crosslinker. The physicochemical interactions between methotrexate and human serum albumin were investigated by differential scanning calorimetry (DSC. Nanoparticles were more cytotoxic on T47D cells compared to free methotrexate. Moreover, methotrexate-human serum albumin nanoparticles decreased the IC50 value of methotrexate on T47D cells in comparison with free methotrexate.

Nanoparticles of Conjugated Methotrexate-Human Serum Albumin: Preparation and Cytotoxicity Evaluations

International Nuclear Information System (INIS)

Taheri, A.; Atyabi, F.; Nouri, F.S.; Ahadi, F.; Derakhshan, M.A.; Dinarvand, R.; Atyabi, F.; Ghahremani, M.H.; Ostad, S.N.; Dinarvand, R.; Amini, M.; Ghahremani, M.H.; Ostad, S.N.; Mansoori, P.

2011-01-01

Methotrexate-human serum albumin conjugates were developed by a simple carbodiimide reaction. Methotrexate-human serum albumin conjugates were then crosslinked with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide HCl (EDC) to form nanoparticles. The size of nanoparticles determined by laser light scattering and TEM was between 90 150 nm. Nanoparticles were very stable at physiologic conditions (PBS pH 7.4, 37 degree C) and after incubation with serum. The effect of amount of EDC used for crosslinking on the particle size and free amino groups of nanoparticles was examined. The amount of cross linker showed no significant effect on the size of nanoparticles but free amino groups of nanoparticles were decreased by increasing the cross linker. The physicochemical interactions between methotrexate and human serum albumin were investigated by differential scanning calorimetry (DSC). Nanoparticles were more cytotoxic on T 47 D cells compared to free methotrexate. Moreover, methotrexate-human serum albumin nanoparticles decreased the C50 value of methotrexate on T 47 D cells in comparison with free methotrexate.

Late effects of treatment in survivors of childhood acute lymphoblastic leukaemia

International Nuclear Information System (INIS)

Roux, P.

1987-01-01

The overall aim of this study was a comprehensive assessment of the nature and severity of the late effects of treatment in a group of children surviving acute lymphoblastic leukaemia. In the absence of damage preceding treatment, late effects could be ascribed to treatment. Cranial irradiation, methotrexate, L-asparaginase and cytosine arabinoside are therapeutic modalities most likely to cause injury to the central nervous system. Survivors of childhood leukaemia also showed an increase in weight-for-height during and after therapy which appeared to be the consequence of a loss in statural growth as well as increasing weight-for-age. Assessment of endocrine function in leukaemia survivors indicated abnormalities in the regulation of growth hormone and thyroid stimulating hormone in some patients. Survivors of childhood leukaemia were shown to have an intellectual deficit compared with their siblings and a high incidence of visual-perceptual defects. The intellectual effects of lower doses of cranial irradiation are as yet unknown. A variety of minor neurological abnormalities were detected among leukaemia survivors and thought to be related to preceding central nervous system 'prophylactic' chemotherapy and irradiation. A new instrument, the functional deficit score, was derived to reflect overall outcome in survivors of childhood leukaemia. With few exceptions, leukaemia survivors in this study had received 2400 rads of deep x-ray therapy as cranial irradiation. This dosage has since been reduced world-wide. Current cranial irradiation 'prophylaxis' consists of 1800 rad of megavoltage radiotherapy

Late effects of treatment in survivors of childhood acute lymphoblastic leukaemia

Energy Technology Data Exchange (ETDEWEB)

Roux, P

1987-01-01

The overall aim of this study was a comprehensive assessment of the nature and severity of the late effects of treatment in a group of children surviving acute lymphoblastic leukaemia. In the absence of damage preceding treatment, late effects could be ascribed to treatment. Cranial irradiation, methotrexate, L-asparaginase and cytosine arabinoside are therapeutic modalities most likely to cause injury to the central nervous system. Survivors of childhood leukaemia also showed an increase in weight-for-height during and after therapy which appeared to be the consequence of a loss in statural growth as well as increasing weight-for-age. Assessment of endocrine function in leukaemia survivors indicated abnormalities in the regulation of growth hormone and thyroid stimulating hormone in some patients. Survivors of childhood leukaemia were shown to have an intellectual deficit compared with their siblings and a high incidence of visual-perceptual defects. The intellectual effects of lower doses of cranial irradiation are as yet unknown. A variety of minor neurological abnormalities were detected among leukaemia survivors and thought to be related to preceding central nervous system 'prophylactic' chemotherapy and irradiation. A new instrument, the functional deficit score, was derived to reflect overall outcome in survivors of childhood leukaemia. With few exceptions, leukaemia survivors in this study had received 2400 rads of deep x-ray therapy as cranial irradiation. This dosage has since been reduced world-wide. Current cranial irradiation 'prophylaxis' consists of 1800 rad of megavoltage radiotherapy.

Evaluation of Protective Activity of Curcumin in Reducing Methotrexate Induced Liver Cells Injury: An Experimental Study on Iraqi White Domestic Rabbits

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Hussain Abady Aljebori

2018-03-01

Full Text Available Background: Hepatotoxicity is a common problem in medical practice, most of the commonly used drugs are potentially hepatotoxic. Although Methotrexate is a hepa- toxic drug, it is widely used in the treatment of many cancerous and non-cancerous conditions because of its cytotoxic and immunosuppressant activity. Curcumin con- tains a variety of natural substances with antioxidant properties, it is widely used in  folk medicine.Antioxidant activity of Curcumin can reduce liver cell injury induced by Methotrexate administration. Objective: The research aims to study the methotrexate hepatoxicity on rabbits, and the hepatoprotective activity of Curcumin. Materials and Methods: Thirty white domestic rabbits were bought from animal market and grouped randomly into three groups; control group received intraperitoneal normal saline, methotrexate group received 6.5 mg/Kgm body weight intraperitoneal methotrexate, and curcumin group received oral Curcumin in addition to intraperitoneal methotrexate. Results: The study showed abnormal liver function tests, INR, liver tissues oxida- tive markers, and liver cell injury on histopathology in Methotrexate group, and normal findings in Curcumin groups. Conclusion: It is concluded that the Methotrexate is a hepatotoxic drug. The results also shoe that the concomitant administration of Curcumin reduced hepatotoxicity. Recommendation: It is recommended to use of Curcumin in clinical practice as a food supplement to patient receiving methotrexate to reduce hepatotoxicity.

Selective sparing of goblet cells and paneth cells in the intestine of methotrexate-treated rats

NARCIS (Netherlands)

M. Verburg (Melissa); I.B. Renes (Ingrid); H.P. Meijer; J.A. Taminiau; H.A. Büller (Hans); A.W.C. Einerhand (Sandra); J. Dekker (Jan)

2000-01-01

textabstractProliferation, differentiation, and cell death were studied in small intestinal and colonic epithelia of rats after treatment with methotrexate. Days 1-2 after treatment were characterized by decreased proliferation, increased apoptosis, and decreased numbers and depths

The development of cerebral CT changes during treatment of acute lymphocytic leukemia in childhood

International Nuclear Information System (INIS)

Pedersen, H.; Clausen, N.

1981-01-01

Twenty-three children with acute lymphocytic leukemia (ALL) were examined with cranial CT at least twice with a minimal interval of 10 months. The first CT was performed at the time of diagnosis in 11 children and during therapy in 12; all but two were normal on the first CT examination. These two had slight enlargement of the ventricular system and subarachnoid space at the time of diagnosis. These findings were unchanged on the second CT examinations. Seven patients, all in remission from leukemia of the central nervous system manifested abnormal findings on later CTs. Low density areas in the periventricular white matter were seen in the brains of three, with increasing subcortical calcification in one of these cases. Five children had slight enlargement of the ventricular system and subarachnoid space, especially of the basal and Sylvian cisterns. Later CT examinations in five, plus brain autopsy in two cases, revealed unchanged or progressive conditions. The CT findings have been related to the treatment and some characteristics of the disease. The frequency of CT abnormalities was higher in patients who had received therapeutic irradiation and intraventricular methotrexate treatment. The possible reasons for the CT abnormalities are discussed. (orig.)

Methotrexate for rheumatoid arthritis patients who are on hemodialysis.

Science.gov (United States)

Al-Hasani, Hasanein; Roussou, Euthalia

2011-12-01

Methotrexate (MTX) can be toxic to patients suffering from end stage renal disease (ESRD) on hemodialysis even at low doses. This increase in toxicity is more notable in terms of bone marrow suppression in the form of pancytopenia. Many methods of elimination including dialysis itself have been proven ineffective, and alternate treatments with anti-TNF alpha blockers can be considered.

Growth and puberty after treatment for acute lymphoblastic leukemia

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Alves Claudia Helena Bastos da Silva

2004-01-01

Full Text Available Over the last 20 years, after combining treatment of chemotherapy and radiotherapy, there has been an improvement in the survival rate of acute lymphoblastic leukemia patients, with a current cure rate of around 70%. Children with the disease have been enrolled into international treatment protocols designed to improve survival and minimize the serious irreversible late effects. Our oncology unit uses the international protocol: GBTLI LLA-85 and 90, with the drugs methotrexate, cytosine, arabinoside, dexamethasone, and radiotherapy. However, these treatments can cause gonadal damage and growth impairment. PATIENTS AND METHOD: The authors analyzed 20 children off therapy in order to determine the role of the various doses of radiotherapy regarding endocrinological alterations. They were divided into 3 groups according to central nervous system prophylaxis: Group A underwent chemotherapy, group B underwent chemotherapy plus radiotherapy (18 Gy, and group C underwent chemotherapy plus radiotherapy (24 Gy. Serum concentrations of LH, FSH, GH, and testosterone were determined. Imaging studies included bone age, pelvic ultrasound and scrotum, and skull magnetic resonance imaging. RESULTS: Nine of the patients who received radiotherapy had decreased pituitary volume. There was a significant difference in the response to GH and loss of predicted final stature (Bayley-Pinneau between the 2 irradiated groups and the group that was not irradiated, but there was no difference regarding the radiation doses used (18 or 24 Gy. The final predicted height (Bayley-Pinneau was significantly less (P = 0.0071 in both groups treated with radiotherapy. Two girls had precocious puberty, and 1 boy with delayed puberty presented calcification of the epididymis. CONCLUSION: Radiotherapy was been responsible for late side effects, especially related to growth and puberty.

EFFICACY OF DIFFERENT IMMUNOSUPPRESSIVE PROTOCOLS WITH CYCLOSPORINE AND METHOTREXATE FOR PATIENTS WITH SYSTEMIC VARIANT OF JUVENILE RHEUMATOID ARTHRITIS

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E.I. Alexeeva

2007-01-01

Full Text Available The article provides information on efficiency of different protocols of therapy with cyclosporine and methotrexate for patients suffering from severe systemic juvenile rheumatoid arthritis (JRA. it shows that a therapy combining cyclosporine with dosage of 4,4 ± 0,58 mg/kg of body per day and methotrexate with dosage of 8,1 ± 1,07 mg/m2 a week is more efficient than monotherapy with each of the same medications of same dosage. Combined use of immunosuppressants induces remission of articular syndrome and constitutional manifestations, as well as provides normalization of laboratory disease activity indications in more than 50% of cases of long clasting systemic variant of JRA on the average a year after the initiation of treatment. Combining cyclosporine with methotrexat improves the curative action of each of the medications without aggravation of their toxic influence. High efficiency of combining cyclosporine with methotrexate makes enables lowering the dosage of glucocorticoids to be taken orally, as well as not prescribing prednisolone to the severe cases of systemic variant of JRA.Key words: juvenile rheumatoid arthritis, treatment, cyclosporine, methotrexate, combined therapy, children.

An animal model to study toxicity of central nervous system therapy for childhood acute lymphoblastic leukemia: Effects on behavior

International Nuclear Information System (INIS)

Mullenix, P.J.; Kernan, W.J.; Tassinari, M.S.; Schunior, A.; Waber, D.P.; Howes, A.; Tarbell, N.J.

1990-01-01

Central nervous system prophylactic therapy used in the treatment of acute lymphoblastic leukemia can reduce intelligence quotient scores and impair memory and attention in children. Cranial irradiation, intrathecal methotrexate, and steroids are commonly utilized in acute lymphoblastic leukemia therapy. How they induce neurotoxicity is unknown. This study employs an animal model to explore the induction of neurotoxicity. Male and female Sprague-Dawley rats at 17 and 18 days of age were administered 18 mg/kg prednisolone, 2 mg/kg methotrexate, and 1000 cGy cranial irradiation. Another 18-day-old group was administered 1000 cGy cranial irradiation but no drugs. Matching controls received saline and/or a sham exposure to radiation. All animals at 6 weeks and 4 months of age were tested for alterations in spontaneous behavior. A computer pattern recognition system automatically recorded and classified individual behavioral acts displayed during exploration of a novel environment. Measures of behavioral initiations, total time, and time structure were used to compare treated and control animals. A permanent sex-specific change in the time structure of behavior was induced by the prednisolone, methotrexate, and radiation treatment but not by radiation alone. Unlike hyperactivity, the effect consisted of abnormal clustering and dispersion of acts in a pattern indicative of disrupted development of sexually dimorphic behavior. This study demonstrates the feasibility of an animal model delineating the agent/agents responsible for the neurotoxicity of central nervous system prophylactic therapy

Methotrexate-induced toxicity pharmacogenetics: an umbrella review of systematic reviews and meta-analyses.

Science.gov (United States)

Campbell, Jared M; Bateman, Emma; Stephenson, Matthew D; Bowen, Joanne M; Keefe, Dorothy M; Peters, Micah D J

2016-07-01

Methotrexate chemotherapy is associated with various toxicities which can result in the interruption or discontinuation of treatment and a subsequently raised risk of relapse. This umbrella systematic review was conducted to synthesize the results of all existing systematic reviews that investigate the pharmacogenetics of methotrexate-induced toxicity, with the aim of developing a comprehensive reference for personalized medicine. Databases searched were PubMed, Embase, JBI Database of Systematic Reviews and Implementation Reports, DARE, and ProQuest. Papers were critically appraised by two reviewers, and data were extracted using a standardized tool. Three systematic reviews on methotrexate-induced toxicity were included in the review. Meta-analyses were reported across Asian, Caucasian, pediatric and adult patients for the MTHFR C677T and A1298C polymorphisms. Toxicity outcomes included different forms of hematologic, ectodermal and hepatic toxicities. Results varied considerably depending on the patient groups and subgroups investigated in the different systematic reviews, as well as the genetic models utilized. However, significant associations were found between the MTHFR C677T allele and; hepatic toxicity, myelosuppression, oral mucositis, gastrointestinal toxicity, and skin toxicity. Additionally, limited evidence suggests that the MTHFR A1298C polymorphism may be associated with decreased risk of skin toxicity and leukopenia. This umbrella systematic review has synthesized the best available evidence on the pharmacogenetics of methotrexate toxicity. The next step in making personalized medicine for methotrexate therapy a clinical reality is research on the effectiveness and cost-effectiveness of MTHFR genotype testing to enable the close monitoring of at-risk patients for the timely initiation of rescue therapies.

Dynamics of Destructive Joint Changes in Juvenile Idiopathic Arthritis in Children who Received Methotrexate or Methotrexate-Tocilizumab Combination: a Cohort Study

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Maria A. Davydova

2017-01-01

Full Text Available Background. Destructive joint damages in juvenile arthritis inevitably lead to persistent disability in adulthood. These consequences can be avoided by resorting to early therapy of the disease.Objective. Our aim was to assess the dynamics of destructive joint changes in juvenile idiopathic arthritis (JIA in children, depending on a basic therapy.Methods. We studied the treatment results of children with systemic-onset JIA with active joint syndrome without active  systemic manifestations hospitalized in the regional clinical  cardiological health center. JIA activity criteria at the time of  hospitalization: 3 joints with active arthritis; the assessment of the disease activity by a doctor 3 points out of 10; the assessment of  wellbeing by the patient or a parent 3 points out of 10; the  appointment of basic therapy no later than 6 months from the  disease onset. Treatment results were compared in the groups of  methotrexate (hospitalization from January 2008 to December 2010 and methotrexate + tocilizumab (January 2014 — September 2016. The main outcome of JIA therapy was the severity of joint  destruction in 6, 12 and 24 months as determined by the modified  Sharpe ratio according to radiographs obtained from patients' medical records.Results. The study groups were comparable in terms of sex and age of the patients, JIA onset age, the disease activity at the time of  hospitalization, and the initial assessment of joint destruction —  (median 165 (131; 187 and 162 (124; 171 (p = 0.116. Under  pressure of therapy, the modified Sharpe score in the group of  methotrexate monotherapy was higher than in the group of combined therapy: in 6 months — 142 (126; 163 and 87 (72; 112 (p < 0.001; in 12 months — 166 (121; 210 and 75 (29; 89 (p <  0.001; in 24 months — 165 (113; 198 and 52 (26; 73 (p <  0.001. At the first administration of tocilizumab, 4 children had nausea and abdominal pain, and 3 children had

Can the Methotrexate Therapy Prevent the Development of Uveitis in Patients with Juvenile Idiopathic Arthritis: Results of a Retrospective Study

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M. M. Kostik

2015-01-01

Full Text Available Background: Uveitis is one of the most common extra-articular manifestations of juvenile idiopathic arthritis (JIA. Currently, the possibility of reducing the risk of uveitis in children with JIA by using methotrexate has been studied.Objective: Our aim was to analyze the results of treatment of children with JIA by studying the relation between the use of methotrexate and the risk of uveitis.Methods: A retrospective uncontrolled study. The case histories of patients with JIA who were treated for at least 2 years after the onset of the disease were studied. The results of treatment of patients who received and who did not receive methotrexate were studied (standard therapy — non-steroidal anti-inflammatory drugs and intra-articular injections of glucocorticoids. The established cases of uveitis were taken into account.Results: The study analyzed the results of observation of 281 children with JIA. In the methotrexate group, uveitis was detected in 22/191 (11.5%, and in the control group — in 42/90 (46.7% of patients (OR 6.7; 95% CI 3.7–12.3. The time period between the onset of JIA and development of uveitis in two groups under study was the same and equal to 24 (12; 67 and 17 months (7; 35, respectively (p = 0.232. Multivariate regression analysis showed that the main predictors of uveitis were oligoarticular course of JIA (HR = 1.89, positive antinuclear antibody test (HR = 2.14, onset of JIA under the age of 5 (HR = 2.56, female gender (HR = 1.82,and the absence of methotrexate in the therapy (HR = 0.24.Conclusion: The treatment with methotrexate may reduce the risk of uveitis in patients with JIA. To confirm this hypothesis, randomized studies are needed.

Methotrexate and Pregnancy

Science.gov (United States)

... increased risk for infertility, not birth defects. Low sperm count has been seen in some men using methotrexate. Most of these men were using high doses of the medication, as well as other medications used to treat cancer. Sperm levels returned to normal after the men stopped ...

Comparison of weakness progression in inclusion body myositis during treatment with methotrexate or placebo

NARCIS (Netherlands)

Badrising, UA; Maat-Schieman, MLC; Ferrari, MD; Zwinderman, AH; Wessels, JAM; Breedveld, FC; van Doorn, PA; van Engelen, BGM; Hoogendijk, JE; Howeler, CJ; de Jager, AE; Jennekens, FGI; Koehler, PJ; de Visser, M; Viddeleer, A; Verschuuren, JJ; Wintzen, AR

We investigated whether 5 to 20mg per week oral methotrexate could slow down disease progression in 44 patients with inclusion body myositis in a randomized double-blind placebo-controlled study over 48 weeks. Mean change of quantitative muscle strength testing sum scores was the primary study

Chromatic response of polydiacetylene vesicle induced by the permeation of methotrexate.

Science.gov (United States)

Shin, Min Jae; Kim, Ye Jin; Kim, Jong-Duk

2015-07-07

The noble vesicular system of polydiacetylene showed a red shift using two types of detecting systems. One of the systems involves the absorption of target materials from the outer side of the vesicle, and the other system involves the permeation through the vesicular layers from within the vesicle. The chromatic mixed vesicles of N-(2-aminoethyl)pentacosa-10,12-diynamide (AEPCDA) and dimethyldioctadecylammonium chloride (DODAC) were fabricated by sonication, followed by polymerization by UV irradiation. The stability of monomeric vesicles was observed to increase with the polymerization of the vesicles. Methotrexate was used as a target material. The polymerized mixed vesicles having a blue color were exposed to a concentration gradient of methotrexate, and a red shift was observed indicating the adsorption of methotrexate on the polydiacetylene bilayer. In order to check the chromatic change by the permeation of methotrexate, we separated the vesicle portion, which contained methotrexate inside the vesicle, and checked chromatic change during the permeation of methotrexate through the vesicle. The red shift apparently indicates the disturbance in the bilayer induced by the permeation of methotrexate. The maximum contrast of color appeared at the equal molar ratio of AEPCDA and DODAC, indicating that the formation of flexible and deformable vesicular layers is important for red shift. Therefore, it is hypothesized that the system can be applicable for the chromatic detection of the permeation of methotrexate through the polydiacetylene layer.

Overview and guidelines of off-label use of methotrexate in ectopic pregnancy: report by CNGOF.

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Marret, Henri; Fauconnier, Arnaud; Dubernard, Gil; Misme, Hélène; Lagarce, Laurence; Lesavre, Magali; Fernandez, Hervé; Mimoun, Camille; Tourette, Claire; Curinier, Sandra; Rabishong, Benoit; Agostini, Aubert

2016-10-01

Our objective is to describe off-label use of methotrexate in ectopic pregnancy treatment using evidence based medicine. The patient group includes all women with a pregnancy outside the usual endometrium, or of unknown location. Method used was a Medline search on ectopic pregnancy managed using methotrexate treatment; evidence synthesis was done based on this current literature analysis. Level of evidence (LE) were given according to the centre for evidence base medicine rules. Grade was proposed for guidelines but no recommendation was possible as misoprostol is off label use for all the indications studied. In the absence of any contraindication, the protocol recommended for medical treatment of ectopic pregnancy is a single intramuscular injection of methotrexate (MTX) at a dosage of 1mg/kg or 50mg/m(2) (Grade A). It can be repeated once at the same dose should the hCG concentration not fall sufficiently. Pretreatment laboratory results must include a complete blood count and kidney and liver function tests (in accordance with its marketing authorization). MTX is an alternative to conservative treatment such as laparoscopic salpingotomy for uncomplicated tubal pregnancy (Grade A) with pretreatment hCG levels≤5000IU/l (Grade B). Expectant management is preferred for hCG levelslocation persisting more than 10days in an asymptomatic woman who has an hCG level>2000IU/l, routine MTX treatment is an option. MTX is not indicated for combination with treatments such as mifepristone or potassium. Copyright © 2016. Published by Elsevier Ireland Ltd.

Methotrexate-induced nonhealing cutaneous ulcers in a nonpsoriatic patient without pancytopenia

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Venkatesh Krishnamurthy Tekur

2016-01-01

Full Text Available Methotrexate forms one of the main drugs in the pharmacological management of rheumatoid arthritis, psoriasis, and some neoplastic diseases. Methotrexate rarely causes cutaneous ulceration and most cases are reported in patients with psoriasis and have been accompanied by pancytopenia. The author here reports occurrence of multiple (two cutaneous ulcers due to methotrexate in a nonpsoriatic patient. The patient was on methotrexate for seronegative rheumatoid arthritis for 10 years. To the best of the Author's knowledge, this is a rare case of cutaneous ulceration due to methotrexate in a nonpsoriatic patient reported in the literature so far, and probably one of its kind without pancytopenia or other hematological abnormalities. Stopping this medication led to complete healing of the ulcerated lesion in about four to six weeks.

Tocilizumab-Induced Acute Liver Injury in Adult Onset Still’s Disease

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Michael Drepper

2013-01-01

Full Text Available Background. Tocilizumab, a monoclonal humanized anti-IL-6 receptor antibody, is used in treatment of refractory adult onset Still’s disease (AOSD. Mild to moderate liver enzyme elevation is a well-known side effect, but severe liver injury has only been reported in 3 cases in the literature. Case. A young female suffering from corticoid and methotrexate refractory AOSD was treated by tocilizumab. After 19 months of consecutive treatment, she developed acute severe liver injury. Liver biopsy showed extensive hepatocellular necrosis with ballooned hepatocytes, highly suggestive of drug-induced liver injury. No other relevant drug exposure beside tocilizumab was recorded. She recovered totally after treatment discontinuation and an initial 3-day course of intravenous N-acetylcysteine with normalization of liver function tests after 6 weeks. Conclusion. Acute severe hepatitis can be associated with tocilizumab as documented in this case. Careful monitoring of liver function tests is warranted during tocilizumab treatment.

Optimal treatment of acute cholecystitis

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Loozen, C.S.

2017-01-01

The studies presented in this thesis focus on two main issues: treatment strategies for acute calculous cholecystitis (Part I), and the management of acute calculous cholecystitis in high-risk patients in particular (Part II). The last chapter focuses on the surgical treatment of common bile duct

Myometrial Cystic Formation after Local Methotrexate Application into Cornual Gestational Sac: A Case Report of an Unexpected Complication

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Zehra Sema Ozkan

2011-01-01

Full Text Available Cornual pregnancy is a rare type of ectopic pregnancy, and diverse therapeutic options exist for the management. Medical treatment despite high initial beta HCG values is not thought to be safe. We reported a 39-year-old woman with an initial beta HCG value of 22000 mIU/mL and diagnosed of a cornual pregnancy. Patient was managed successfully with the administration of combined systemic and ultrasonographically guided local injection of methotrexate into the gestational sac. During followup with serial beta hcg measurements, 27×20 mm cystic area in myometrium has been detected. Beta hcg <1 mIU/mL value was reached three months later, and this cystic area resolved spontaneously. Systemic methotrexate administration combined with ultrasound-guided local methotrexate injection into the gestational sac might be considered as the first-line treatment in the management of hemodynamically stable patients having cornual pregnancy even with high beta HCG values and risk of myometrial cystic formation.

Influence of pre-hydration and pharmacogenetics on plasma methotrexate concentration and renal dysfunction following high-dose methotrexate therapy.

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Yanagimachi, Masakatsu; Goto, Hiroaki; Kaneko, Tetsuji; Naruto, Takuya; Sasaki, Koji; Takeuchi, Masanobu; Tanoshima, Reo; Kato, Hiromi; Yokosuka, Tomoko; Kajiwara, Ryosuke; Fujii, Hisaki; Tanaka, Fumiko; Goto, Shoko; Takahashi, Hiroyuki; Mori, Masaaki; Kai, Sumio; Yokota, Shumpei

2013-12-01

High-dose methotrexate therapy (HD-MTX) has been well established for the treatment of childhood acute lymphoblastic leukemia (ALL). The aims of this study were to investigate whether clinical and pharmacogenetic factors influence plasma MTX concentration and renal dysfunction in patients treated with HD-MTX. In a total of 127 courses of HD-MTX in 51 patients with childhood ALL, influence of clinical and pharmacogenetic factors on plasma MTX concentration and HD-MTX-related renal dysfunction was evaluated. Clinical factors included age, gender, duration of HD-MTX continuous-infusion and duration of pre-hydration before HD-MTX. Pharmacogenetic factors included 5 gene polymorphisms within the MTX pathway genes, namely, SLC19A1, MTHFR, ABCC2 and ABCG2. Short duration of pre-hydration before HD-MTX is the most important risk factor for prolonged high MTX concentration (p < 0.001, OR 6.40, 95 % CI 2.39-17.16) and renal dysfunction (p = 0.013, OR 3.15, 95 % CI 1.27-7.80). The T allele at MTHFR C677T was the risk factor for prolonged high MTX concentration (p = 0.009, OR 5.54, 95 % CI 1.54-19.85), but not for renal dysfunction. We found the influence of MTHFR C677T polymorphism on prolonged high MTX concentration. We reconfirmed the importance of adequate pre-hydration before HD-MTX to prevent prolonged high MTX concentration and MTX-related renal dysfunction.

Adalimumab plus Methotrexate for Uveitis in Juvenile Idiopathic Arthritis.

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Ramanan, Athimalaipet V; Dick, Andrew D; Jones, Ashley P; McKay, Andrew; Williamson, Paula R; Compeyrot-Lacassagne, Sandrine; Hardwick, Ben; Hickey, Helen; Hughes, Dyfrig; Woo, Patricia; Benton, Diana; Edelsten, Clive; Beresford, Michael W

2017-04-27

Adalimumab, a fully human anti-tumor necrosis factor α monoclonal antibody, is effective in the treatment of juvenile idiopathic arthritis (JIA). We tested the efficacy of adalimumab in the treatment of JIA-associated uveitis. In this multicenter, double-blind, randomized, placebo-controlled trial, we assessed the efficacy and safety of adalimumab in children and adolescents 2 years of age or older who had active JIA-associated uveitis. Patients who were taking a stable dose of methotrexate were randomly assigned in a 2:1 ratio to receive either adalimumab (at a dose of 20 mg or 40 mg, according to body weight) or placebo, administered subcutaneously every 2 weeks. Patients continued the trial regimen until treatment failure or until 18 months had elapsed. They were followed for up to 2 years after randomization. The primary end point was the time to treatment failure, defined according to a multicomponent intraocular inflammation score that was based on the Standardization of Uveitis Nomenclature criteria. The prespecified stopping criteria were met after the enrollment of 90 of 114 patients. We observed 16 treatment failures in 60 patients (27%) in the adalimumab group versus 18 treatment failures in 30 patients (60%) in the placebo group (hazard ratio, 0.25; 95% confidence interval [CI], 0.12 to 0.49; Ptreatment failure than placebo among children and adolescents with active JIA-associated uveitis who were taking a stable dose of methotrexate. Patients who received adalimumab had a much higher incidence of adverse events and serious adverse events than those who received placebo. (Funded by the NIHR Health Technology Assessment Programme and Arthritis Research UK; SYCAMORE EudraCT number, 2010-021141-41 .).

Frequency of methotrexate intolerance in rheumatoid arthritis patients using methotrexate intolerance severity score (MISS questionnaire).

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Fatimah, Nibah; Salim, Babur; Nasim, Amjad; Hussain, Kamran; Gul, Harris; Niazi, Sarah

2016-05-01

The objective of the study was to determine the frequency of methotrexate intolerance in rheumatoid arthritis (RA) patients by applying the methotrexate intolerance severity score (MISS) questionnaire and to see the effect of dose and concomitant use of other disease-modifying antirheumatic drugs (DMARDS) on methotrexate (MTX) intolerance. For the descriptive study, non-probability sampling was carried out in the Female Rheumatology Department of Fauji Foundation Hospital (FFH), Rawalpindi, Pakistan. One hundred and fifty diagnosed cases of RA using oral MTX were selected. The MISS questionnaire embodies five elements: abdominal pain, nausea, vomiting, fatigue and behavioural symptoms. The amplitude of each element was ranked from 0 to 3 being no complaint (0 points), mild (1 point), moderate (2 points) and severe (3 points). A cut-off score of 6 and above ascertained intolerance by the physicians. A total of 33.3 % of the subjects exhibited MTX intolerance according to the MISS questionnaire. Out of which, the most recurring symptom of all was behavioural with a value of 44 % whereas vomiting was least noticeable with a figure of 11 %. About 6.6 % of the women with intolerance were consuming DMARDs in conjunction with MTX. Those using the highest weekly dose of MTX (20 mg) had supreme intolerance with prevalence in 46.2 % of the patients. The frequency of intolerance decreased with a decrease in weekly dose to a minimum of 20 % with 7.5 mg of MTX. MTX intolerance has moderate prevalence in RA patients and if left undetected, the compliance to use of MTX as a first-line therapy will decrease. Methotrexate intolerance is directly proportional to the dose of MTX taken. Also, there is no upstroke seen in intolerance with the use of other disease-modifying agents.

Targeting TNF-α and NF-κB activation by bee venom: role in suppressing adjuvant induced arthritis and methotrexate hepatotoxicity in rats.

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Darwish, Samar F; El-Bakly, Wesam M; Arafa, Hossam M; El-Demerdash, Ebtehal

2013-01-01

Low dose methotrexate is the cornerstone for the treatment of rheumatoid arthritis. One of its major drawbacks is hepatotoxicity, resulting in poor compliance of therapy. Dissatisfied arthritis patients are likely to seek the option of complementary and alternative medicine such as bee venom. The combination of natural products with modern medicine poses the possibility of potential interaction between the two groups and needs investigation. The present study was aimed to investigate the modulatory effect of bee venom acupuncture on efficacy, toxicity, and pharmacokinetics and tissue disposition of methotrexate. Complete Freund's adjuvant induced arthritic rats were treated for 3 weeks with methotrexate and/or bee venom. Arthritic score, ankle diameter, paw volume and tissue expression of NF-κB and TNF-α were determined to assess anti-arthritic effects, while anti-nociceptive effects were assessed by gait score and thermal hyperalgesia. Methotrexate toxicity was assessed by measuring serum TNF-α, liver enzymes and expression of NF-κB in liver. Combination therapy of bee venom with methotrexate significantly improved arthritic parameters and analgesic effect as compared to methotrexate alone. Bee venom ameliorated serum TNF-α and liver enzymes elevations as well as over expression of NF-κB in liver induced by methotrexate. Histological examination supported the results. And for the first time bee venom acupuncture was approved to increase methotrexate bioavailability with a significant decrease in its elimination. bee venom potentiates the anti-arthritic effects of methotrexate, possibly by increasing its bioavailability. Also, it provides a potent anti-nociceptive effect. Furthermore, bee venom protects against methotrexate induced hepatotoxicity mostly due to its inhibitory effect on TNF-α and NF-κB.

Plasma MicroRNA Profiles in Patients with Early Rheumatoid Arthritis Responding to Adalimumab plus Methotrexate vs Methotrexate Alone

DEFF Research Database (Denmark)

Sode, Jacob; Krintel, Sophine B; Carlsen, Anting Liu

2018-01-01

OBJECTIVE: The aim was to identify plasma (i.e., cell-free) microRNA (miRNA) predicting antitumor necrosis and/or methotrexate (MTX) treatment response in patients enrolled in an investigator-initiated, prospective, double-blinded, placebo-controlled trial (The OPERA study, NCT00660647). METHODS......: We included 180 disease-modifying antirheumatic drug-naive patients with early rheumatoid arthritis (RA) randomized to adalimumab (ADA; n = 89) or placebo (n = 91) in combination with MTX. Plasma samples before and 3 months after treatment initiation were analyzed for 91 specific mi...... multivariate miRNA models were able to predict response to ADA treatment after 3 and 12 months, with 63% and 82% area under the ROC curves, respectively. CONCLUSION: We identified miR-27a-3p as a potential predictive biomarker of ACR/EULAR remission in patients with early RA treated with ADA in combination...

Acute treatment of migraine headaches.

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Taylor, Frederick R

2010-04-01

Optimum acute treatment of migraine requires prevention of headache as a top priority. Recognition of the multitude of migraine presentations, the frequency of total headache attacks, and number of days of headache disability are critical. Successful treatment requires excellent patient-clinician communication enhancing confidence and mutual trust based on patient needs and preferences. Optimum management of acute migraine nearly always requires pharmacologic treatment for rapid resolution. Migraine-specific triptans, dihydroergotamine, and several antiinflammatories have substantial empirical clinical efficacy. Older nonspecific drugs, particularly butalbital and opioids, contribute to medication overuse headache and are to be avoided. Clinicians should utilize evidence-based acute migraine-specific therapy stressing the imperative acute treatment goal of early intervention, but not too often with the correct drug, formulation, and dose. This therapy needs to provide cost-effective fast results, meaningful to the patient while minimizing the need for additional drugs. Migraine-ACT evaluates 2-hour pain freedom with return to normal function, comfort with treatment, and consistency of response. Employ a thoroughly educated patient, formulary, testimonials, stratification, and rational cotherapy against the race to central sensitization for optimum outcomes. Thieme Medical Publishers.

Uterine Artery Embolization Combined with Local Methotrexate and Systemic Methotrexate for Treatment of Cesarean Scar Pregnancy with Different Ultrasonographic Pattern

International Nuclear Information System (INIS)

Lian Fan; Wang Yu; Chen Wei; Li Jiaping; Zhan Zhongping; Ye Yujin; Zhu, Yunxiao; Huang Jia; Xu Hanshi; Yang Xiuyan; Liang Liuqin; Yang Jianyong

2012-01-01

Purpose: This study was designed to compare the effectiveness of systemic methotrexate (MTX) with uterine artery embolization (UAE) combined with local MTX for the treatment of cesarean scar pregnancy (CSP) with different ultrasonographic pattern, and to indicate the preferable therapy in CSP patients. Methods: The results of 21 CSP cases were reviewed. All subjects were initially administrated with systemic MTX (50 mg/m 2 body surface area). UAE combined with local MTX was added to the patients who had failed systemic MTX. The transvaginal ultrasonography data were retrospectively assessed, and two different ultrasonographic patterns were found: surface implantation and deep implantation of amniotic sac. The management and its effectiveness for patients with the two ultrasonographic patterns were studied retrospectively. Ultrasound scan and serum β-hCG were monitored during follow-up. Data were analyzed with the Student’s t test. Results: Nine patients were successfully treated with systemic MTX. The remaining 12 cases were successfully treated with additional UAE combined with local MTX. According to the classification by Vial et al. of CSP on ultrasonography, most surface implanted CSPs (8/11, 72.7%) could be successfully treated with systemic MTX, whereas most deeply implanted CSPs (9/10, 90%) had failed systemic MTX but still could be successfully treated with additional UAE combined with local MTX. All patients recovered without severe side effects. Most patients with a future desire for reproduction achieved subsequent pregnancy. Conclusions: For CSP patients suitable for nonsurgical treatment, UAE combined with local MTX would be the superior option compared with systemic MTX in the cases with deep implantation of amniotic sac.

Treatment of severe acute pancreatitis

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Praznik Ivan

2014-01-01

Full Text Available Acute pancreatitis is an acute inflammatory process of the pancreas with variable involvement of other regional tissues or other organ systems. The severe form of the disease occurs in 10-20% of cases, and usually requires prolonged hospitalization due to a frequent local and systemic complications. Additionally, considerable mortality despite diagnostic and therapeutic advances, makes this disease a serious health problem nowadays. The aim of this study was to conduct a review of randomized controlled trials to determine differences in the efficiency between standard methods of treatment for severe acute pancreatitis and new treatment ways in terms of decreased mortality. Search of the 'Medline' database of original scientific papers and systematic review articles was made, using a combination of the following keywords: acute pancreatitis, treatment, mortality. In total 914 papers were found, published in the last 13 years; 14 of 64 randomized controlled clinical trials met the selection criteria and were eligible for inclusion. From a total of 16 papers, the conservative treatment was related to 11, which includes some of the new treatment methods, while the effects of new methods of treatment have been the subject of research in the four studies. Combined endoscopic and surgical treatment was applied in only one study. The largest sample of 290 patients was included in the study with platelet activation factor antagonist, while the smallest sample of 22 patients was used in the study that compared total parenteral with enteral nutrition. Continuous regional arterial infusion of protease inhibitors in combination with antibiotics, intravenous supplementation of alanyl-glutamine dipeptide and the early, high-volume continuous veno-venous hemofiltration showed the best results in the treatment of patients with severe acute pancreatitis. Also, the use of low molecular weight heparin and enteral nutrition significantly reduced mortality.

The Promise of Pharmacogenomics in Reducing Toxicity During Acute Lymphoblastic Leukemia Maintenance Treatment

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Shoshana Rudin

2017-04-01

Full Text Available Pediatric acute lymphoblastic leukemia (ALL affects a substantial number of children every year and requires a long and rigorous course of chemotherapy treatments in three stages, with the longest phase, the maintenance phase, lasting 2–3 years. While the primary drugs used in the maintenance phase, 6-mercaptopurine (6-MP and methotrexate (MTX, are necessary for decreasing risk of relapse, they also have potentially serious toxicities, including myelosuppression, which may be life-threatening, and gastrointestinal toxicity. For both drugs, pharmacogenomic factors have been identified that could explain a large amount of the variance in toxicity between patients, and may serve as effective predictors of toxicity during the maintenance phase of ALL treatment. 6-MP toxicity is associated with polymorphisms in the genes encoding thiopurine methyltransferase (TPMT, nudix hydrolase 15 (NUDT15, and potentially inosine triphosphatase (ITPA, which vary between ethnic groups. Moreover, MTX toxicity is associated with polymorphisms in genes encoding solute carrier organic anion transporter family member 1B1 (SLCO1B1 and dihydrofolate reductase (DHFR. Additional polymorphisms potentially associated with toxicities for MTX have also been identified, including those in the genes encoding solute carrier family 19 member 1 (SLC19A1 and thymidylate synthetase (TYMS, but their contributions have not yet been well quantified. It is clear that pharmacogenomics should be incorporated as a dosage-calibrating tool in pediatric ALL treatment in order to predict and minimize the occurrence of serious toxicities for these patients.

Serum creatinine and creatinine clearance for predicting plasma methotrexate concentrations after high-dose methotrexate chemotherapy for the treatment for childhood lymphoblastic malignancies.

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Xu, Wei-qun; Zhang, Ling-yan; Chen, Xue-ying; Pan, Bin-hua; Mao, Jun-qing; Song, Hua; Li, Jing-yuang; Tang, Yong-min

2014-01-01

Monitoring of plasma methotrexate (MTX) concentrations allows for therapeutic adjustments in treating childhood acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL) with high-dose MTX (HDMTX). We tested the hypothesis that assessment of creatinine clearance (CrCl) and/or serum Cr may be a suitable means of monitoring plasma MTX concentrations. All children in the study had ALL or NHL, were in complete remission, and received HDMTX (3 or 5 g/m(2))+leucovorin. Plasma MTX concentrations were measured at 24, 48, and 96 h. CrCl was determined at 24 and 48 h. Correlations between 24- and 48-h plasma MTX concentrations and CrCl and serum Cr concentrations were determined. CrCl and serum Cr concentrations were compared over time between children who had delayed and non-delayed MTX elimination. A total of 105 children were included. There were significant negative correlations between CrCl at 24 and 48 h and plasma MTX concentrations at 24 (both p < 0.001) and 48 h (both p < 0.001). There were significant positive correlations between serum Cr concentrations at both 24 and 48 h and plasma MTX concentrations at 24 (both p < 0.001) and 48 h (both p < 0.001). There were 88 (30.2 %) instances of elimination delay. Children with elimination delay had significantly lower CrCl and higher Cr concentrations at 24 and 48 h compared with children without elimination delay (all p < 0.05). Our findings suggest that, with further refinement, assessment of renal function may be a useful means of monitoring plasma MTX concentrations during HDMTX for ALL and NHL.

Taurine protects against methotrexate-induced toxicity and inhibits leukocyte death

International Nuclear Information System (INIS)

Cetiner, Mustafa; Sener, Goeksel; Sehirli, A. Ozer; Eksioglu-Demiralp, Emel; Ercan, Feriha; Sirvanci, Serap; Gedik, Nursal; Akpulat, Sertac; Tecimer, Tuelay; Yegen, Berrak C.

2005-01-01

The efficacy of methotrexate (MTX), a widely used cytotoxic chemotherapeutic agent, is often limited by severe side effects and toxic sequelae. Regarding the mechanisms of these side effects, several hypotheses have been put forward, among which oxidative stress is noticeable. The present study was undertaken to determine whether taurine, a potent free radical scavenger, could ameliorate MTX-induced oxidative injury and modulate immune response. Following a single dose of methotrexate (20 mg/kg), either saline or taurine (50 mg/kg) was administered for 5 days. After decapitation of the rats, trunk blood was obtained and the ileum, liver, and kidney were removed to measure malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity, and collagen content, as well as histological examination. Our results showed that MTX administration increased the MDA, MPO activity, and collagen contents and decreased GSH levels in all tissues (P < 0.001), while these alterations were reversed in taurine-treated group (P < 0.05-0.01). Elevated (P < 0.001) TNF-α level observed following MTX treatment was depressed with taurine (P < 0.01). Oxidative burst of neutrophils stimulated by phorbol myristate acetate was reduced in saline-treated MTX group (P < 0.001), while taurine abolished this effect. Similarly, flow cytometric measurements revealed that leukocyte apoptosis and cell death were increased in MTX-treated animals, while taurine reversed these effects (P < 0.05). Reduced cellularity in bone marrow samples of MTX-treated group (P < 0.01) was reversed back to control levels in taurine-treated rats. Severe degeneration of the intestinal mucosa, liver parenchyma, glomerular, and tubular epithelium observed in saline-treated group was improved by taurine treatment. In conclusion, it appears that taurine protects against methotrexate-induced oxidant organ injury and inhibits leukocyte apoptosis and may be of therapeutic potential in alleviating the systemic

Curcumin and folic acid abrogated methotrexate induced vascular endothelial dysfunction.

Science.gov (United States)

Sankrityayan, Himanshu; Majumdar, Anuradha S

2016-01-01

Methotrexate, an antifolate drug widely used in rheumatoid arthritis, psoriasis, and cancer, is known to cause vascular endothelial dysfunction by causing hyperhomocysteinemia, direct injury to endothelium or by increasing the oxidative stress (raising levels of 7,8-dihydrobiopterin). Curcumin is a naturally occurring polyphenol with strong antioxidant and anti-inflammatory action and therapeutic spectra similar to that of methotrexate. This study was performed to evaluate the effects of curcumin on methotrexate induced vascular endothelial dysfunction and also compare its effect with that produced by folic acid (0.072 μg·g(-1)·day(-1), p.o., 2 weeks) per se and in combination. Male Wistar rats were exposed to methotrexate (0.35 mg·kg(-1)·day(-1), i.p.) for 2 weeks to induce endothelial dysfunction. Methotrexate exposure led to shedding of endothelium, decreased vascular reactivity, increased oxidative stress, decreased serum nitrite levels, and increase in aortic collagen deposition. Curcumin (200 mg·kg(-1)·day(-1) and 400 mg·kg(-1)·day(-1), p.o.) for 4 weeks prevented the increase in oxidative stress, decrease in serum nitrite, aortic collagen deposition, and also vascular reactivity. The effects were comparable with those produced by folic acid therapy. The study shows that curcumin, when concomitantly administered with methotrexate, abrogated its vascular side effects by preventing an increase in oxidative stress and abating any reduction in physiological nitric oxide levels.

Effect of biologic therapy on radiological progression in rheumatoid arthritis: what does it add to methotrexate?

Directory of Open Access Journals (Sweden)

Jones G

2012-07-01

Full Text Available Graeme Jones, Erica Darian-Smith, Michael Kwok, Tania WinzenbergMenzies Research Institute, University of Tasmania, Tasmania, AustraliaAbstract: There have been substantial advances in the treatment of rheumatoid arthritis in recent years. Traditional disease-modifying antirheumatic drugs (DMARDs have been shown to have small effects on the progression of radiographic damage. This quantitative overview summarizes the evidence for biologic DMARDS and radiographic damage either alone or in combination with methotrexate. Two outcomes were used (standardized mean difference and odds of progression. A total of 21 trials were identified of which 18 had useable data. For biologic monotherapy, tocilizumab, adalimumab, and etanercept were significantly better than methotrexate, with tocilizumab ranking first in both outcomes while golimumab was ineffective in both outcomes. For a biologic in combination with methotrexate compared with methotrexate alone, most therapies studied (etanercept, adalimumab, infliximab, certolizumab, tocilizumab, and rituximab were effective at slowing X-ray progression using either outcome, with infliximab ranking first in both outcomes. The exceptions to this were golimumab (no effect on standardized mean difference and abatacept (no effect on odds of progression. This effect was additional to methotrexate; thus, the overall benefit is moderate to large in magnitude, which is clearly of major clinical significance for sufferers of rheumatoid arthritis and supports the use of biologic DMARDs in those with a poor disease prognosis.Keywords: rheumatoid, trials, meta-analysis, radiographs, biologic, disease-modifying antirheumatic drugs, DMARDs

Intraocular methotrexate in the treatment of uveitis and uveitic cystoid macular edema.

Science.gov (United States)

Taylor, Simon R J; Habot-Wilner, Zohar; Pacheco, Patricio; Lightman, Sue L

2009-04-01

A pilot study to evaluate the use of intravitreal methotrexate (MTX) for the treatment of uveitis and uveitic cystoid macular edema (CME). Prospective, consecutive, interventional case series. Fifteen eyes of 15 patients with a unilateral exacerbation of noninfectious intermediate, posterior uveitis, or panuveitis and/or CME such that visual acuity (VA) was 20/40 or worse, together with a history of increased intraocular pressure (IOP) in response to corticosteroid administration. Intravitreal injection of 400 microg in 0.1 ml MTX. The primary outcome measure was VA (using the Early Treatment Diabetic Retinopathy Study chart). Other outcome measures included ocular inflammation scores, time to relapse, levels of systemic corticosteroid and immunosuppressive therapy, and ocular coherence tomography. Potential complications of intravitreal MTX injection, including cataract progression, vitreous hemorrhage, retinal detachment, and corneal epitheliopathy, were assessed. VA improved at all time points and was statistically significant at the 3- and 6-month follow-up examinations. The mean visual improvement was 4 lines at 3 months and 4.5 lines at 6 months, with no statistical difference between the best VA obtained after MTX injection and after previous corticosteroid treatment, including intravitreal triamcinolone acetate injection. Five patients relapsed after a median of 4 months; a similar improvement was seen after re-injection. Ocular inflammation scores improved at all time points, and systemic immunosuppressive medication was reduced in 3 of 7 patients taking this at the start of the trial. In patients with uveitis and uveitic CME, intravitreal MTX can improve VA and reduce CME and, in some patients, allows the reduction of immunosuppressive therapy. Relapse occurs at a median of 4 months in some patients, but reinjection has similar efficacy.

Interaction of methotrexate with trypsin analyzed by spectroscopic and molecular modeling methods

Science.gov (United States)

Wang, Yanqing; Zhang, Hongmei; Cao, Jian; Zhou, Qiuhua

2013-11-01

Trypsin is one of important digestive enzymes that have intimate correlation with human health and illness. In this work, the interaction of trypsin with methotrexate was investigated by spectroscopic and molecular modeling methods. The results revealed that methotrexate could interact with trypsin with about one binding site. Methotrexate molecule could enter into the primary substrate-binding pocket, resulting in inhibition of trypsin activity. Furthermore, the thermodynamic analysis implied that electrostatic force, hydrogen bonding, van der Waals and hydrophobic interactions were the main interactions for stabilizing the trypsin-methotrexate system, which agreed well with the results from the molecular modeling study.

Role of Caveolin 1, E-Cadherin, Enolase 2 and PKCalpha on resistance to methotrexate in human HT29 colon cancer cells

DEFF Research Database (Denmark)

Selga, Elisabet; Morales Torres, Christina; Noé, Véronique

2008-01-01

, a list of 3-fold differentially expressed genes with a p-value multiple testing correction (Benjamini and Hochberg false discovery rate) was generated. RT-Real-time PCR was used to validate the expression levels of selected genes and copy-number was determined by qPCR. Functional......ABSTRACT: BACKGROUND: Methotrexate is one of the earliest cytotoxic drugs used in cancer therapy, and despite the isolation of multiple other folate antagonists, methotrexate maintains its significant role as a treatment for different types of cancer and other disorders. The usefulness of treatment...

Efficacy of tofacitinib monotherapy in methotrexate-naive patients with early or established rheumatoid arthritis

NARCIS (Netherlands)

Fleischmann, Roy M.; Huizinga, Tom W. J.; Kavanaugh, Arthur F.; Wilkinson, Bethanie; Kwok, Kenneth; DeMasi, Ryan; van Vollenhoven, Ronald F.

2016-01-01

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Tofacitinib monotherapy was previously shown to inhibit structural damage, reduce clinical signs and symptoms of RA, and improve physical functioning over 24 months in methotrexate (MTX)-naive adult

Methotrexate is an effective treatment for chronic uveitis associated with juvenile idiopathic arthritis.

Science.gov (United States)

Foeldvari, Ivan; Wierk, Angela

2005-02-01

To assess the effectiveness of methotrexate (MTX) in the treatment of juvenile idiopathic arthritis (JIA) associated uveitis, which is still one of the most common causes of visual impairment. A retrospective chart review of patients with the diagnosis of uveitis associated with JIA between July 1, 2002, and December 31, 2002. Four hundred sixty-seven patients with JIA were followed. Thirty-eight had uveitis: 31 associated with oligoarticular JIA and 7 with psoriatic JIA. Twenty-five of the 38 patients received MTX; in 23 patients uveitis was the indication for MTX therapy. In the MTX treated group 46/50 eyes had uveitis, the mean (range) age at onset of uveitis was 7.82 years (1.8-15.8), and the mean age at onset of arthritis was 7.25 years (1.25-15.7). MTX treatment was started an average of 11.4 months (0-72) after the onset of uveitis. The mean MTX dose was 15.6 mg/m2. Remission occurred after 4.25 months (1-12). Mean duration of remission was 10.3 months (3-27). The total duration of MTX therapy was 661 months and patients were in remission for 417/661 months. In 6 patients MTX was discontinued after 12 months of remission. Four patients were still in remission after 7.5 months (1-14). MTX seems to be an effective therapy for JIA associated uveitis.

[Androgens and prolonged complete remissions in acute non lymphoblastic leukemias. Results of a systematic treatment with stanozolol associated with chemotherapy (author's transl)].

Science.gov (United States)

Sotto, J J; Hollard, D; Schaerer, R; Bensa, J C; Seigneurin, D

1975-01-01

An androgen (stanozolol: 0,15 mg/kg/d) was systematically associated to the treatment of acute non lymphoblastic leukemias, since the beginning of induction therapy (vincristin, daunorubicin, prednisone) and throughout the maintenance period (6-mercaptopurine and methotrexate). Thirty-six patients less than 60 years old (median age: 44 years) presenting with acute non-lymphoblastic leukemia were entered to the study. Sixteen achieved complete remission (C.R.), i.e. 44% of the whole and 53% of treated patients. Out of 16 patients with complete remission, 4 relapsed during the observation period which lasted 4-1/2 years. The stability of the hematologic equilibrium in patients in C.R. is the main finding of the present study. The actuarial curve of the duration of the first complete remission reaches a "plateau"; after the 8th month only one relapse was observed in 9 patients. The rate of C.R. at 2 years is 76 +/- 23%. As compared to the results from other schedules of treatment, this rate appears significantly better, specially in the case of immunotherapy (p less than 0,001). A prospective randomized study is now suggested as to confirm this result; its therapeutic and theoretical basis and perspectives are discussed.

Adverse effects of methotrexate in three psoriatic arthritis patients.

Science.gov (United States)

Maejima, Hideki; Watarai, Akira; Nakano, Toshiaki; Katayama, Chieko; Nishiyama, Hiromi; Katsuoka, Kensei

2014-04-01

Methotrexate, a folic acid analogue with anti-proliferative and anti-inflammatory effects, is commonly used to treat patients with severe destructive psoriatic arthritis and has considerable efficacy. Combined anti-tumor necrosis factor and MTX therapy result in less treatment discontinuation due to adverse events. Despite its efficacy, MTX may result in adverse effects including hepatic, pulmonary, and renal toxicity as well as lymphoproliferative disorders and predisposition to infection. We herein report rare adverse effects of MTX treatment, specifically asymptomatic pulmonary tuberculosis, renal cell carcinoma, and lateral uveitis, in three psoriatic arthritis patients treated with MTX. MTX is an important drug for the treatment for psoriatic arthritis patient, but an awareness of the possible adverse effects is needed.

Sequential Proximal Tibial Stress Fractures associated with Prolonged usage of Methotrexate and Corticosteroids: A Case Report

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Tan TJL

2015-11-01

Full Text Available Stress fractures of the proximal tibia metaphysis are rare in the elderly. We present a case of a 65-year old male who developed sequential proximal tibia stress fractures associated with prolonged usage of methotrexate and prednisolone within a span of 18 months. Magnetic Resonance Imaging revealed an incomplete stress fracture involving the medial proximal tibial region. The patient was treated with stemmed total knee arthroplasty (TKA bilaterally. Stress fractures should be considered in patients with atypical knee pain who have a history of methotrexate and prednisolone usage. TKA is an effective treatment in stress fractures of the proximal tibia.

Enhancement of the white matter following prophylactic therapy of the central nervous system for leukemia: radiation effects and methotrexate leukoencephalopathy

International Nuclear Information System (INIS)

Shalen, P.R.; Ostrow, P.T.; Glass, P.J.

1981-01-01

The authors report a case of fatal necrotizing leukoencephalopathy following prophylactic therapy of the central nervous system for acute lymphoblastic leukemia. The clinical, CT, and neuropathological findings are described. The CT scan demonstrated symmetrical white-matter enhancement. Histological analysis was consistent with the effects of irradiation and methotrexate. The differential diagnosis of the clinical and CT findings is discussed. Brain biopsy is the diagnostic procedure of choice

The complex treatment of acute pancreatitis using miniinvasive surgical treatment

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G. I. Ohrimenko

2015-06-01

Full Text Available Nowadays methods used in acute pancreatitis diagnostic do not allow to find the most optimal indications, terms of surgical drainage approaches in surgical treatment of acute pancreatitis. Aim. In order to develop optimal diagnostic and treatment algorithm 316 patients took part in the study. Methods and results. Surgery outcomes were assessed by the next methods: ultrasound, computed tomography. We determined that destructive changes in pancreas in group of sterile pancreatic necrosis were limited. In cases of infected pancreatic necrosis the damage was spread and the disease course was septic. That’s why the operative treatment in cases of sterile pancreatitis has to be used with strict indications such as fermentative peritonitis, acute liquid formations, acute pseudocysts. Conclusion. In such cases miniinvasive surgery is mainly used while in the cases of infected pancreatic necrosis we ought to choose open surgery treatment.

Methotrexate transport mechanisms: the basis for targeted drug delivery and ß-folate-receptor-specific treatment.

Science.gov (United States)

Fiehn, C

2010-01-01

Methotrexate (MTX) plays a pivotal role in the treatment of rheumatoid arthritis (RA). The transport mechanisms with which MTX reaches is target after application are an important part of MTX pharmacology and its concentration in target tissue such as RA synovial membrane might strongly influence the effectiveness of the drug. Physiological plasma protein binding of MTX to albumin is important for the distribution of MTX in the body and relative high concentrations of the drug are found in the liver. However, targeted drug delivery into inflamed joints and increased anti-arthritic efficiency can be obtained by covalent coupling of MTX ex-vivo to human serum albumin (MTX-HSA) or in-vivo to endogenous albumin mediated through the MTX-pro-drug AWO54. High expression of the folate receptor β (FR-β) on synovial macrophages of RA patients and its capacity to mediate binding and uptake of MTX has been demonstrated. To further improve drug treatment of RA, FR-β specific drugs have been developed and were characterised for their therapeutic potency in synovial inflammation. Therefore, different approaches to improve folate inhibitory and FR-β specific therapy of RA beyond MTX are in development and will be described.

Preparation and characterization of PLGA-β-CD polymeric nanoparticles containing methotrexate and evaluation of their effects on T47D cell line.

Science.gov (United States)

Gorjikhah, Fatemeh; Azizi Jalalian, Farid; Salehi, Roya; Panahi, Yunes; Hasanzadeh, Arash; Alizadeh, Effat; Akbarzadeh, Abolfazl; Davaran, Soodabeh

2017-05-01

Among all cancers that affect women, breast cancer has most mortality rate. It is essential to attain more safe and efficient anticancer drugs. Recent advances in medical nanotechnology and biotechnology have caused in novel improvements in breast and other cancer drug delivery. Methotrexate is an anticancer drug that prevents the dihydrofolate reductase enzyme, which inhibits in the formation of DNA, RNA and proteins which have poor water-solubility. For enhancing the solubility and stability of drugs in delivery systems, we used methotrexate-loaded PLGA- beta-cyclodextrin nanoparticles. The PLGA- beta-cyclodextrin nanoparticles were synthesized by a double emulsion method and characterized with FT-IR and SEM. T47D breast cancer cell lines were treated with equal concentrations of methotrexate-loaded PLGA- beta-cyclodextrin nanoparticles and free methotrexate. MTT assay confirmed that methotrexate-loaded PLGA- beta-cyclodextrin nanoparticles enhanced cytotoxicity and drug delivery in T47D breast cancer cells. These results indicate that encapsulated drugs could be effective in controlled drug release for a sustained period would serve the purpose for long-term treatment of many diseases such as breast cancer.

[Biofeedback treatment for acute whiplash patients].

Science.gov (United States)

Gálvez-Hernández, Carmen Lizette; Rodríguez-Ortiz, María Dolores; Del Río-Portilla, Yolanda

2016-01-01

The aim of this study is to evaluate the physiological and psychological effect after an electromyographic biofeedback treatment in combination with progressive muscular relaxation training in patients with acute whiplash. Twelve patients with acute whiplash volunteered to participate in a quasi-experimental design and a control group. Two months maximum after car accident, severity levels II and I. previous history of persistent pain or serious previous injury. The groups were randomly divided in two (treatment and waiting list groups). We used electromyographic measures of the trapezius muscles with psychometric tests: Beck Anxiety and Depression Inventory; Oswestry Pain Disability Questionnaire; Visual Analog Scale of Pain; TAMPA Scale for Kinesiophobia. The treatment consisted in electromyographic biofeedback after progressive muscular relaxation training. There were significant intra-group differences before and after treatment in muscular symmetry and subjective pain perception in the treatment group. We achieved a significant change (clinical and statistical) in subjective pain perception and muscular symmetry. This study highlights the importance of multidisciplinary work in acute pain patients and the effectiveness of clinical psychophysiological strategies with acute whiplash patients.

Comparison of intelligence quotient in children surviving leukemia who received different prophylactic central nervous system treatments

OpenAIRE

Nahid, Reisi; Leila, Khalilian

2012-01-01

Background: Neurocognitive deficits and decrease in intelligence quotient (IQ) is one of the complication of prophylactic central nervous system (CNS) treatment in acute lymphoblastic leukemia (ALL) patients. In this study, we compare the IQ in survivors of ALL that were treated with different prophylactic CNS treatments. Materials and Methods : We compared 43 long-term survivors of ALL: 21 survivors with intrathecal methotrexate (IT MTX) as CNS prophylaxis, 22 with IT MTX+1800-2400 rads c...

A randomised comparative study of the short term clinical and biological effects of intravenous pulse methylprednisolone and infliximab in patients with active rheumatoid arthritis despite methotrexate treatment

OpenAIRE

Durez, P; Nzeusseu, T; Lauwerys, B; Manicourt, D; Verschueren, P; Westhovens, R; Devogelaer, J; Houssiau, F

2004-01-01

OBJECTIVES: To compare the short term clinical and biological effects of intravenous (i.v.) pulse methylprednisolone (MP) and infliximab (IFX) in patients with severe active rheumatoid arthritis (RA) despite methotrexate (MTX) treatment. METHODS: Patients with active RA despite MTX treatment were randomly allocated to receive a single i.v. infusion of MP (1 g) or three i.v. infusions of IFX (3 mg/kg) on weeks 0, 2, and 6. Patients were "blindly" evaluated for disease activity measures. Qualit...

Folate overproduction in Lactobacillus plantarum WCFS1 causes methotrexate resistance

NARCIS (Netherlands)

Wegkamp, H.B.A.; Vos, de W.M.; Smid, E.J.

2009-01-01

Folate overproduction can serve as a mode of resistance against the folate antagonist methotrexate in Lactobacillus plantarum WCFS1. When compared with a wild-type control strain, an engineered high folate-producing strain was found to be insensitive to methotrexate. The growth rate and the viable

The impact of therapy for childhood acute lymphoblastic leukaemia on intelligence quotients; results of the risk-stratified randomized central nervous system treatment trial MRC UKALL XI

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Vargha-Khadem Faraneh

2011-10-01

Full Text Available Abstract Background The MRC UKALLXI trial tested the efficacy of different central nervous system (CNS directed therapies in childhood acute lymphoblastic leukaemia (ALL. To evaluate morbidity 555/1826 randomised children underwent prospective psychological evaluations. Full Scale, verbal and performance IQs were measured at 5 months, 3 years and 5 years. Scores were compared in; (1 all patients (n = 555 versus related controls (n = 311, (2 low-risk children (presenting white cell count (WCC 9/l randomised to intrathecal methotrexate (n = 197 versus intrathecal and high-dose intravenous methotrexate (HDM (n = 202, and (3 high-risk children (WCC ≥ 50 × 109/l, age ≥ 2 years randomised to HDM (n = 79 versus cranial irradiation (n = 77. Results There were no significant differences in IQ scores between the treatment arms in either low- or high-risk groups. Despite similar scores at baseline, results at 3 and 5 years showed a significant reduction of between 3.6 and 7.3 points in all three IQ scores in all patient groups compared to controls (P Conclusion Children with ALL are at risk of CNS morbidity, regardless of the mode of CNS-directed therapy. Further work needs to identify individuals at high-risk of adverse CNS outcomes. Trial registration ISRCTN: ISRCTN16757172

Affinity labeling of the folate-methotrexate transporter from Leishmania donovani

International Nuclear Information System (INIS)

Beck, J.T.; Ullman, B.

1989-01-01

An affinity labeling technique has been developed to identify the folate-methotrexate transporter of Leishmania donovani promastigotes using activated derivatives of the ligands. These activated derivatives were synthesized by incubating folate and methotrexate with a 10-fold excess of 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (EDC) for 10 min at ambient temperature in dimethyl sulfoxide. When intact wild-type (DI700) Leishmania donovani or preparations of their membranes were incubated with a 0.4 μM concentration of either activated [ 3 H]folate or activated [ 3 H]methotrexate, the radiolabeled ligands were covalently incorporated into a polypeptide with a molecular weight of approximately 46,000, as demonstrated by SDS-polyacrylamide gel electrophoresis. No affinity labeling of a 46,000-dalton protein was observed when equimolar concentrations of activated radiolabeled ligands were incubated with intact cells or membranes prepared from a methotrexate-resistant mutant clone of Leishmania donovani, MTXA5, that is genetically defective in folate-methotrexate transport capability. Time course studies indicated that maximal labeling of the 46,000-dalton protein occurred within 5-10 min of incubation of intact cells with activated ligand. These studies provide biochemical evidence that the folate-methotrexate transporter of Leishmania donovani can be identified in crude extracts by an affinity labeling technique and serve as a prerequisite to further analysis of the transport protein by providing a vehicle for subsequent purification of this membrane carrier. Moreover, these investigations suggest that the affinity labeling technique using EDC-activated ligands may be exploitable to analyze other cell surface binding proteins in Leishmania donovani, as well as in other organisms

Methotrexate-loaded biodegradable nanoparticles: preparation ...

Indian Academy of Sciences (India)

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In the present work, formulation and development of a novel methotrexate ... etc and also evaluated for its in vitro cytotoxic potential against U-343 MGa human neuronal glioblastoma ... 2.3a Particle size, polydispersity index and zeta poten-.

Etanercept in methotrexate-resistant JIA-related uveitis.

Science.gov (United States)

Saeed, Muhammad Usman; Raza, Syed Hamid; Goyal, Sudeshna; Cleary, Gavin; Newman, William David; Chandna, Arvind

2014-01-01

We report our results with systemic Etanercept in patients with juvenile idiopathic arthritis in a joint ophthalmology-rheumatology clinic at a tertiary hospital. Patients with JIA on Etanercept were identified from a dedicated uveitis database. A retrospective review of electronic and paper-based patient records was performed. Nine patients with JIA and current or previous treatment with Etanercept were identified, including six females and three males. Five patients with previous or current uveitis were noted. A further four were under observation for uveitis and required Etanercept for their joint disease. All nine patients had previously been taking Methotrexate, which had a suboptimal response in controlling arthritis or uveitis. Six out of nine patients did not show any uveitis activity at their last follow-up. Eyes of three patients still show signs of active inflammation in the anterior chamber (two on Etanercept and one off Etanercept). Severely impaired visual acuity (PL) was recorded in both eyes of one patient with long-standing persistent uveitis. Moderate visual loss in one eye of one patient was seen. The remaining seven patients did not show any significant loss of vision. Intraocular inflammation was not induced in any patient started on Etanercept. Etanercept may be useful in controlling JIA-related uveitis or arthritis in a pediatric patient when Methotrexate has had a suboptimal response in controlling the inflammatory activity.

Rationale for a pediatric-inspired approach in the adolescent and young adult population with acute lymphoblastic leukemia, with a focus on asparaginase treatment

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Carmelo Rizzari

2014-09-01

Full Text Available In the last two decades great improvements have been made in the treatment of childhood acute lymphoblastic leukemia, with 5-year overall survival rates currently approaching almost 90%. In comparison, results reported in adolescents and young adults (AYAs are relatively poor. In adults, results have improved, but are still lagging behind those obtained in children. Possible reasons for this different pattern of results include an increased incidence of unfavorable and a decreased incidence of favorable cytogenetic abnormalities in AYAs compared with children. Furthermore, in AYAs less intensive treatments (especially lower cumulative doses of drugs such as asparaginase, corticosteroids and methotrexate and longer gaps between courses of chemotherapy are planned compared to those in children. However, although favorable results obtained in AYAs receiving pediatric protocols have been consistently reported in several international collaborative trials, physicians must also be aware of the specific toxicity pattern associated with increased success in AYAs, since an excess of toxicity may compromise overall treatment schedule intensity. Cooperative efforts between pediatric and adult hematologists in designing specific protocols for AYAs are warranted.

Case Report: A child with acute lymphocytic leukaemia

African Journals Online (AJOL)

The patient was a child aged 5 years who had been diagnosed to have acute lymphocytic leukemia (ALL). Chemotherapy was given with wysolone, vincristine, daunomycin, l-asparaginase, and intrathecal methotrexate. In addition he was given fluconazole and co-trimoxazole to cover infections during the induction period ...

Study on the treatment of acute thallium poisoning.

Science.gov (United States)

Zhang, Hong-Tao; Qiao, Bao-Ping; Liu, Bao-Ping; Zhao, Xian-Guo

2014-05-01

Acute thallium poisoning rarely occurs but is a serious and even fatal medical condition. Currently, patients with acute thallium poisoning are usually treated with Prussian blue and blood purification therapy. However, there are few studies about these treatments for acute thallium poisoning. Nine patients with acute thallium poisoning from 1 family were treated successfully with Prussian blue and different types of blood purification therapies and analyzed. Prussian blue combined with sequential hemodialysis, hemoperfusion and/or continuous veno-venous hemofiltration were effective for the treatment of patients with acute thallium poisoning, even after delayed diagnosis. Blood purification therapies help in the clearance of thallium in those with acute thallium poisoning. Prussian blue treatment may do the benefit during this process.

Use of mycophenolate mofetil in patients with severe localized scleroderma resistant or intolerant to methotrexate

NARCIS (Netherlands)

Mertens, Jorre S.; Marsman, Diane; van de Kerkhof, Peter C M; Hoppenreijs, Esther P A H; Knaapen, Hanneke K A; Radstake, Timothy R D; de Jong, Elke M G J; Seyger, Marieke M B

2016-01-01

To assess the efficacy and safety of mycophenolate mofetil (MMF) in patients with localized scleroderma (LoS) resistant or intolerant to previous treatment with methotrexate (MTX). A case series of patients with LoS treated with MMF. Outcome was assessed through clinical examination. Adverse events

Superior outcome using cyclosporin A alone versus cyclosporin A plus methotrexate for post-transplant immunosuppression in children with acute leukemia undergoing sibling hematopoietic stem cell transplantation.

Science.gov (United States)

Weiss, Melissa; Steinbach, Daniel; Zintl, Felix; Beck, James; Gruhn, Bernd

2015-06-01

The outcome of cyclosporin A (CSA) alone (n = 19) as graft-versus-host disease (GVHD) prophylaxis was compared to that of CSA combined with methotrexate (MTX) (n = 43) in children with acute leukemia who underwent hematopoietic stem cell transplantation. All respective donors were HLA-identical siblings. All patients received CSA at a dose of 3 mg/kg/day starting on day -1. A CSA level of 80-130 ng/ml was aimed for. The 43 patients in the historical control were given an additional 10 mg/m(2) dosage of MTX on days 1, 3, 6, and 11. Patients who received CSA alone had a significantly reduced cumulative incidence of relapse (5 vs. 40 %; p = 0.002), a significantly increased 5-year event-free survival (84 vs. 35 %; p = 0.001), and a significantly increased 5-year overall survival (84 vs. 42 %; p = 0.004). The incidence of acute GVHD grade II-IV and chronic GVHD in patients in the CSA group was equivalent to the CSA+MTX group (26 vs. 19 %; p = 0.440, and 32 vs. 23 %; p = 0.428). In conclusion, post-transplant immunosuppression consisting of CSA alone is well tolerated and may contribute to a superior outcome.

Can the Methotrexate Therapy Prevent the Development of Uveitis in Patients with Juvenile Idiopathic Arthritis: Results of a Retrospective Study

OpenAIRE

M. M. Kostik; E. V. Gaydar; M. F. Dubko; V. V. Masalova; L. S. Snegireva; I. A. Chikova; E. A. Isupova; T. N. Nikitina; E. D. Serogodskaya; O. V. Kalashnikova; A. Ravelli; V. G. Chasnyk

2015-01-01

Background: Uveitis is one of the most common extra-articular manifestations of juvenile idiopathic arthritis (JIA). Currently, the possibility of reducing the risk of uveitis in children with JIA by using methotrexate has been studied.Objective: Our aim was to analyze the results of treatment of children with JIA by studying the relation between the use of methotrexate and the risk of uveitis.Methods: A retrospective uncontrolled study. The case histories of patients with JIA who were treate...

Brain Function in Young Patients Receiving Methotrexate for Acute Lymphoblastic Leukemia

Science.gov (United States)

2017-07-19

Childhood B Acute Lymphoblastic Leukemia; Childhood T Acute Lymphoblastic Leukemia; Cognitive Side Effects of Cancer Therapy; Long-Term Effects Secondary to Cancer Therapy in Children; Neurotoxicity Syndrome; Psychological Impact of Cancer; Untreated Childhood Acute Lymphoblastic Leukemia

Relapse rate of uveitis post-methotrexate treatment in juvenile idiopathic arthritis.

Science.gov (United States)

Kalinina Ayuso, Viera; van de Winkel, Evelyne Leonce; Rothova, Aniki; de Boer, Joke Helena

2011-02-01

To evaluate the efficacy of methotrexate (MTX) and the effect of its withdrawal on relapse rate of uveitis associated with juvenile idiopathic arthritis (JIA). Retrospective case series. Data of 22 pediatric JIA patients who were being treated with MTX for active uveitis were studied retrospectively. Relapse rate after the withdrawal of MTX was established. Anterior chamber (AC) inflammation, topical steroid use during the first year of MTX treatment, and associations of relapses after the withdrawal were evaluated statistically. Duration of MTX treatment and its withdrawal was determined individually in collaboration with a rheumatologist with an intention to continue the treatment for at least 1 year and to withdraw in case of inactivity of uveitis and arthritis. Inactivity of uveitis was defined as the presence of ≤0.5+ cells in the AC. Eighteen patients (18/22; 82%) showed improvement of their uveitis with a significant decrease in activity of AC inflammation after a minimal period of 3 months of MTX treatment. A topical steroid-sparing effect was observed when MTX was administered for a period of 3 to 9 months. MTX was discontinued because of inactive uveitis in 13 patients. In 9 patients (8/13; 69%) a relapse of uveitis was observed after a mean time of 7.5 months (± SD 7.3). Six patients (6/13; 46%) had a relapse within the first year after the withdrawal. Relapse-free survival after withdrawal of MTX was significantly longer in patients who had been treated with MTX for more than 3 years (P = .009), children who were older than 8 years at the moment of withdrawal (P = .003), and patients who had an inactivity of uveitis of longer than 2 years before withdrawal of MTX (P = .033). Longer inactivity under MTX therapy was independently protective for relapses after the withdrawal (hazard ratio = 0.07; 95% confidence interval 0.01-0.86; P = .038), which means that 1-year increase of duration of inactive uveitis before the withdrawal of MTX results in a

Treatment and prevention of acute radiation dermatitis

International Nuclear Information System (INIS)

Benomar, S.; Hassam, B.; Boutayeb, S.; Errihani, H.; Lalya, I.; El Gueddari, B.K.

2010-01-01

Acute radiation dermatitis is a common side-effect of radiotherapy which often necessitates interruption of the therapy. Currently, there is no general consensus about its prevention or about the treatment of choice. The goal of this work was to focus on optimal methods to prevent and manage acute skin reactions related to radiation therapy and to determine if there are specific topical or oral agents for the prevention of this acute skin reaction. The prevention and the early treatment are the two focus points of the management of the acute radiation dermatitis. (authors)

Circulating levels of osteoprotegerin and sRANKL and the effect of methotrexate in patients with rheumatoid arthritis

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Aadhaar Dhooria

2018-01-01

Conclusions: OPG levels are higher in RA patients and normalize in response to treatment with methotrexate. The initial higher levels of OPG may represent a compensatory mechanism to osteoclast activation; they normalize on reduction of disease activity.

Effects of growth hormone plus a hyperproteic diet on methotrexate-induced injury in rat intestines.

Science.gov (United States)

Ortega, M; Gomez-de-Segura, I A; Vázquez, I; López, J M; de Guevara, C L; De-Miguel, E

2001-01-01

The aim of this study was to determine whether growth hormone treatment reduces injury to the intestinal mucosa induced by methotrexate (MTX). Wistar rats with intestinal injury induced by methotrexate were treated with daily growth hormone, beginning 3 days before MTX treatment until 3 or 4 days after MTX administration. The rats were killed at 3 or 7 days post-MTX administration. The rats were fed with either a normoproteic diet or a hyperproteic diet. Body weight, mortality, bacterial translocation, intestinal morphometry, proliferation and apoptosis and blood somatostatin and IGF-1 were determined. Combined administration of growth hormone and a hyperproteic diet reduces MTX-induced mortality. This effect was accompanied by increased cell proliferation and decreased apoptosis within the crypt. Morphometric data showed complete recovery of the mucosa by day 7 post-MTX administration. These results indicate a synergistic protective action of growth hormone combined with a hyperproteic diet to MTX-induced injury.

Urgencias hematológicas. III. Toxicidad por metotrexato Hematological emergencies. III. Methotrexate toxicity

Directory of Open Access Journals (Sweden)

Juan Carlos Jaime-Fagundo

2012-09-01

Full Text Available El metotrexato es un antimetabolito que inhibe competitivamente la enzima dihidrofolato reductasa y posee actividad antiproliferativa e inmunosupresora, por lo que se emplea en el tratamiento de diferentes hemopatías malignas. Los principales efectos adversos son mielosupresión, insuficiencia renal, mucositis y alteraciones neurológicas. Es de gran importancia que el manejo de la intoxicación por esta droga sea rápido y adecuado, ya que una acción a tiempo es capaz no solo revertir de el daño, sino de salvar la vida del paciente. Se hace una revisión de la conducta frente a la toxicidad aguda por este medicamento.Methotrexate is an antimetabolite which competitively inhibits the dihydrofolate reductase enzyme and has anti-proliferative and immunosuppressive activity and therefore it is used in the treatment of various hematological malignancies. The main adverse effects are myelosuppression, renal insufficiency, mucositis and neurological disorders. The adequate management of intoxication by this drug is very important since fast and appropriate actions can reverse the damage and save the patient's life. A review of the behaviour against acute toxicity by this drug is reported.

Actuarial risk of isolated CNS involvement in Ewing's sarcoma following prophylactic cranial irradiation and intrathecal methotrexate

International Nuclear Information System (INIS)

Trigg, M.E.; Makuch, R.; Glaubiger, D.

1985-01-01

Records of 154 patients with Ewing's sarcoma treated at the National Cancer Institute were reviewed to assess the incidence and risk of developing isolated central nervous system (CNS) Ewing's sarcoma. Sixty-two of the 154 patients had received CNS irradiation and intrathecal (i.t.) methotrexate as part of their initial therapy to prevent the occurrence of isolated CNS Ewing's sarcoma. The risk of developing isolate CNS Ewing's sarcoma was greatest within the first two years after diagnosis and was approximately 10%. The overall risk of CNS recurrence in the group of patients receiving DNS treatment was similar to the group receiving no therapy directed to the CNS. The occurrence of isolated CNS involvement was not prevented by the use of CNS irradiation and i.t. methotrexate. Because of a lack of efficacy to the CNS irradiation regimen, current treatment regimens do not include therapy directed to CNS

Acute aortic syndromes: definition, prognosis and treatment options.

Science.gov (United States)

Carpenter, S W; Kodolitsch, Y V; Debus, E S; Wipper, S; Tsilimparis, N; Larena-Avellaneda, A; Diener, H; Kölbel, T

2014-04-01

Acute aortic syndromes (AAS) are life-threatening vascular conditions of the thoracic aorta presenting with acute pain as the leading symptom in most cases. The incidence is approximately 3-5/100,000 in western countries with increase during the past decades. Clinical suspicion for AAS requires immediate confirmation with advanced imaging modalities. Initial management of AAS addresses avoidance of progression by immediate medical therapy to reduce aortic shear stress. Proximal symptomatic lesions with involvement of the ascending aorta are surgically treated in the acute setting, whereas acute uncomplicated distal dissection should be treated by medical therapy in the acute period, followed by surveillance and repeated imaging studies. Acute complicated distal dissection requires urgent invasive treatment and thoracic endovascular aortic repair has become the treatment modality of choice because of favorable outcomes compared to open surgical repair. Intramural hematoma, penetrating aortic ulcers, and traumatic aortic injuries of the descending aorta harbor specific challenges compared to aortic dissection and treatment strategies are not as uniformly defined as in aortic dissection. Moreover these lesions have a different prognosis. Once the acute period of aortic syndrome has been survived, a lifelong medical treatment and close surveillance with repeated imaging studies is essential to detect impending complications which might need invasive treatment within the short-, mid- or long-term.

What is new HLA-B27 acute anterior uveitis?

Science.gov (United States)

Wakefield, Denis; Chang, John H; Amjadi, Shahriar; Maconochie, Zoe; Abu El-Asrar, Ahmed; McCluskey, Peter

2011-04-01

Acute anterior uveitis (AAU) is the most common form of uveitis, accounting for approximately 90% of all cases. Half of all cases of AAU are HLA-B27 positive. The disease is typically acute in onset, unilateral, nongranulomatous inflammation involving the iris and ciliary body, with a tendency to recurrent attacks. Approximately 50% of all patients with HLA-B27 AAU develop an associated seronegative arthritis (SNA), while approximately 25% of the patients initially diagnosed with HLA-B27 SNA develop AAU. Environmental factors play a critical role in the pathogenesis of AAU; in particular, bacterial triggers have been strongly implicated in the development of this disease. Topical corticosteroids and cycloplegic agents remain the cornerstones of treatment for AAU. Salazopirine and methotrexate are effective in decreasing recurrent attacks. Biological agents such as anti-TNF and anti-CD20 therapy may be effective in refractory severe AU but are rarely required.

Evaluation of the concomitant use of methotrexate and curcumin on Freund's complete adjuvant-induced arthritis and hematological indices in rats.

Science.gov (United States)

Banji, David; Pinnapureddy, Jyothi; Banji, Otilia J F; Kumar, A Ranjith; Reddy, K Narsi

2011-09-01

To evaluate the concomitant administration of methotrexate and curcumin for antiarthiritic activity in rats. Arthritis was induced in rats following a single subplantar injection of Freund's complete adjuvant (0.1 ml). Rats were divided into six groups of six animals each. Group I and II were control injected with saline and Freund's complete adjuvant (0.1 ml), respectively. Group III arthritic rats were treated with curcumin (100 mg/kg, i.p.) on alternate days. Group IV received methotrexate (MTX) (2 mg/kg, i.p.) once in a week. Group-V and VI were treated with MTX (1 mg/kg, i.p.) once in a week and after 30 min received curcumin (30 mg/kg and 100 mg/kg, thrice a week, i.p.) from 10(th) to 45(th) days, respectively. Body weight and the paw volume was measured on 9(th), 16(th), 23(rd), 30(th), 37(th), and 45(th) days. Determination of complete blood cell counts, hemoglobin concentration, hematocrit, mean corpuscular volume, and mean corpuscular hemoglobin concentration was determined on the 46(th) day. An improvement in body weight and a significant (P arthritis was observed with the combination treatment as compared to the positive control. A significant improvement in the hematological profile was also observed in rats treated with curcumin and methotrexate. The study showed a significant anti-arthritic action and protection from hematological toxicity with the combination treatment of methotrexate and curcumin.

Time to treatment as an important factor for the response to methotrexate in juvenile idiopathic arthritis.

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Albers, H M; Wessels, J A M; van der Straaten, R J H M; Brinkman, D M C; Suijlekom-Smit, L W A; Kamphuis, S S M; Girschick, H J; Wouters, C; Schilham, M W; le Cessie, S; Huizinga, T W J; Ten Cate, R; Guchelaar, H J

2009-01-15

Methotrexate (MTX) is the most commonly used disease-modifying antirheumatic drug in juvenile idiopathic arthritis (JIA). Currently, individual response to MTX cannot be reliably predicted. Identification of clinical and genetic factors that influence the response to MTX could be helpful in realizing the optimal treatment for individual patients. A cohort of 128 JIA patients treated with MTX were studied retrospectively. Eleven clinical parameters and genotypes of 6 single nucleotide polymorphisms in 5 genes related to the mechanism of action of MTX were compared between MTX responders and nonresponders using a multivariate regression analysis. The time from diagnosis to start of MTX treatment, physician's global assessment at baseline, and the starting dose were significantly associated with the response to MTX at 6 months after initiation. Patients with a shorter time from diagnosis to start of MTX and a higher disease activity according to the physician but with a lower MTX dose showed an increased response. The effect of the starting dose on MTX response seemed to be mainly due to the influence of the systemic JIA subtype. The time from diagnosis to start of MTX treatment and physician's global assessment at baseline were highly correlated. Therefore, the precise effect size of each independent variable could not be determined. In children with JIA, the time from diagnosis to start of MTX appears to be an important factor for MTX response. Our results suggest that an earlier start of MTX treatment will lead to an increased response.

In-Patient Treatment of Severe Acute Malnutrition

DEFF Research Database (Denmark)

Rytter, Maren Johanne Heilskov

Severe acute malnutrition is a serious health problem among children in low-income countries. Particularly malnourished children requiring in-hospital treatment are at high risk of dying. This dissertation investigates possible reasons for this high mortality, by following a group of 120 children...... during their in-hospital treatment of severe acute malnutrition at Mwanamugimu Nutrition Unit in Kampala, Uganda. We assessed how malnutrition affected the children’s immune system, by measuring the size of their thymus gland with ultrasound. We examined characteristics of children with the serious form...... of malnutrition, Kwashiorkor, where the children develop oedema. Finally, we explored symptoms, findings or treatments given that were associated with a higher risk of death in the children. Hopefully, these findings may contribute to improving the treatment offered to children with severe acute malnutrition....

CD5-Positive Primary Intraocular B-Cell Lymphoma Arising during Methotrexate and Tumor Necrosis Factor Inhibitor Treatment

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Kenji Nagata

2015-09-01

Full Text Available Purpose: To report a case of CD5+ primary intraocular B-cell lymphoma arising during methotrexate (MTX and tumor necrosis factor (TNF inhibitor treatment in a young patient with rheumatoid arthritis and uveitis. Case Presentation: A 39-year-old woman treated with MTX and a TNF inhibitor for rheumatoid arthritis and uveitis had steroid-resistant vitreous opacity. A vitreous sample was obtained by using diagnostic vitrectomy and was categorized as class V based on cytologic examination. Flow cytometric analysis of the vitreous sample revealed that abnormal cells were CD5+, CD10-, CD19+, CD20+ and immunoglobulin light-chain kappa+, suggesting the diagnosis of CD5+ primary intraocular B-cell lymphoma. Polymerase chain reaction (PCR detected immunoglobulin heavy-chain gene rearrangement. Epstein-Barr virus (EBV DNA was detected in the vitreous sample by using PCR, and immunohistochemistry revealed EBV latent membrane protein-1 expression in the abnormal cells infiltrating the vitreous. Optic nerve invasion was observed on magnetic resonance imaging. Conclusion: Primary intraocular lymphoma (PIOL may develop in patients receiving MTX and TNF inhibitor treatment. EBV infection may play an important role in the pathogenesis of PIOL arising during immunosuppressive therapy.

Methotrexate in ocular manifestations of Behcet's disease: a longitudinal study up to 15 years.

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Davatchi, Fereydoun; Shams, Hormoz; Shahram, Farhad; Nadji, Abdolhadi; Chams-Davatchi, Cheyda; Sadeghi Abdollahi, Bahar; Faezi, Tahereh; Akhlaghi, Massoomeh; Ashofteh, Farimah

2013-10-01

Ocular manifestations of Behcet's disease (BD) need aggressive treatment to prevent severe loss of vision or blindness. Cytotoxic drugs are the main therapeutic agents and the first line treatment. Methotrexate is the least toxic, used mainly for posterior uveitis. We present here the outcome of eye lesions with methotrexate and prednisolone, in a longitudinal study of up to 15 years, on 682 patients (5447 eye-years of follow-up). Methotrexate was started at 7.5-15 mg/week. Prednisolone was added at 0.5 mg/kg/daily, then adjusted as needed. (i) fulfilling the International Criteria for Behcet's Disease; and (ii) having active posterior uveitis (PU). Visual acuity (VA) was calculated on a scale of 10. Activity indexes were calculated for PU and retinal vasculitis (RV) for each eye. Total Inflammatory Activity Index (TIAI) demonstrating the inflammatory index of both eyes of the patient, and Total Adjusted Disease Activity Index (TADAI) showing both TIAI + VA were also calculated. Overall results: the mean VA improvement was 0.4 (P < 001), PU 1.2 (P < 0.001) and RV 0.6 (P < 0.001). VA improved in 46.5%, PU in 75.4%, and RV in 53.7% of eyes. TIAI improved in 74% of patients and TADAI in 69.4%. VA was aggravated in 37.2%, PU in 11.1%, and RV in 30.3% of eyes. TIAI was aggravated in 17.4% and TADAI in 21.6% of the patients. The remaining kept their baseline values. All parameters improved, PU better than RV. Improvement of VA was the least, mainly due to secondary cataracts. © 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Methotrexate information booklet study 2008.

LENUS (Irish Health Repository)

Mohammad, A

2012-02-01

INTRODUCTION: I n order to assess the value of using the methotrexate information booklet, we conducted a single blind prospective controlled trial of the patients attending two rheumatology services. METHODS: The active-arm (n=40) used the MTX information booklet for the patients\\' education and the control-arm (n=38) did not. Patients\\' interviews were conducted over a 6-month period using an MTX-questionnaire. RESULTS: The entire active-arm patients (100%) were taking folic-acid and 32 (80%) knew the reason why they were taking folic-acid vs. [30 (79%) and 10 (26%) in the control-arm]. In the active-arm 35 (88%) knew the reason for their monthly blood tests vs. 18 (47%) in the control-arm. The entire active-arm was aware of the need for contraception use and MTX-side effects vs. 23 (60%) and 15 (40%) in the control-arm respectively. CONCLUSIONS: The use of the MTX information booklet in our cohort improved their understanding of the treatment.

Enzymatic assay for methotrexate in erythrocytes

DEFF Research Database (Denmark)

Schrøder, H; Heinsvig, E M

1985-01-01

Methotrexate (MTX) accumulates in erythrocytes in MTX-treated patients. We present a modified enzymatic assay measuring MTX concentrations between 10 and 60 nmol/l in erythrocytes, adapted for a centrifugal analyser (Cobas Bio). About 40 patient's samples could be analysed within 1 h. The detection...

[Weekly low-dose methotrexate in rheumatoid arthritis. Review of the literature].

Science.gov (United States)

Manganelli, P; Troise Rioda, W

1993-10-01

Methotrexate (MTX) is an antifolic drug that in recent years has been largely employed in the treatment of Rheumatoid Arthritis (RA). Both short and long term clinical trials have demonstrated its efficacy and good tolerability. It induces a significant improvement of all clinical variables and a decrease in the erythrocyte sedimentation rate and other acute phase reactants with a steroid sparing effect. The probability of continuing MTX therapy for up to 5 years is 46-55% whereas that of continuing gold, hydroxychloroquine, sulfasalazine or D-penicillamine therapy is less than 20%. MTX is a rapidly acting drug with a clinical response within 4 weeks and a plateau phase after 6 months of therapy. Discontinuation of long-term MTX therapy induces a flare-up of the disease so that patients receiving long-term MTX must continue the drug to maintain clinical benefits. In spite of its clinical efficacy, MTX does not seem to have a significant effect on disease progression as determined radiographically. In this respect, MTX appears to have some superiority when compared to azathioprine, but not when compared to gold salts. MTX has been employed in patients with RA unresponsive to other Disease-Modifying Antirheumatic Drugs (DMARDs), but according to some recent views on the therapeutic strategy of RA, it could be used in early RA as a first choice drug. Toxic effects are the main reason in limiting long-term MTX treatment. Hepatic toxicity is one of the more common side-effects of MTX, but the recognition of its "risk factors" such as alcohol abuse, may reduce it. Acute pneumonitis is one of the more severe complications of MTX therapy and may be life-threatening. In RA patients treated with MTX are also reported complications of immunosuppression, such as Pneumocystis carinii pneumonia whose clinical-radiological picture may be similar to that of acute pneumonitis. The mechanism of action of low-dose weekly MTX in RA is still unclear, but it might be more

Preliminary study for predicting better methotrexate efficacy in Japanese patients with rheumatoid arthritis

OpenAIRE

Hashiguchi, Masayuki; Tsuru, Tomomi; Miyawaki, Kumika; Suzaki, Midori; Hakamata, Jun; Shimizu, Mikiko; Irie, Shin; Mochizuki, Mayumi

2016-01-01

Background Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic inflammatory status, joint destruction, disability, and pain. Methotrexate (MTX) has been confirmed to reduce disease activity and delay or stabilize the development of bone erosions. However, major drawbacks are that patients show great interindividual variability in response to MTX and the unpredictable occurrence of side effects. A strategy for personalized MTX treatment to predict its efficacy a...

Pharmacogenetics predictive of response and toxicity in acute lymphoblastic leukemia therapy.

Science.gov (United States)

Mei, Lin; Ontiveros, Evelena P; Griffiths, Elizabeth A; Thompson, James E; Wang, Eunice S; Wetzler, Meir

2015-07-01

Acute lymphoblastic leukemia (ALL) is a relatively rare disease in adults accounting for no more than 20% of all cases of acute leukemia. By contrast with the pediatric population, in whom significant improvements in long term survival and even cure have been achieved over the last 30years, adult ALL remains a significant challenge. Overall survival in this group remains a relatively poor 20-40%. Modern research has focused on improved pharmacokinetics, novel pharmacogenetics and personalized principles to optimize the efficacy of the treatment while reducing toxicity. Here we review the pharmacogenetics of medications used in the management of patients with ALL, including l-asparaginase, glucocorticoids, 6-mercaptopurine, methotrexate, vincristine and tyrosine kinase inhibitors. Incorporating recent pharmacogenetic data, mainly from pediatric ALL, will provide novel perspective of predicting response and toxicity in both pediatric and adult ALL therapies. Copyright © 2015 Elsevier Ltd. All rights reserved.

Nodulose por Metotrexato Methotrexate Induced Nodulosis

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Fernanda Guidolin

2005-08-01

Full Text Available A nodulose por metotrexato (MTX é um dos efeitos colaterais pouco conhecidos do uso desse medicamento em doses baixas. Embora classicamente descrita em casos de artrite reumatóide, tem aparecido, também, em outras doenças reumáticas. Descreve-se aqui um caso de nodulose por MTX em uma paciente com artrite reumatóide soropositiva, que utilizava esse medicamento há um ano, com bom controle do processo articular. Segue-se uma breve revisão sobre o assunto.Methotrexate-induced nodulosis is a rare side effect of this drug when it is used in low doses. Although classically described in rheumatoid arthritis patients, it may also appear in other rheumatic disorders. We describe a seropositive rheumatoid arthritis patient who developed methotrexate-induced nodulosis after using this drug for a year, with good control of articular symptoms. This case presentation is followed by a brief revision on the subject.

Microbubbles coupled to methotrexate-loaded liposomes for ultrasound-mediated delivery of methotrexate across the blood–brain barrier

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Wang X

2014-10-01

Full Text Available Xiang Wang,1 Ping Liu,1 Weixiao Yang,1 Lu Li,1 Peijing Li,2 Zheng Liu,1 Zhongxiong Zhuo,1 Yunhua Gao1 1Department of Ultrasound, Xinqiao Hospital of the Third Military Medical University, Chongqing, 2Department of Ultrasound, General Hospital of the Jinan Military Area, Jinan, People’s Republic of China Abstract: Methotrexate (MTX is the single most effective agent for the treatment of primary central nervous system lymphoma. Currently, the delivery of MTX to the brain is achieved by high systemic doses, which cause severe long-term neurotoxicity, or intrathecal administration, which is highly invasive and may lead to infections or hemorrhagic complications. Acoustically active microbubbles have been developed as drug carriers for the noninvasive and brain-targeted delivery of therapeutics. However, their application is limited by their low drug-loading capacity. To overcome this limitation, we prepared microbubbles coupled to MTX-loaded liposomes using ZHIFUXIAN, a novel type of microbubbles with a superior safety profile and long circulation time. MTX-liposome-coupled microbubbles had a high drug-loading capacity of 8.91%±0.86%, and their size (2.64±0.93 µm in diameter was suitable for intravenous injection. When used with ultrasound, they showed more potent in vitro cytotoxicity against Walker-256 cancer cells than MTX alone or MTX-loaded liposomes. When Sprague-Dawley rats were exposed to sonication, administration of these MTX-liposome-coupled microbubbles via the tail vein led to targeted disruption of the blood–brain barrier without noticeable tissue or capillary damage. High-performance liquid chromatography analysis of the brain MTX concentration showed that MTX delivery to the brain followed the order of MTX-liposome-coupled microbubbles + ultrasound (25.3±2.4 µg/g > unmodified ZHIFUXIAN + MTX + ultrasound (18.6±2.2 µg/g > MTX alone (6.97±0.75 µg/g > MTX-liposome-coupled microbubbles (2.92±0.39 µg/g. Therefore

Efficacy of tofacitinib monotherapy in methotrexate-naive patients with early or established rheumatoid arthritis

OpenAIRE

Fleischmann, Roy M; Huizinga, Tom W J; Kavanaugh, Arthur F; Wilkinson, Bethanie; Kwok, Kenneth; DeMasi, Ryan; van Vollenhoven, Ronald F

2016-01-01

Introduction Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Tofacitinib monotherapy was previously shown to inhibit structural damage, reduce clinical signs and symptoms of RA, and improve physical functioning over 24?months in methotrexate (MTX)-naive adult patients with RA. In this post hoc analysis, we compared efficacy and safety of tofacitinib in patients with early (disease duration

High prevalence of methotrexate intolerance in juvenile idiopathic arthritis : development and validation of a methotrexate intolerance severity score

NARCIS (Netherlands)

Bulatović, Maja; Heijstek, Marloes W; Verkaaik, Marleen; van Dijkhuizen, E H Pieter; Armbrust, Wineke; Hoppenreijs, Esther P A; Kamphuis, Sylvia; Kuis, Wietse; Egberts, Toine C G; Sinnema, Gerben; Rademaker, Carin M A; Wulffraat, Nico M

OBJECTIVE: To design and validate a new questionnaire for identifying patients with methotrexate (MTX) intolerance, and to determine the prevalence of MTX intolerance in patients with juvenile idiopathic arthritis (JIA) using this questionnaire. METHODS: The MTX Intolerance Severity Score (MISS)

High prevalence of methotrexate intolerance in juvenile idiopathic arthritis: development and validation of a methotrexate intolerance severity score

NARCIS (Netherlands)

Bulatovic, M.; Heijstek, M.W.; Verkaaik, M.; Dijkhuizen, E.H. van; Armbrust, W.; Hoppenreijs, E.P.A.H.; Kamphuis, S.; Kuis, W.; Egberts, T.C.; Sinnema, G.; Rademaker, C.M.A.; Wulffraat, N.M.

2011-01-01

OBJECTIVE: To design and validate a new questionnaire for identifying patients with methotrexate (MTX) intolerance, and to determine the prevalence of MTX intolerance in patients with juvenile idiopathic arthritis (JIA) using this questionnaire. METHODS: The MTX Intolerance Severity Score (MISS)

The Influence of Methotrexate Treatment on Male Fertility and Pregnancy Outcome After Paternal Exposure.

Science.gov (United States)

Grosen, Anne; Kelsen, Jens; Hvas, Christian Lodberg; Bellaguarda, Emanuelle; Hanauer, Stephen B

2017-04-01

Inflammatory bowel disease incidence peaks during the reproductive years. Methotrexate (MTX) is frequently used for inflammatory bowel disease, but its use during pregnancy is contraindicated in women because of teratogenic effects. The aim of this review is to investigate the influence of MTX on male fertility and pregnancy outcomes after paternal MTX exposure. A systematic literature search was performed by applying 2 focus areas, "methotrexate" and "male fertility or pregnancy outcome." Terms and keywords were used both as MeSH terms and free-text searches. Pertinent articles were searched for additional relevant references. In animal studies, MTX induces aberrations in sperm DNA that have not been identified in humans. The effects of MTX on human sperm quality have only been described in case reports. A transient adverse effect on sperm quality with low-dose MTX has been reported, but several other cases have not found harmful effects of MTX. MTX has not been measured in human sperm ejaculates; yet, the risk of a direct toxic effect on the fetus through MTX-contaminated seminal plasma seems negligible. Until now, 284 pregnancies with paternal MTX exposure have been reported. The outcomes were 248 live births and a total of 13 malformations, with no overt indication of MTX embryopathy. This review reveals the lack of studies on the safety of MTX with regard to male reproduction. It is not clear whether MTX transiently influences male fertility and sperm DNA integrity, and more studies are needed. Comparative cohort studies found no increased risk of adverse pregnancy outcomes.

Real-World Treatment Patterns for Golimumab and Concomitant Medications in Japanese Rheumatoid Arthritis Patients.

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Okazaki, Masateru; Kobayashi, Hisanori; Ishii, Yutaka; Kanbori, Masayoshi; Yajima, Tsutomu

2018-06-01

The aim of this study was to investigate real-world treatment patterns for use of golimumab and concomitant medications in Japanese patients with rheumatoid arthritis. This study was a post hoc retrospective analysis from post-marketing surveillance data on 2350 Japanese patients with moderate/severe rheumatoid arthritis who received golimumab for 24 weeks. The study population was divided based on initiation treatment or dose adjustment patterns with golimumab, methotrexate, or oral glucocorticoids. Logistic regression analysis revealed that the baseline factors associated with administration of golimumab (100 mg) were higher body weight, failure of prior biological therapy (bio-failure), no previous methotrexate use, and respiratory disease, while previous methotrexate use and absence of renal impairment or respiratory disease were associated with concomitant methotrexate therapy, and previous glucocorticoid use was associated with concomitant glucocorticoid therapy. The following associations were identified with regard to dose adjustment during treatment: bio-failure, no previous methotrexate use, previous csDMARDs use, presence of respiratory disease, allergy history, and higher CRP for golimumab dose escalation; shorter disease duration, previous GC, and no previous methotrexate use for methotrexate dose escalation; no prior biological therapy and renal impairment for methotrexate dose reduction; no previous GC use for glucocorticoid dose escalation; and absence of Steinbrocker's stage II/III/IV, absence of Steinbrocker's class II, no bio-failure, and no previous csDMARDs use for glucocorticoid dose reduction. This study revealed that various baseline factors were associated with initiation of treatment and dose adjustment of golimumab, methotrexate, or oral glucocorticoids, reflecting both the treatment strategies of physicians for improving RA symptoms and/or reducing adverse events. Janssen Pharmaceutical K.K. and Mitsubishi Tanabe Pharma Corporation.

Delivery of Methotrexate and Characterization of Skin Treated by Fabricated PLGA Microneedles and Fractional Ablative Laser.

Science.gov (United States)

Nguyen, Hiep X; Banga, Ajay K

2018-02-21

This study investigated in vitro transdermal delivery of methotrexate through dermatomed porcine ear and cadaver human skin treated with poly (D,L-lactide-co-glycolide) acid microneedles or fractional ablative laser. PLGA microneedles were fabricated and characterized using scanning electron microscopy and mechanical assessment techniques. The integrity of treated skin was evaluated by rheometer, transepidermal water loss, and skin electrical resistance measurements. Successful skin microporation was demonstrated by dye binding, histology, pore uniformity, confocal laser microscopy, and DermaScan studies. In vitro permeation experiment was performed on Franz diffusion cells to determine drug delivery into and across the skin. Both physical treatments resulted in a considerable decrease in skin resistance and an increase in transepidermal water loss value. The laser-created microchannels were significantly larger than those formed by microneedles (p < 0.05). An effective force of 41.04 ± 18.33 N was required to achieve 100% penetration efficiency of the microneedles. For both porcine ear and human skin, laser ablation provided a significantly higher methotrexate permeability into the receptor chamber and skin layers compared to microneedle poration and untreated skin (p < 0.05). Both fractional ablative laser and polymeric microneedles markedly enhanced in vitro transdermal delivery of methotrexate into and across skin. Graphical Abstract ᅟ.

Adherence to methotrexate in rheumatoid arthritis

DEFF Research Database (Denmark)

Bliddal, Henning; Eriksen, Stine A; Christensen, Robin

2015-01-01

Objectives. To study adherence to methotrexate (MTX) and factors of importance thereof in patients with rheumatoid arthritis (RA). Methods. Patients with a hospital diagnosis of RA (ICD10 codes M05.X or M06.X) after January 1, 1997, and aged ≥18 years at the date of first diagnosis...

Enhancement effect of irradiation by methotrexate

International Nuclear Information System (INIS)

Shehata, W.M.; Meyer, R.L.

1980-01-01

Three cases are described in which complications developed which were believed to be due to the enhancement effect of irradiation by methotrexate during the course of therapy for lung, kidney, and bladder cancer. These included esophageal and large bowel complications. In two of these cases, the patients improved with conservative therapy

The investigation of antimicrobial peptides expression and its related interaction with methotrexate treatment in patients with psoriasis vulgaris.

Science.gov (United States)

Ozlu, Emin; Karadag, Ayse Serap; Ozkanli, Seyma; Oguztuzun, Serpil; Akbulak, Ozge; Uzuncakmak, Tugba Kevser; Demirkan, Serkan; Akdeniz, Necmettin

2017-12-01

Psoriasis is a chronic, inflammatory and immune-mediated disease. Recently, the role of antimicrobial peptides (AMPs) such as human beta defensins (hBDs) in the pathogenesis of psoriasis has been investigated. We aimed to evaluate the expression profiles of hBD-1 and hBD-2 in psoriatic skin before and after methotrexate (MTX) therapy and to compare healthy controls. Immunohistochemical expressions of hBD-1 and hBD-2 were assessed in 16 patients with psoriasis vulgaris and 20 normal skin biopsies from healthy controls. The patients were administered a 12 week of MTX and skin biopsy samples were obtained from the lesional skin of the patients pre-/posttreatment and normal body of the healthy controls. The median (range) Psoriasis Area and Severity Index (PASI) value was 21.6 (8.2-27.7) before the treatment whereas; 3.05 (1-23.4) after the treatment. hBD-1 expression in psoriasis patients was significantly higher as compared to the healthy controls before treatment (p psoriasis patients and healthy controls in terms of hBD-2 expression before treatment (p > 0.05). No significant difference was observed between before-after MTX treatment in terms of hBD-1 and hBD-2 expression levels in psoriasis patients (p > 0.05). These findings suggest a role for hBD-1 in psoriasis pathogenesis. But MTX treatment does not affect on hBD-1 and hBD-2 expressions. Further studies are needed to assess the roles of these AMPs in psoriasis etiopathogenesis.

Treatment of non-Hodgkin lymphoma and mature В-cell acute leukemia in children and adolescents: data of Russian regional hospitals

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Ye. V. Samochatova

2014-07-01

Full Text Available The article presents treatment results of 233 patients (children and adolescents under 19 years old; median — 8.76 years with CD20-positive non-Hodgkin lymphomas and B-cell acute leukemia (B-NHL/B-AL received chemotherapy (BFM B-NHL 90–95 protocols or combined chemo-immunotherapy with rituximab (B-NHL-2004mab protocol. Combined chemo-immunotherapy was used for patients with Burkitt lymphoma, diffuse large cells lymphomas stage III–IV and B-AL, and included cytoreductive phase, 6 polychemotherapy (PCT courses and rituximab. PCT courses are similar to those of original BFM B-NHL90 protocol, except for the first 2 courses, where daily methotrexate dose was reduced from 5 to 1 g/m2/24 h. Rituximab infused IV 12 hours before the start of first 4 chemotherapy courses at a dose of 375 mg/m2. The data in the questionnaires form have been submitted from 28 pediatric specialized hospitals from 27 Russia regions over the past 5 years (2005–2009. Protocol with rituximab has proved to be more effective than chemotherapy alone. The authors discuss the possibility of using combined chemo-immunotherapy for the treatment of B-NHL/B-AL at regional hospitals and the prospects for further treatment results improvement in this group of tumors.

Treatment of non-Hodgkin lymphoma and mature В-cell acute leukemia in children and adolescents: data of Russian regional hospitals

Directory of Open Access Journals (Sweden)

Ye. V. Samochatova

2011-01-01

Full Text Available The article presents treatment results of 233 patients (children and adolescents under 19 years old; median — 8.76 years with CD20-positive non-Hodgkin lymphomas and B-cell acute leukemia (B-NHL/B-AL received chemotherapy (BFM B-NHL 90–95 protocols or combined chemo-immunotherapy with rituximab (B-NHL-2004mab protocol. Combined chemo-immunotherapy was used for patients with Burkitt lymphoma, diffuse large cells lymphomas stage III–IV and B-AL, and included cytoreductive phase, 6 polychemotherapy (PCT courses and rituximab. PCT courses are similar to those of original BFM B-NHL90 protocol, except for the first 2 courses, where daily methotrexate dose was reduced from 5 to 1 g/m2/24 h. Rituximab infused IV 12 hours before the start of first 4 chemotherapy courses at a dose of 375 mg/m2. The data in the questionnaires form have been submitted from 28 pediatric specialized hospitals from 27 Russia regions over the past 5 years (2005–2009. Protocol with rituximab has proved to be more effective than chemotherapy alone. The authors discuss the possibility of using combined chemo-immunotherapy for the treatment of B-NHL/B-AL at regional hospitals and the prospects for further treatment results improvement in this group of tumors.

Physicians compliance during maintenance therapy in children with Down syndrome and acute lymphoblastic leukemia

DEFF Research Database (Denmark)

Bohnstedt, C; Levinsen, M; Rosthøj, S

2013-01-01

Children with Down syndrome (DS) and acute lymphoblastic leukemia (ALL) have an inferior prognosis compared with non-DS ALL patients. We reviewed methotrexate (MTX)/mercaptopurine (6MP) maintenance therapy data for children with DS treated according to the Nordic Society of Pediatric Hematology...

Pharmacogenomics of Methotrexate Membrane Transport Pathway: Can Clinical Response to Methotrexate in Rheumatoid Arthritis Be Predicted?

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Aurea Lima

2015-06-01

Full Text Available Background: Methotrexate (MTX is widely used for rheumatoid arthritis (RA treatment. Single nucleotide polymorphisms (SNPs could be used as predictors of patients’ therapeutic outcome variability. Therefore, this study aims to evaluate the influence of SNPs in genes encoding for MTX membrane transport proteins in order to predict clinical response to MTX. Methods: Clinicopathological data from 233 RA patients treated with MTX were collected, clinical response defined, and patients genotyped for 23 SNPs. Genotype and haplotype analyses were performed using multivariate methods and a genetic risk index (GRI for non-response was created. Results: Increased risk for non-response was associated to SLC22A11 rs11231809 T carriers; ABCC1 rs246240 G carriers; ABCC1 rs3784864 G carriers; CGG haplotype for ABCC1 rs35592, rs2074087 and rs3784864; and CGG haplotype for ABCC1 rs35592, rs246240 and rs3784864. GRI demonstrated that patients with Index 3 were 16-fold more likely to be non-responders than those with Index 1. Conclusions: This study revealed that SLC22A11 and ABCC1 may be important to identify those patients who will not benefit from MTX treatment, highlighting the relevance in translating these results to clinical practice. However, further validation by independent studies is needed to develop the field of personalized medicine to predict clinical response to MTX treatment.

HER2 specific delivery of methotrexate by dendrimer conjugated anti-HER2 mAb

International Nuclear Information System (INIS)

Shukla, Rameshwer; Thomas, Thommey P; Desai, Ankur M; Kotlyar, Alina; Park, Steve J; Baker, James R Jr

2008-01-01

Herceptin, a humanized monoclonal antibody that binds to human growth factor receptor-2 (HER2), was covalently attached to a fifth-generation (G5) polyamidoamine dendrimer containing the cytotoxic drug methotrexate. The specific binding and internalization of this conjugate labeled with FITC was clearly demonstrated in cell lines overexpressing HER2 by flow cytometry as well as confocal microscopic analysis. In addition, binding and uptake of antibody conjugated dendrimers was completely blocked by excess non-conjugated herceptin. The dendrimer conjugate was also shown to inhibit the dihydrofolate reductase with similar activity to methotrexate. Co-localization experiments with lysotracker red indicate that antibody conjugate, although internalized efficiently into cells, has an unusually long residence time in the lysosome. Somewhat lower cytotoxicity of the conjugate in comparison to free methotrexate was attributed to the slow release of methotrexate from the conjugate and its long retention in the lysosomal pocket

Efficacy and Toxicity of Intrathecal Liposomal Cytarabine in First-line Therapy of Childhood Acute Lymphoblastic Leukemia

DEFF Research Database (Denmark)

Levinsen, Mette; Harila-Saari, Arja; Grell, Kathrine

2016-01-01

We investigated efficacy and toxicity of replacing conventional triple (cytarabine, methotrexate, and hydrocortisone) intrathecal therapy (TIT) with liposomal cytarabine during maintenance therapy among 40 acute lymphoblastic leukemia patients. Twenty-eight of 29 patients in the TIT arm received...

CSF drug levels for children with acute lymphoblastic leukemia treated by 5 g/m2 methotrexate. A study from the EORTC Children's Leukemia Cooperative Group.

Science.gov (United States)

Milano, G; Thyss, A; Serre Debeauvais, F; Laureys, G; Benoit, Y; Deville, A; Dutour, C; Robert, A; Otten, J; Behar, C

1990-04-01

A multicenter EORTC study was conducted in children with acute lymphocytic leukemia to determine whether 5 g/m2 of methotrexate (MTX) (24 h i.v. infusion, four cycles) is an appropriate dosage for obtaining CSF drug concentrations approaching the critical cytotoxic level of 10(-6) M. A total of 193 cycles were analyzed for 58 patients. At the end of the 24 h infusion, the mean MTX serum level was 65.27 +/- 33.11 microM; the mean CSF MTX level was 1.47 +/- 1.1 microM; no significant difference in CSF MTX levels was observed between patients with (n = 20) and those without i.v. Ara-C (n = 38). The mean CSF MTX/serum MTX ratio was 0.029 +/- 0.027. CSF drug concentrations greater than or equal to 10(-6) M were achieved in 81% of the courses. The highest level was 8.4 X 10(-6) M. Only 5% of patients failed to achieve this drug concentration in at least one cycle. No significant correlation was observed between blood and CSF MTX levels. Mean CSF MTX levels were comparable from one cycle to another.

Screening of cytoprotectors against methotrexate-induced cytogenotoxicity from bioactive phytochemicals.

Science.gov (United States)

Gu, Shaobin; Wu, Ying; Yang, Jianbo

2016-01-01

As a well known anti-neoplastic drug, the cytogenotoxicity of methotrexate (MTX) has received more attention in recent years. To develop a new cytoprotector to reduce the risk of second cancers caused by methotrexate, an umu test combined with a micronucleus assay was employed to estimate the cytoprotective effects of ten kinds of bioactive phytochemicals and their combinations. The results showed that allicin, proanthocyanidins, polyphenols, eleutherosides and isoflavones had higher antimutagenic activities than other phytochemicals. At the highest dose tested, the MTX genetoxicity was suppressed by 34.03%∼67.12%. Of all the bioactive phytochemical combinations, the combination of grape seed proanthocyanidins and eleutherosides from Siberian ginseng as well as green tea polyphenols and eleutherosides exhibited stronger antimutagenic effects; the inhibition rate of methotrexate-induced genotoxicity separately reached 74.7 ± 6.5% and 71.8 ± 4.7%. Pretreatment of Kunming mice with phytochemical combinations revealed an obvious reduction in micronucleus and sperm abnormality rates following exposure to MTX (p phytochemicals combinations had the potential to be used as new cytoprotectors.

Treatment of acute otitis media in general practice

DEFF Research Database (Denmark)

Plejdrup Hansen, Malene; Jarbol, Dorte Ejg; Gahrn-Hansen, Bente

2012-01-01

Recommendations for antibiotic treatment of acute otitis media (AOM) have changed over the years, and today many experts recommend initial observation. However, antibiotic prescribing should be considered in children aged......Recommendations for antibiotic treatment of acute otitis media (AOM) have changed over the years, and today many experts recommend initial observation. However, antibiotic prescribing should be considered in children aged...

Monitoring methotrexate-induced liver fibrosis in patients with psoriasis: utility of transient elastography

Directory of Open Access Journals (Sweden)

Cheng HS

2018-05-01

Full Text Available Harriet S Cheng,1 Marius Rademaker2 1Dermatology Service, Auckland City Hospital, Auckland, New Zealand; 2Waikato Clinical Campus, Auckland University Medical School, Hamilton, New Zealand Abstract: Increasingly, existing evidence indicates that methotrexate-associated liver injury is related to comorbid risk factors such as diabetes, alcoholism, and obesity, rather than to methotrexate itself. Despite this fact, significant effort continues to be expended in the monitoring of low-dose methotrexate in patients with psoriasis. The gold standard investigation has been liver biopsy, but this is associated with significant morbidity and mortality. As methotrexate-induced liver injury is uncommon, the risk/benefit ratio of liver biopsy has been questioned. Fortunately, a number of new technologies have been developed for the diagnosis of chronic liver disease, including transient elastography (TE. TE is a type of shear wave ultrasound elastography, which measures the speed of shear waves used to estimate hepatic tissue stiffness. Several meta-analyses show very high pooled sensitivity and specificity for the diagnosis of hepatic cirrhosis (87% and 91%, respectively in a variety of chronic liver disorders. It has a negative predictive value for cirrhosis of >90% and a positive predictive value of 75%. Recent European guidelines now advocate the use of TE as the first-line test for the assessment of fibrosis in alcohol- or hepatitis-related liver disease, including nonalcoholic fatty liver disease (NAFLD. As the prevalence of obesity and metabolic syndrome, including NAFLD, is significantly elevated in patients with psoriasis, TE may be worth considering as a routine investigation for any patient with psoriasis. Although high-quality studies comparing TE with standard liver biopsy in the monitoring of psoriatics on low-dose methotrexate are lacking, the evidence from multiple small cohort studies and case series demonstrates its effectiveness. A recent

Disease activity, physical function, and radiographic progression after longterm therapy with adalimumab plus methotrexate: 5-year results of PREMIER

NARCIS (Netherlands)

van der Heijde, Désirée; Breedveld, Ferdinand C.; Kavanaugh, Arthur; Keystone, Edward C.; Landewé, Robert; Patra, Kaushik; Pangan, Aileen L.

2010-01-01

To evaluate the efficacy and safety of initial combination treatment with adalimumab (ADA) and methotrexate (MTX) versus monotherapy with ADA or MTX during an open-label extension of PREMIER. Patients with early rheumatoid arthritis (RA) received blinded ADA plus MTX, ADA alone, or MTX alone for 2

Maintenance therapy of childhood acute lymphoblastic leukemia revisited—Should drug doses be adjusted by white blood cell, neutrophil, or lymphocyte counts?

DEFF Research Database (Denmark)

Schmiegelow, Kjeld; Nersting, Jacob; Nielsen, Stine Nygaard

2016-01-01

BACKGROUND: 6-Mercaptopurine (6MP) and methotrexate (MTX) based maintenance therapy is a critical phase of childhood acute lymphoblastic leukemia treatment. Wide interindividual variations in drug disposition warrant frequent doses adjustments, but there is a lack of international consensus on dose...... levels of 6-thioguanine nucleotides or MTX (including its polyglutamates) to be significant relapse predictors. The parameters significantly associated with risk of relapse (N = 83) were male sex (hazard ratio [HR] 2.0 [1.3-3.1], P = 0.003), WBC at diagnosis (HR = 1.04 per 10 × 10(9) /l rise [1...

Outpatient treatment for acute uncomplicated diverticulitis

NARCIS (Netherlands)

Ünlü, Çagdas; Gunadi, Patrick M.; Gerhards, Michael F.; Boermeester, Marja A.; Vrouenraets, Bart C.

2013-01-01

Traditionally, treatment of acute diverticulitis has mostly been based on inpatient care. The question arises whether these patients can be treated on an outpatient basis as the admissions for diverticular disease have been shown to be increasing every year. We studied whether outpatient treatment

L-asparaginase treatment in acute lymphoblastic leukemia

NARCIS (Netherlands)

R. Pieters (Rob); S.P. Hunger (Stephen); J. Boos (Joachim); C. Rizzari (Carmelo); L.B. Silverman (Lewis); A. Baruchel (André); N. Goekbuget (Nicola); M. Schrappe (Martin); C.H. Pui (Ching-Hon)

2011-01-01

textabstractAsparaginases are a cornerstone of treatment protocols for acute lymphoblastic leukemia (ALL) and are used for remission induction and intensification treatment in all pediatric regimens and in the majority of adult treatment protocols. Extensive clinical data have shown that intensive

Development of brain tumor at six years after the onset of acute lymphoblastic leukemia

International Nuclear Information System (INIS)

Kumazaki, Hisami; Hanada, Ryoji; Kikuti, Akira; Ichikawa, Masataka; Yamamoto, Keiko; Aihara, Toshinori; Ogawa, Yoshihiro

1996-01-01

In October 1994, a 16-year-old boy was diagnosed as having a brain tumor in the left fronto-temporal region 5 years after completing treatment for acute lymphoblastic leukemia (ALL). The patient had been treated for ALL starting in 1988 when he was 10-year-old. He had received systemic chemotherapy and central nervous system prophylaxis, consisting of cranial irradiation (24 Gy) and intrathecal methotrexate. When the brain tumor was detected he was still in complete remission. The patient received only supportive therapy mainly for relief of increased intracranial pressure because the tumor was too large to resect in addition to being inappropriate for surgical treatment. He died in December 1994. On autopsy, pathological diagnosis of the brain tumor was anaplastic astrocytoma, which is a rare secondary malignancy though glioma is common. (author)

Adult Acute Lymphoblastic Leukemia Treatment (PDQ®)—Health Professional Version

Science.gov (United States)

Adult Acute Lymphoblastic Leukemia (ALL; also called acute lymphocytic leukemia) is an aggressive cancer that can progress quickly without treatment. Treatments include chemotherapy, radiation therapy, stem cell transplant, and targeted therapy. Get detailed information about the molecular genetics, prognosis, and treatment of ALL in this clinician summary.

Single-dose systemic methotrexate vs expectant management for treatment of tubal ectopic pregnancy: a placebo-controlled randomized trial.

Science.gov (United States)

Jurkovic, D; Memtsa, M; Sawyer, E; Donaldson, A N A; Jamil, A; Schramm, K; Sana, Y; Otify, M; Farahani, L; Nunes, N; Ambler, G; Ross, J A

2017-02-01

Methotrexate is used routinely worldwide for the medical treatment of clinically stable women with a tubal ectopic pregnancy. This is despite the lack of robust evidence to show its superior effectiveness over expectant management. The aim of our multicenter randomized controlled trial was to compare success rates of methotrexate against placebo for the conservative treatment of tubal ectopic pregnancy. This study took place in two early-pregnancy units in the UK between August 2005 and June 2014. Inclusion criteria were clinically stable women with a conclusive ultrasound diagnosis of a tubal ectopic pregnancy, presenting with a low serum beta human chorionic gonadotropin (β-hCG) level of Women were assigned randomly to a single systemic injection of either 50 mg/m 2 methotrexate or placebo. The primary outcome was a binary indicator for success of conservative management, defined as resolution of clinical symptoms and decline of serum β-hCG to women, 42 of whom were assigned to methotrexate and 38 to placebo. The arms of the study were matched in terms of age, ethnicity, obstetric history, pregnancy characteristics and serum levels of β-hCG and progesterone. The rates of success were similar for the two study arms: 83% with methotrexate and 76% with placebo. On univariate analysis, this difference was not statistically significant (χ 2 (1 degree of freedom) = 0.53; P = 0.47). On multivariate logistic regression, the serum level of β-hCG was the only covariate found to be significantly associated with outcome. The odds of failure increased by 0.15% for each unit increase in β-hCG (odds ratio, 1.0015 (95% CI, 1.0002-1.003); P = 0.02). In 14 women presenting with serum β-hCG of 1000-1500 IU/L, the success rate was 33% in those managed expectantly compared with 62% in those receiving methotrexate. This difference was not statistically significant and a larger sample size would be needed to give sufficient power to detect a difference in the

Modeling and Hemofiltration Treatment of Acute Inflammation

Directory of Open Access Journals (Sweden)

Robert S. Parker

2016-10-01

Full Text Available The body responds to endotoxins by triggering the acute inflammatory response system to eliminate the threat posed by gram-negative bacteria (endotoxin and restore health. However, an uncontrolled inflammatory response can lead to tissue damage, organ failure, and ultimately death; this is clinically known as sepsis. Mathematical models of acute inflammatory disease have the potential to guide treatment decisions in critically ill patients. In this work, an 8-state (8-D differential equation model of the acute inflammatory response system to endotoxin challenge was developed. Endotoxin challenges at 3 and 12 mg/kg were administered to rats, and dynamic cytokine data for interleukin (IL-6, tumor necrosis factor (TNF, and IL-10 were obtained and used to calibrate the model. Evaluation of competing model structures was performed by analyzing model predictions at 3, 6, and 12 mg/kg endotoxin challenges with respect to experimental data from rats. Subsequently, a model predictive control (MPC algorithm was synthesized to control a hemoadsorption (HA device, a blood purification treatment for acute inflammation. A particle filter (PF algorithm was implemented to estimate the full state vector of the endotoxemic rat based on time series cytokine measurements. Treatment simulations show that: (i the apparent primary mechanism of HA efficacy is white blood cell (WBC capture, with cytokine capture a secondary benefit; and (ii differential filtering of cytokines and WBC does not provide substantial improvement in treatment outcomes vs. existing HA devices.

Home treatment for acute psychiatric illness.

Science.gov (United States)

Dean, C; Gadd, E M

1990-11-03

To determine the factors influencing the successful outcome of community treatment for severe acute psychiatric illnesses that are traditionally treated in hospital. All patients from a single electoral ward who were either admitted to hospital or treated at home over a two year period (1 October 1987 to 30 September 1989) were included in the study and their case notes audited. The second year of the study is reported. Electoral ward of Sparkbrook, Birmingham. 99 Patients aged 16-65 with severe acute psychiatric illness. 65 Patients were managed by home treatment alone; 34 required admission to hospital. The location of treatment was significantly (all p less than 0.05) influenced by social characteristics of the patients (marital state, age (in men), ethnicity, and living alone) and by characteristics of the referral (occurring out of hours; assessment taking place at hospital or police station). DSM-III-R diagnosis was more weakly associated with outcome. Violence during the episode was significantly related to admission, although deliberate self harm was not. Home treatment is feasible for most patients with acute psychiatric illness. A 24 hour on call assessment service increases the likelihood of success because admission is determined more strongly by social characteristics of the patient and the referral than by illness factors. Admission will still be required for some patients. A locally based mental health resource centre, a 24 hour on call service, an open referral system, and an active follow up policy increase the effectiveness of a home treatment service.

Carrier-bound Methotrexate. IV. Antiproliferative Activity of ...

African Journals Online (AJOL)

NJD

Polymeric conjugates of methotrexate (MTX) with macromolecular carriers, ... The water-soluble conjugates, crudely fractionated by aqueous dialysis, possess mass-average molecular masses in ..... for 20 h in an ice bath and another 3 h at room temperature. ... with excess Et2O-hexane (2:1) afforded a resinous product,.

Acute Rotavirus-Induced Diarrhea in Children: Clinical Picture, Diagnosis, Treatment

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S.L. Niankovskyi

2015-09-01

Full Text Available The paper considers the current aspects of epidemiology, diagnosis, clinical picture and treatment of acute rotavirus-induced diarrhea in children. There are presented the basic thesis of ESPGHAN consensus (2014 about acute diarrheas. There was analyzed the effectiveness of probiotic Subalin producing interferon for the treatment of acute rotavirus-induced diarrhea. It was demonstrated its effectiveness according to the literature review and own data.

Effectiveness of modified hyper-CVAD chemotherapy regimen in the treatment of adult acute lymphoblastic leukemia: a retrospective experience.

Science.gov (United States)

Jalaeikhoo, Hasan; Rajaeinejad, Mohsen; Keyhani, Manoutchehr; Zokaasadi, Mohammad; Dehghani Firoozabadi, Mohammad Mehdi

2018-03-01

Several chemotherapy regimens have been developed for the treatment of acute lymphoblastic leukemia (ALL), but relapse still presents the most common obstacles to attaining long-term survival. The hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and prednisolone)/HD MTX and Ara-C (high-dose methotrexate and cytarabine) chemotherapy regimen was first started in the MD Anderson Cancer Center as an intensive regimen for adult patients with ALL. The purpose of this study was to evaluate the effectiveness of a modified hyper-CVAD protocol. We used hyper-CVAD as consolidation/maintenance after remission induction with daunorubicin, vincristine, and prednisolone (and cyclophosphamide for T-cell ALL only) rather than standard hyper-CVAD in order to reduce treatment complications. This study was conducted as a retrospective review of medical records of ALL patients at 501 army hospital, Tehran, Iran, from 2005 to 2015. Three hundred and one patients underwent modified hyper-CVAD chemotherapy regimen. Complete remission and overall survival (OS) rates were measured as primary endpoints. Two hundred and forty-six (81.7%) reached complete remission (CR) during the first 6 months of treatment, and 55 patients (18.3%) did not reach CR. The 5-year OS rate was 51.8% (95% CI (confidence interval): 45.1-57.8%). Modified hyper-CVAD regimen is an efficient intensive chemotherapy regimen for consolidation/maintenance of adults with newly diagnosed ALL and has an acceptable 5-year overall that is comparable to standard hyper-CVAD regimen. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Bisphosphonate-associated osteonecrosis of jaw reoccurrence after methotrexate therapy: a case report.

Science.gov (United States)

Alsalleeh, Fahd; Keippel, Jeffery; Adams, Lyde; Bavitz, Bruce

2014-09-01

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a well-known complication caused by amino-bisphosphonate therapy. We document one case of BRONJ associated with oral administration of methotrexate, a known immunosuppressive drug used to treat rheumatoid arthritis. A 66-year-old woman was referred for evaluation and endodontic surgery of recently re-treated tooth 13. Tooth 14 was extracted 3 months prior, and the extraction site had not completely healed. Her medical history revealed rheumatoid arthritis and osteoporosis. She had been taking Fosamax (alendronate) 70 mg daily. Because of adequate root canal therapy of tooth 13, endodontic surgery was performed. Five months after apicoectomy, her symptoms had not changed. Tooth 13 was extracted, and the socket healed without complications. The socket of extracted tooth 14 was also healing. At the 3-month recall visit, bone exposure and purulent discharge at the site of extracted tooth 14 were noted. The patient had recently received methotrexate. The methotrexate was discontinued, and she was given course of amoxicillin. At the 18-month follow-up, the healing progressed, and the wound was closed. A medication that suppresses the immune system such as methotrexate may complicate the management of BRONJ. Once a diagnosis of BRONJ is made, a closely monitored conservative approach is recommended. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

EFFECACY OF PULSE-THERAPY WIHT GLUCOCORTICOSTEROIDS AND METHOTREXATE IN PATIENTS WITH RHEUMATOID ARTHRITIS

Directory of Open Access Journals (Sweden)

N YU Lashina

2000-01-01

Full Text Available Summary Aim of study: Comparative study of clinical efficacy and tolerability of pulse-therapy (PT by glucocorticosteroids and methotrexate in RA pts and frequency of side effects and aggravations. Material and methods: 31 pts with seropositive RA (M:F=4:27 with disease activity 2-3 were examined. 16 pts had pulse-therapy by dexaven in dosage of 2 mg/kg of weight for 3 consecutive days, 15 pts of the 2nd group had methypred in classic dose of1000 mg No3. After PT on the 7th and 30th day pts had PT by methotrexate 100 mg and dexaven 16 mg. Therapy effect was evaluated after PT, in a month, 6 month and a year. During examination the following parameters were registered: severity of arthralgia, morning stiffness duration, grip strength, number of inflamedjoints, Ritchie's, Li, Landsbery indices, extra-articular manifestations. ESR, hemoglobin content, leukocytes, fibrinogen, seromucoid, C-reactive protein, CIC, RF were determined. Results: After PT in both groups arthralgia, morning stiffness, number of inflamed joints considerably subsided. Dynamics of medial indices of activity decreased by 2-3 times. Side effects after the procedures were minimal and were stopped without additional treatment.

Leflunomide and methotrexate reduce levels of activated matrix metalloproteinases in complexes with α2 macroglobulin in serum of rheumatoid arthritis patients

NARCIS (Netherlands)

Tchetverikov, I.; Kraan, M.C.; El, B. van; Hanemaaijer, R.; Groot, J. de; Huizinga, T.W.J.

2008-01-01

Objective: To analyse the effects of leflunomide and methotrexate treatment on matrix metalloproteinase (MMP) activity levels in a2 macroglobulin/MMP (α2M/MMP) complexes in the systemic circulation of rheumatoid arthritis (RA) patients. Methods: A total of 102 RA patients from a prospective,

Birth outcomes after preconception paternal exposure to methotrexate

DEFF Research Database (Denmark)

Winter, Rachel W; Larsen, Michael Due; Magnussen, Bjarne

2017-01-01

BACKGROUND: Methotrexate (MTX), a folic acid antagonist, is often prescribed for moderate to severe inflammatory related diseases. The safety of paternal MTX use prior to conception is unknown. This study, using the National Danish Registries, aimed to examine the association between paternal MTX...

Methotrexate: the emerging drug of choice for serious rheumatoid arthritis.

Science.gov (United States)

Salach, R H; Cash, J M

1994-01-01

The recently recognized high morbidity and unexpected mortality associated with rheumatoid arthritis (RA) has spurred new interest in more aggressive, early treatment of this disease. Methotrexate (MTX) has rapidly become the rheumatologist's drug of choice for serious RA because of its favorable efficacy to toxicity ratio and rapid onset of action compared with other second-line agents. The initial concerns about hepatic fibrosis and cirrhosis in psoriatic patients has subsided somewhat as long-term liver toxicity data are accumulating in patients with RA. Routine liver biopsy with incremental doses of MTX is no longer recommended. Potential for severe lung, hematologic, and infectious complications exists, mandating careful monitoring of RA patients taking MTX.

Interaction of nonsteroidal anti-inflammatory drugs with multidrug resistance protein (MRP) 2/ABCC2- and MRP4/ABCC4-mediated methotrexate transport.

NARCIS (Netherlands)

El-Sheikh, A.A.K.; Heuvel, J.J.M.W. van den; Koenderink, J.B.; Russel, F.G.M.

2007-01-01

Methotrexate (MTX) has been used in combination with nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of inflammatory diseases as well as malignancies. Especially at high MTX dosages, severe adverse effects with this combination may occur, usually resulting from an impaired renal

Protection of the Peyer's patch-associated crypt and villus epithelium against methotrexate-induced damage is based on its distinct regulation of proliferation

NARCIS (Netherlands)

Renes, Ingrid B.; Verburg, Melissa; Bulsing, Nathalie P.; Ferdinandusse, Sacha; Büller, Hans A.; Dekker, Jan; Einerhand, Alexandra W. C.

2002-01-01

The crypt and villus epithelium associated with Peyer's patches (PPs) is largely spared from methotrexate (MTX)-induced damage, compared with the non-patch (NP) epithelium. To assess the mechanism(s) preventing damage to the PP epithelium after MTX treatment, epithelial proliferation, apoptosis, and

[Effect of IV hydration with sodium bicarbonate on high-dose methotrexate disposition kinetics].

Science.gov (United States)

Tsuda, N; Goto, M; Konishi, H; Yamashina, H

1984-04-01

Following two-compartment kinetic analysis, the effect of loading of transfusion with sodium bicarbonate on methotrexate disposition was investigated in 13 cases with malignant tumor, being treated with high-dose methotrexate. The mean values of total body clearance, when administered at doses 50 mg and 100 mg per kg body weight, were 0.369 and 0.402 (l/h) per kg, respectively. No significant relationship was observed between alpha value and total amount of transfusion, of urine or dosage of sodium bicarbonate. The other kinetic parameters on elimination, beta value, K10 and total body clearance, did not also correlate with those values described above. These results suggest that the elimination profile of methotrexate show linear kinetics, and that massive administration of transfusion with sodium bicarbonate be not necessary if pH value of urine exceeds 7.0.

Sequence-dependent toxicity profile in modified FAMTX (fluorouracil-adriamycin-methotrexate) chemotherapy with lenograstim support for advanced gastric cancer: a feasibility study

NARCIS (Netherlands)

Westermann, A. M.; Taal, B. G.; Swart, M.; Boot, H.; Craanen, M.; Gerritsen, W. R.

2000-01-01

For advanced irresectible gastric cancer, sequential high-dose methotrexate and 5-fluorouracil (both on day 1) combined with adriamycin on day 15 (FAMTX regimen), cycled every 28 days, is a fairly effective but toxic treatment, with a high incidence of neutropenic fever, dose reductions and dose

Utilization of Subcutaneous Methotrexate in Rheumatoid Arthritis Patients After Failure or Intolerance to Oral Methotrexate: A Multicenter Cohort Study.

Science.gov (United States)

Branco, Jaime C; Barcelos, Anabela; de Araújo, Filipe Pombo; Sequeira, Graça; Cunha, Inês; Patto, José Vaz; Oliveira, Margarida; Mateus, Margarida Pratas; Couto, Maura; Nero, Patrícia; Pinto, Patrícia; Monteiro, Paulo; Castelão, Walter; Félix, Jorge; Ferreira, Diana; Almeida, João; Silva, Maria João

2016-01-01

Low-dose weekly methotrexate (MTX) is the mainstay in the therapy of rheumatoid arthritis (RA). It can be given via oral, intramuscular or subcutaneous (SC) route. This study sought to determine the real-world pattern of treatment with SC MTX in Portuguese adult patients with active RA. Utilization of Metoject(®) in Rheumatoid Arthritis (UMAR) was a non-interventional, cohort multicenter study with retrospective data collection. Eligible patients had active RA, at least 18 years of age, and started SC MTX treatment in 2009 or 2010 after failure or intolerance to oral MTX. Data were collected from patient's clinical records. Both non-parametric and parametric survival methods were used to obtain a detailed understanding of SC MTX treatment duration. Fifty patients were included, of which only 9 discontinued SC MTX during the study follow-up period. The probability of discontinuation after 1, 2, and 3 years of treatment of SC MTX treatment is expected to be 6.10%, 8.50%, and 23.20%, respectively. The extrapolated median duration of SC MTX using an exponential model was 106.4 months/8.87 years. Mean dose of SC MTX was 18.36 mg. The reasons for treatment discontinuation were occurrence of adverse events in six patients and lack of efficacy in three. The long treatment duration of SC MTX highlights its excellent tolerability compared to oral MTX, especially concerning the frequent adverse gastrointestinal events of MTX. Furthermore, long MTX treatment duration provides the opportunity to postpone or even avoid expensive therapies with biologics. The results obtained from the UMAR study provide important information for the utilization and public financing of SC MTX in Portugal.

DNA-thioguanine nucleotide concentration and relapse-free survival during maintenance therapy of childhood acute lymphoblastic leukaemia (NOPHO ALL2008)

DEFF Research Database (Denmark)

Nielsen, Stine Nygaard; Grell, Kathrine; Nersting, Jacob

2017-01-01

BACKGROUND: Adjustment of mercaptopurine and methotrexate maintenance therapy of acute lymphoblastic leukaemia by leucocyte count is confounded by natural variations. Cytotoxicity is primarily mediated by DNA-incorporated thioguanine nucleotides (DNA-TGN). The aim of this study was to establish w...

Application of nasointestinal feeding tube in treatment of acute pancreatitis

Directory of Open Access Journals (Sweden)

Li Tian

2016-12-01

Full Text Available Objective: To observe the clinical effect of nasointestinal feeding tube for enteral nutrition in the treatment of acute pancreatitis. Methods: A total of 128 patients with acute pancreatitis who were admitted in our hospital were included in the study and randomized into the treatment group and the control group with 64 cases in each group. Routine pancreatitis treatments after admission in the two groups were performed. On the basis, nasointestinal feeding tube was indwelled in patients in the treatment group for nutrition support. The changes of biochemical and nutritional indicators before and after treatment in the two groups were compared. Results: LC, TP, ALB, and Hb after treatment in the two groups were significantly elevated, while AMY and Lipase were significantly reduced when compared with before treatment (P0.05. Conclusions: Adoption of nasointestinal feeding tube for enteral nutrition in the treatment of acute pancreatitis can significantly improve the nutritional status; therefore, it deserves to be widely recommended in the clinic.

[Acute lithium poisoning: epidemiology, clinical characteristics, and treatment].

Science.gov (United States)

Burguera Vion, Víctor; Montes, José Manuel; Del Rey, José Manuel; Rivera-Gorrín, Maite; Rodao, José María; Tenorio, Maite; Saiz-Ruiz, Jerónimo; Liaño, Fernando

2017-02-01

Lithium continues to be the treatment of choice for bipolar disorder. Acute lithium poisoning is a potentially serious event. We present a retrospective observational significative study of episodes of acute lithium poisoning during a 52- month period. Poisoning was defined by a blood lithium concentration of 1.5 mEq/L or higher. We analyzed treatment and epidemiologic and clinical characteristics of 70 episodes were identified (incidence density among treated patients, 1.76 per 100 patient-years). The most frequent cause of lithium poisoning was a concurrent medical condition (46%). Most poisonings were mild (74.2%), but neurologic involvement was identified in 40.3%. Electrocardiographic abnormalities were found in 8 cases. Acute renal failure, found in 23 patients (37.1%), was mild in most cases, although 11 patients required hemodialysis. We concluded that acute lithium poisoning is an uncommon complication, but risk needs to be lowered. Patients should be warned to avoid dosage errors and to take special care during concurrent illnesses and while taking other medications.

Clinical Study on Prospective Efficacy of All-Trans Acid, Realgar-Indigo Naturalis Formula Combined with Chemotherapy as Maintenance Treatment of Acute Promyelocytic Leukemia

Directory of Open Access Journals (Sweden)

Li Xiang-Xin

2014-01-01

Full Text Available Objectives. To test the efficiency and safety of sequential application of retinoic acid (ATRA, Realgar-Indigo naturalis formula (RIF and chemotherapy (CT were used as the maintenance treatment in patients with acute promyelocytic leukemia (APL. Methods. This was a retrospective study of 98 patients with newly diagnosed APL who accepted two different maintenance treatments. After remission induction and consolidation chemotherapy according to their Sanz scores, patients received two different kinds of maintenance scheme. The first regimen was using ATRA, RIF, and standard dose of CT sequentially (ATRA/RIF/CT regimen, while the second one was using ATRA and low dose of chemotherapy with methotrexate (MTX plus 6-mercaptopurine (6-MP alternately (ATRA/CTlow regimen. The OS, DFS, relapse rate, minimal residual disease, and adverse reactions in two groups were monitored and evaluated. Results. ATRA/RIF/CT regimen could effectively reduce the chance of relapse in different risk stratification of patients, but there was no significant difference in 5-year DFS rate and OS rate between the two groups. Besides, the patients in the experimental group suffered less severe adverse reactions than those in the control group. Conclusions. The repeated sequential therapeutic regimen to APL with ATRA, RIF, and chemotherapy is worth popularizing for its high effectiveness and low toxicity.

Leukoencephalopathy in childhood hematopoietic neoplasm caused by moderate-dose methotrexate and prophylactic cranial radiotherapy -- an MR analysis

International Nuclear Information System (INIS)

Matsumoto, Ko; Takahashi, Shoki; Sato, Atsushi; Imaizumi, Masue; Higano, Shuichi; Sakamoto, Kiyohiko; Asakawa, Hiroshi; Tada, Keiya

1995-01-01

Purpose: The main purpose of this study was to determine influential factors related to minor leukoencephalopathy (LEP) caused by moderate-dose methotrexate (MTX) and prophylactic cranial radiotherapy (CRT) in childhood hematopoietic malignancies. We also compared the incidence of LEP following this treatment to that reported in the literature following treatment with high-dose MTX alone. Methods and Materials: Thirty-eight pediatric patients of hematopoietic malignancies (37 acute lymphoblastic leukemias, 1 non-Hodgkin lymphoma) who were given CRT (18-24 Gy) as well as prophylactic intrathecal and per os MTX were studied for leukoencephalopathy by magnetic resonance (MR) imaging. All the patients were free from grave neuropsychiatric disturbances. The data were examined to elucidate the influential ones of five factors (patients' age, doses of intrathecal and per os MTX, dose of CRT, interval between treatment, and MR study) to develop LEP using multiple regression analysis. To compare the effect of moderate-dose MTX and prophylactic CRT on LEP to that of high-dose MTX alone, we conducted literature review. Results: Seven out of 38 patients (18%) developed LEP. From multiple regression analysis and partial correlation coefficients, the age and CRT dose seemed influential in the subsequent development of LEP. The incidence of LEP following treatment with moderate-dose MTX and prophylactic CRT appears to be less than that reported in the literature following treatment with intravenous high-dose MTX. However, even moderate-dose MTX in combination with CRT can result in a significant incidence of MR-detectable LEP, particularly in children 6 years of age or younger receiving 24 Gy. Conclusion: Leukoencephalopathy was caused by moderate-dose MTX and prophylactic CRT in pediatric patients, probably less frequently than by high-dose MTX treatment alone. The influential factors were patient's age and CRT dose

Surgical treatment of acute pulmonary embolism--a 12-year retrospective analysis

DEFF Research Database (Denmark)

Lehnert, Per; Møller, Christian H; Carlsen, Jørn

2012-01-01

Surgical embolectomy for acute pulmonary embolism (PE) is considered to be a high risk procedure and therefore a last treatment option. We wanted to evaluate the procedures role in modern treatment of acute PE....

Treatment of Acute Myeloid Leukemia in Adolescent and Young Adult Patients

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Guldane Cengiz Seval

2015-03-01

Full Text Available The objectives of this review were to discuss standard and investigational treatment strategies for adolescent and young adult with acute myeloid leukemia, excluding acute promyelocytic leukemia. Acute myeloid leukemia (AML in adolescent and young adult patients (AYAs may need a different type of therapy than those currently used in children and older patients. As soon as AML is diagnosed, AYA patient should be offered to participate in well-designed clinical trials. The standard treatment approach for AYAs with AML is remission induction chemotherapy with an anthracycline/cytarabine combination, followed by either consolidation chemotherapy or stem cell transplantation, depending on the ability of the patient to tolerate intensive treatment and cytogenetic features. Presently, continuing progress of novel drugs targeting specific pathways in acute leukemia may bring AML treatment into a new era.

Ameliorative Effects of Hydroalcoholic Extract of Lavandula officinalis L. on Methotrexate-Induced Oxidative Stress in Rats

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Mojtaba Kalantar, Saeed Shirali, Amin Hasanvand , Masoud Valizadeh , Ramin Tavakoli , Marzieh Asadi , Mehdi Goudarzi

2017-03-01

Full Text Available Background: Methotrexate as a chemotherapy drug can causes chronic liver damage and oxidative stress. The aim of this study was to evaluate the protective effect of hydroalcoholic extract of Lavandula officinalis on methotrexate-induced oxidative stress in rats. Methods: In this experimental study, thirty five Wistar male rats weighting 200-250 g were randomly divided into 5 groups (n = 7 in each group. Negative control group (normal saline 5ml/kg; positive control group received normal salin orally for 10 days, and a single dose of methotrexate (MTX, 20mg/kg, i.p. was administrated on the 9th day. Groups 3-5 received respectively 100, 200 and 400 mg/kg of Lavandula officinalis extract (LOE orally for 10 days, and a single dose of MTX was injected on the 9th day. 24 h after the last injection, animals were sacrificed. Blood samples were collected to determine serum AST, ALT and ALP levels. Malondialdehyde (MDA, glutathione (GSH levels and catalase (CAT, superoxide dismutase (SOD and glutathione peroxidase (GPx activity were assayed in liver tissue. A portion of liver was maintained in 10% formalin for Hematoxylin and Eosin (H&E staining and histological examination. Results: The result obtained from current study was showed a significant increase in the levels of AST, ALT, ALP, MDA and decrease of GSH, CAT and SOD by MTX administration. Pre-treatment with LOE showed reduction in the levels of AST, ALT, ALP, MDA and increase of GSH, CAT and SOD in all doses but the most significant alteration was observed in doses of 200 and 400 mg/kg (P<0.05. Histological results showed that methotrexate could lead to liver damage. Also the hepatoprotective effect of the LOE was confirmed by the histological examination of the liver. Conclusion: Our results indicate that hydroalcoholic extract of Lavandula officinalis have produced amelioration in biochemical and oxidative stress parameters against MTX -induced oxidative stress.

Effects of methotrexate combined with hydroxychloroquine sulfate and prednisone acetate on inflammatory response, immune function and liver and renal function in patients with systemic lupus erythematosus

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Jiang-Li Xia

2017-11-01

Full Text Available Objective: To investigate the effects of methotrexate and hydroxychloroquine sulfate and prednisone on inflammatory response, immune function, liver and renal function in patients with systemic lupus erythematosus (SLE. Methods: A total of 80 cases of SLE patients according to the random data table were divided into the control group (n=40 and observation group (n=40, the control group were treated with hydroxychloroquine sulfate and prednisone treatment, on the basis of treatment of the control group, patients in the observation group in the control group were treated with methotrexate, the levels of inflammatory factors, immune function, liver and kidney function indexes in the two groups between the before treatment and after treatment were compared. Results: Comparison of the levels before treatment, the difference of the CRP, WBC, ESR, IgA, IgG, complement C3, complement C4, ALT, AST, SCr and BUN levels were not statistically significant. After treatment, the levels of CRP, ESR, IgA, IgG, ALT, AST, SCr and BUN in the observation group were significantly lower than those in the control group, and the difference was statistically significant. The levels of WBC and complement C4 in the observation group [(5.18±1.08伊10 9 /L, (0.22±0.05 g/L] were significantly higher than those in the control group [(4.51±0.52伊10 9 /L, (0.18±0.03 g/L], and there was no significant difference in the level of complement C3 between the two groups after treatment. Conclusion: Methotrexate combined with hydroxychloroquine sulfate and prednisone for the treatment of SLE can effectively reduce inflammation, improve immune function, has little effect on kidney function, high safety, which has an important clinical value.

Endovascular treatment of acute basilar artery occlusion: time to treatment is crucial

International Nuclear Information System (INIS)

Dorňák, T.; Herzig, R.; Kuliha, M.; Havlíček, R.; Školoudík, D.; Šaňák, D.; Köcher, M.; Procházka, V.; Lacman, J.; Charvát, F.; Krajina, A.

2015-01-01

Aim: To evaluate the safety and efficacy of multimodal endovascular treatment (EVT) of acute basilar artery occlusion (BAO), including bridging therapy [intravenous thrombolysis (IVT) with subsequent EVT], to compare particular EVT techniques and identify predictors of clinical outcome. Materials and methods: This retrospective, multi-centre study comprised 72 acute ischaemic stroke patients (51 males; mean age 59.1 ± 13.3 years) with radiologically confirmed BAO. The following data were collected: baseline characteristics, risk factors, pre-event antithrombotic treatment, neurological deficit at time of treatment, localization of occlusion, time to therapy, recanalization rate, post-treatment imaging findings. Thirty- and 90-day outcomes were evaluated using the modified Rankin scale with a good clinical outcome defined as 0–3 points. Results: Successful recanalization was achieved in 94.4% patients. Stepwise binary logistic regression analysis identified the presence of arterial hypertension (OR = 0.073 and OR = 0.067, respectively), National Institutes of Health Stroke Scale (NIHSS) at the time of treatment (OR = 0,829 and OR = 0.864, respectively), and time to treatment (OR = 0.556 and OR = 0.502, respectively) as significant independent predictors of 30- and 90-day clinical outcomes. Conclusion: Data from this multicentre study showed that multimodal EVT was an effective recanalization method in acute BAO. Bridging therapy shortens the time to treatment, which was identified as the only modifiable outcome predictor. - Highlights: • Various treatments are being used in recanalization of basilar artery occlusion. • Multimodal endovascular treatment is an effective recanalization method. • Time-to-treatment is the only modifiable outcome predictor. • Bridging therapy shortens time-to-treatment. • Arterial hypertension, neurologic deficit are associated with poor outcome

Uterine arterial methotrexate infusion and embolization in the treatment of uterine adenomyosis

International Nuclear Information System (INIS)

Xie Jingyan; Wang Suzheng; Chen Jingfang; Xuan Yinghua; Lou Wensheng; Gu Jianping

2008-01-01

Objective: To study the efficacy of treating different types of uterine adenomyosis with transcatheter local infusion of methotrexate (MTX) combined with uterine arterial embolization under guidance of digital subtraction angiography (DSA). Methods: 33 cases were primarily screened out according to clinical symptoms and color Doppler and then further diagnosis as diffuse or local adenomyosis were undertaken with super selective uterine arterial angiography. The patients were then treated with uterine arterial local infusion (50 mg MTX)and embolization with PVA microsphere (diameter 450-650 μm), individually. Finally, the comparison between the preoperative and postoperative menstruation volumes, the degrees of dysmenorrheal, uterine sizes and the levels of sexual hormones of diffuse and local adenomyosis was carried out. Results: The uterine arterial local infusion of MTX combined with embolization showed no chemotherapeutic side effects. In all cases, there were decrease of menstruation amount, alleviated dysmenorrhea, reduction of uterine size, and the efficacy was more evident in diffuse adenomyosis (P<0.05). Conclusions: Micro-invasive interventional technique combined with drug therapy is promising for diffuse and local adenomyosis especially for the former. (authors)

Changes of CSF-protein pattern in children with acute lymphoblastic leukemia during prophylactic CNS therapy (Berlin protocol)

International Nuclear Information System (INIS)

Siemes, H.; Rating, D.; Siegert, M.; Hanefeld, F.; Mueller, S.; Gadner, H.; Riehm, H.

1980-01-01

The cerebral spinal fluid (CSF)-protein profiles of ten children with previously untreated acute lymphoblastic leukemia (ALL) were investigated by agarose gel electrophoresis. The profiles were determined at diagnosis and during the fifth to eighth week of treatment when preventive therapy for central nervous system (CNS) leukemia (skull irradiation, intrathecal methotrexate (ithMTX) was administered. The profiles were compared with those obtained from a control group of 67 children and those from 42 patients with acute aseptic meningitis. The data from the latter group demonstrated the CSF-protein pattern of partial blood-CSF barrier (B-CSF-B) breakdown. The children with ALL showed no or only minor signs of a B-CSF-B impairment at diagnosis and after four weeks of systemic treatment. However, CSF changes indicative of a lesion of the B-CSF-B increased in all children continuously during CNS prophylaxis. The protein profile at the end of combined chemotherapy and radiotherapy was very similar to that in patients with acute aseptic meningitis. These observations point to neurotoxic side effects on the CNS barrier system with the combination of cranial radiation and ithMTX. A striking finding was restricted heterogeneity of gamma-globulin, observed in the CSF of nine out of the ten children with ALL before or during treatment. The significance of this abnormality is unknown

Enhanced antitumor efficacy of poly(D,L-lactide-co-glycolide-based methotrexate-loaded implants on sarcoma 180 tumor-bearing mice

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Gao L

2017-10-01

Full Text Available Li Gao,1,2 Lunyang Xia,3 Ruhui Zhang,1 Dandan Duan,3 Xiuxiu Liu,2 Jianjian Xu,2 Lan Luo1 1State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 2School of Biological and Medical Engineering, Hefei University of Technology, Hefei, 3Laboratory of Pharmaceutical Research, Anhui Zhongren Science and Technology Co., Ltd., Hefei, People’s Republic of China Purpose: Methotrexate is widely used in chemotherapy for a variety of malignancies. However, severe toxicity, poor pharmacokinetics, and narrow safety margin of methotrexate limit its clinical application. The aim of this study was to develop sustained-release methotrexate-loaded implants and evaluate antitumor activity of the implants after intratumoral implantation. Materials and methods: We prepared the implants containing methotrexate, poly(D,L-lactide-co-glycolide, and polyethylene glycol 4000 with the melt-molding technique. The implants were characterized with regards to drug content, morphology, in vitro, and in vivo release profiles. Differential scanning calorimetry (DSC and Fourier transform infrared spectroscopy (FTIR were carried out to investigate the physicochemical properties of the implants. Furthermore, the antitumor activity of the implants was tested in a sarcoma 180 mouse model. Results: The implants were prepared as solid rods. Scanning electron microscopy images showed a smooth surface of the implant, suggesting that methotrexate was homogeneously dispersed in the polymeric matrix. The results of DSC and FTIR indicated that no significant interaction between methotrexate and the polymer was observed in the implants. Both in vitro and in vivo release profiles of the implants were characterized by burst release followed by sustained release of methotrexate. Intratumoral implantation of methotrexate-loaded implants could efficiently delay tumor growth. Moreover, an increase in the dose of implants led to a higher tumor

Pure methotrexate encephalopathy presenting with seizures: CT and MRI features

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Loevblad, K.O.; Kelkar, P.; Ozdoba, C.; Remonda, L.; Schroth, G. [Department of Neuroradiology, Institute of Diagnostic Radiology, Inselspital, University of Bern, CH-3010 Bern (Switzerland); Ramelli, G. [Department of Pediatrics, Inselspital, University of Bern, Bern (Switzerland)

1998-02-01

With the advent of chemotherapy, mortality rates in acute lymphoblastic leukaemia (ALL) have decreased, but complications in the central nervous system have appeared. These include direct involvement of the brain itself and the development of chemotherapy-related encephalopathy as a delayed reaction. In most reported cases, this encephalopathy is believed to be due to necrotising angiitis arising from the combination of chemotherapy with adjuvant radiotherapy. We report the cases of four children with ALL who had been treated with high-dose intravenous and intrathecal chemotherapy but no radiation therapy, and who were admitted to hospital because of seizures. CT of the brain revealed the presence of diffuse periventricular white matter hypodensities in all cases and subcortical hyperdense foci in three cases. MRI showed diffuse hyperintense white matter lesions on T2-weighted images in all four patients; hypointense changes were observed on susceptibility-sensitive FLASH sequences in the hyperdense foci seen on CT as well as changes that were hyperintense on T1-weighted images. It was, therefore, concluded that the lesions corresponded to a leukoencephalopathy with calcific deposits. These findings are of a pure form of methotrexate encephalopathy causing seizures. (orig.) With 2 figs., 17 refs.

Pure methotrexate encephalopathy presenting with seizures: CT and MRI features

International Nuclear Information System (INIS)

Loevblad, K.O.; Kelkar, P.; Ozdoba, C.; Remonda, L.; Schroth, G.; Ramelli, G.

1998-01-01

With the advent of chemotherapy, mortality rates in acute lymphoblastic leukaemia (ALL) have decreased, but complications in the central nervous system have appeared. These include direct involvement of the brain itself and the development of chemotherapy-related encephalopathy as a delayed reaction. In most reported cases, this encephalopathy is believed to be due to necrotising angiitis arising from the combination of chemotherapy with adjuvant radiotherapy. We report the cases of four children with ALL who had been treated with high-dose intravenous and intrathecal chemotherapy but no radiation therapy, and who were admitted to hospital because of seizures. CT of the brain revealed the presence of diffuse periventricular white matter hypodensities in all cases and subcortical hyperdense foci in three cases. MRI showed diffuse hyperintense white matter lesions on T2-weighted images in all four patients; hypointense changes were observed on susceptibility-sensitive FLASH sequences in the hyperdense foci seen on CT as well as changes that were hyperintense on T1-weighted images. It was, therefore, concluded that the lesions corresponded to a leukoencephalopathy with calcific deposits. These findings are of a pure form of methotrexate encephalopathy causing seizures. (orig.)

Folate, homocysteine, and cobalamin status in patients with rheumatoid arthritis treated with methotrexate, and the effect of low dose folic acid supplement

DEFF Research Database (Denmark)

Hornung, Nete; Ellingsen, Torkell; Stengaard-Pedersen, Kristian

2004-01-01

OBJECTIVE: To investigate the effect of methotrexate (MTX) treatment of rheumatoid arthritis (RA) on folate metabolism, and to determine the effect of low dose folic acid on toxicity, efficacy, and folate status. METHODS: A 52-week prospective study of 81 patients with RA treated with MTX and self...

Clinical treatment, care and prognosis. Acute leukemia after treatment and other malignant illness

International Nuclear Information System (INIS)

Mulder, N.H.; Houwen, B.

1978-01-01

The authors describe research results on five patients suffering from acute leukemia. In each case the first diagnosis is given, followed by the treatment, and a second diagnosis is quoted after an interval of a few years. One patient had cancer of neck and breast and two had Hodgkins disease according to the first diagnosis. In each case the second diagnosis was acute or smouldering leukemia. The treatments applied include radiotherapy, some surgery and applications of drugs. Details are given for each case in turn. (G.C.)

Clinical treatment, care and prognosis. Acute leukemia after treatment and other malignant illness

Energy Technology Data Exchange (ETDEWEB)

Mulder, N H; Houwen, B [Rijksuniversiteit Groningen (Netherlands). Academisch Ziekenhuis

1978-03-25

The authors describe research results on five patients suffering from acute leukemia. In each case the first diagnosis is given, followed by the treatment, and a second diagnosis is quoted after an interval of a few years. One patient had cancer of neck and breast and two had Hodgkins disease according to the first diagnosis. In each case the second diagnosis was acute or smouldering leukemia. The treatments applied include radiotherapy, some surgery and applications of drugs. Details are given for each case in turn.

Comparing ultraviolet light A photo(chemo)therapy with Methotrexate protocol in childhood localized scleroderma: Evidence from systematic review and meta-analysis approach.

Science.gov (United States)

Marrani, Edoardo; Foeldvari, Ivan; Lopez, Jordi Anton; Cimaz, Rolando; Simonini, Gabriele

2018-03-14

Localized scleroderma is a skin fibrosing disorder that, if untreated, may result in severe disability. The purpose of this systematic review is to compare the present evidence concerning the effectiveness of Methotrexate versus phototherapy, alone or associated with Psoralen, in childhood localized scleroderma. A systematic search between January 1996 and May 2017 was performed to identify studies investigating the efficacy of Methotrexate (MTX) or phototherapy (UVA) for treating localized scleroderma with onset ≤18 years. Due to a lack of validated clinical criteria, four clinical response criteria were used to assess the treatment efficacy as primary outcome. We determined a combined estimate of the proportion of children responding to MTX and UVA. A total of 19 studies was included (8 MTX; 11 UVA). In the methotrexate group, 193 children were included in the analysis; in the phototherapy group, a total of 48 treated children. For both groups age, disease subtype, glucocorticoids (GCs) use, and side effects of treatment were also analyzed. The meta-analysis suggested that UVA and MTX protocols have both a favorable effect in active lesions of childhood localized scleroderma. However, MTX resulted significantly superior to UVA, with or without Psoralen. Our study supports the combination of MTX and GCs in patients with a high risk of complication. Phototherapy with UVA1 could represent a therapeutic option in patients with limited scleroderma, where lesions do not cross joints and they do not lead to potential cosmetic changes. Copyright © 2018 Elsevier Inc. All rights reserved.

A case of acute lymphoblastic leukemia with an intracerebellar mass

International Nuclear Information System (INIS)

Oshima, Yukio; Shitara, Toshiji; Kuribayashi, Toshio; Noji, Takashi; Kuroume, Takayoshi

1983-01-01

A 3-year-old boy, who had a complaint of hemorrhagic diathesis, was diagnosed as having acute lymphoblastic leukemia. Remission was induced by a combination of vincristine and prednisolone. Prophylactic intrathecal methotrexate and cranial irradiation were administered. Two years later, he was hospitalized for CNS leukemia and treated with multiple doses of intrathecal methotrexate. At the time, the results of CT scanning were normal. Six months later, though, he developed vomiting and lethargy. CT scanning showed a mass of an increased density in the right cerebellar hemisphere that displaced the fourth ventricle to the left and resulted in an obstructive hydrocephalus. Decompression was done by means of Ommaya reservoir setting. Soon his consciousness returned to normal, and CT scanning revealed no abnormal mass three weeks later. A month later, though, the CNS leukemia returned. He developed vomiting and a headache, and CT scanning showed a high-density mass in the right cerebellar hemisphere. The mass was diagnosed as hematoma. He died one month later. In this case, the previous mass showed evidence of a relatively uniform contrast enhancement, which is consistent with the intracerebral leukemic mass reported by Wendling. In Japan, this is the first report of an intracerebellar mass of acute lymphoblastic leukemia as perceived by CT scanning. (author)

Generalized anxiety disorder: acute and chronic treatment.

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Rynn, Moira A; Brawman-Mintzer, Olga

2004-10-01

Clinical and epidemiological data suggest that generalized anxiety disorder (GAD) is a chronic illness causing patients to suffer for many years leading to significant distress in daily life functioning. The literature suggests the several conclusions. GAD is a disorder in need of appropriate treatment and often has a chronic course with comorbid conditions, such as major depression and other anxiety disorders. Benzodiazepines, while effective anxiolytic agents acutely, when prescribed for >4 weeks cause rebound anxiety and following prolonged therapy may lead to withdrawal symptoms. Antidepressants cause significant anxiety relief compared with placebo and for psychosocial treatment cognitive-behavioral therapy is an efficacious psychosocial treatment. Many GAD patients are in need of long-term medication management. Furthermore, there is limited data for patients diagnosed with GAD the treatment outcome with the combination of medication and psychotherapy both acutely and long-term; how to best sequence these treatments; for those patients who do not meet remission criteria what is the ideal approach for augmentation; and for patients with treatment-refractory GAD the empirical evidence is lacking on medication switching and augmentation strategies. Research is needed in the area of developing treatment strategies for patients suffering from treatment-refractory GAD. There is still an urgent need to explore treatment combinations and duration strategies in the management of patients suffering with GAD.

The acute and preventative treatment of episodic migraine

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Sarah Miller

2012-01-01

Full Text Available Episodic migraine is a common debilitating condition with significant worldwide impact. An effective management plan must include acute treatment to relieve the pain and potential disability associated with the attacks and may also include preventative treatments with an aim of decreasing attack frequency and severity in the longer term. Acute treatments must be limited to a maximum of 2-3 days a week to prevent medication overuse headache and focus on simple analgesia, non-steroidal anti-inflammatory drugs and triptans. Preventative treatments are numerous and should be considered when migraine attacks are frequent and or disabling, acute medication is failing, in special circumstances such as hemiplegic migraines or if the patient requests them. All preventative medications must be given at therapeutic doses for at least 6-8 weeks before an adequate trial can be judged ineffective. The most important factor in choosing drugs is the patient and the clinical features of their attack and treatment should be tailored to these. Relative co-morbidities will influence drug choice, as will the side effect profile and the efficacy of the drug. First line preventative drugs include ß-blockers, amitriptyline and anti-epileptic drugs such as topiramate and valproate. Drugs with lower efficacy or poorer side effect profiles include selective serotonin reuptake inhibitors (SSRIs, calcium channel antagonists, gabapentin and herbal medicines.

Methotrexate for the treatment of juvenile idiopathic arthritis: process to approval for JIA indication in Japan.

Science.gov (United States)

Mori, Masaaki; Naruto, Takuya; Imagawa, Tomoyuki; Murata, Takuji; Takei, Syuji; Tomiita, Minako; Itoh, Yasuhiko; Fujikawa, Satoshi; Yokota, Shumpei

2009-01-01

Methotrexate (MTX), the primary treatment for the articular-type juvenile idiopathic arthritis (JIA), is effective and brings about radiological improvement. Patient compliance is good, and it is recognized that its known side effects, namely, disruption of liver function and induction of pulmonary lesions, are unlikely to be severe at the low MTX doses that are administered. In Japan, MTX was granted approval in 1999 by the then Ministry of Health and Welfare specifically for treating rheumatoid arthritis in adult patients, allowing it be generally used in medical institutions for patients having National Health Insurance. However, in the pediatric field, its use outside the indications has so far been unavoidable, and has been left to the discretion of the physician. Finally, at the present conference, expansion of the indications of MTX for JIA was approved in Japan. It is noteworthy that this expansion of indications was achieved without requiring clinical trials on children sponsored by the pharmaceutical company: it was achieved rather by collecting necessary information through ongoing efforts (including collection and analysis of information about approval status in foreign countries, adequate evidence from the literature, implementation of a clinical use survey in Japan, etc.). It also merits attention that the maximum dose (10 mg/m2) was set on the basis of pharmacokinetic data from children, rather than relying on the dosing method and dose for adults.

Determinants for drug survival of methotrexate in patients with psoriasis, split according to different reasons for discontinuation: results of the prospective MTX-CAPTURE

NARCIS (Netherlands)

Otero, M.E.; Reek, J.M.P.A. van den; Seyger, M.M.B.; Kerkhof, P.C.M. van de; Kievit, W.; Jong, E.M.G.J. de

2017-01-01

BACKGROUND: As methotrexate (MTX) is a widely used treatment for psoriasis, it is important to gain insight into the reasons for the discontinuation of MTX and to understand the determinants for drug survival. OBJECTIVES: To describe 5-year drug survival for MTX in patients with psoriasis, split

A systematic review on the treatment of acute ankle sprain: brace versus other functional treatment types.

Science.gov (United States)

Kemler, Ellen; van de Port, Ingrid; Backx, Frank; van Dijk, C Niek

2011-03-01

Ankle injuries, especially ankle sprains, are a common problem in sports and medical care. Ankle sprains result in pain and absenteeism from work and/or sports participation, and can lead to physical restrictions such as ankle instability. Nowadays, treatment of ankle injury basically consists of taping the ankle. The purpose of this review is to evaluate the effectiveness of ankle braces as a treatment for acute ankle sprains compared with other types of functional treatments such as ankle tape and elastic bandages. A computerized literature search was conducted using PubMed, EMBASE, CINAHL and the Cochrane Clinical Trial Register. This review includes randomized controlled trials in English, German and Dutch, published between 1990 and April 2009 that compared ankle braces as a treatment for lateral ankle sprains with other functional treatments. The inclusion criteria for this systematic review were (i) individuals (sports participants as well as non-sports participants) with an acute injury of the ankle (acute ankle sprains); (ii) use of an ankle brace as primary treatment for acute ankle sprains; (iii) control interventions including any other type of functional treatment (e.g. Tubigrip™, elastic wrap or ankle tape); and (iv) one of the following reported outcome measures: re-injuries, symptoms (pain, swelling, instability), functional outcomes and/or time to resumption of sports, daily activities and/or work. Eight studies met all inclusion criteria. Differences in outcome measures, intervention types and patient characteristics precluded pooling of the results, so best evidence syntheses were conducted. A few individual studies reported positive outcomes after treatment with an ankle brace compared with other functional methods, but our best evidence syntheses only demonstrated a better treatment result in terms of functional outcome. Other studies have suggested that ankle brace treatment is a more cost-effective method, so the use of braces after acute

The treatment of acute soft tissue trauma in Danish emergency rooms

DEFF Research Database (Denmark)

Johannsen, F; Langberg, Henning

1997-01-01

Rest, ice, compression, elevation (RICE) is the most recommended treatment for acute traumatic soft tissue injuries. A questionnaire was given to all Danish emergency rooms (n = 5) regarding their routines for acute treatment of ankle sprains and muscle contusions. Complete answers were received...... from 37 emergency rooms (73%), covering the treatment of 111 ankle sprains and 101 muscle contusions. Treatment with RICE was given in a minority of injuries, ice (21%), compression (32%) and elevation (58%) similarly between injury types. A complete RICE treatment was rarely applied (3%). Verbal...... information on RICE and rehabilitation was given in less than half of the cases. We conclude that the acute treatment of ankle sprains and muscle contusions in the Danish emergency rooms is not applied in accordance with consensus from international literature, and that the instruction in rehabilitation...

Prophylactic antidepressant treatment following acute coronary syndrome

DEFF Research Database (Denmark)

Christiansen, Ole G; Madsen, Michael T; Simonsen, Erik

2017-01-01

Major depressive disorder is significantly increased in patients following acute coronary syndrome resulting in twofold increased mortality compared with patients without depression. The depression diagnosis is often missed leading to considerable undertreatment. This systematic review assesses...... the current evidence of primary prophylactic treatment of depression in patients after acute coronary syndrome. The study protocol was prospectively registered at PROSPERO (registration number CRD42015025587). A systematic review were conducted and reported according to Preferred Reporting Items...... for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Embase, PsychINFO, CINAHL, and Cochran Library was searched. Two independent reviewers screened the records. The inclusion criteria were randomized controlled trials on adult patients with acute coronary syndrome treated prophylactically...

Adult Acute Lymphoblastic Leukemia Treatment (PDQ®)—Patient Version

Science.gov (United States)

Adult acute lymphoblastic leukemia (ALL; also called acute lymphocytic leukemia) is a blood cancer that often gets worse quickly if it is not treated. Treatments include chemotherapy, radiation therapy, stem cell transplant, and targeted therapy. Get detailed information about ALL in this expert-reviewed summary.

Clinical efficacy of ampicillin in treatment of acute odontogenic abscess

Directory of Open Access Journals (Sweden)

Matijević Stevo

2009-01-01

Full Text Available Background/Aim. Antibiotics choice and the duration of their application in the therapy of acute odontogenic abscess is considered to be controversial. The aim of this study was to investigate the clinical efficacy of ampicillin in treatment of acute odontogenic abscess and to assess the antimicrobial susceptibility of the isolated bacteria in early phase of abscess development. Methods. This study included 60 patients with acute odontogenic abscess who were surgically treated (extraction of teeth and/or abscess incision divided into two groups, ampicillin group and surgical group (without antibiotic treatment. Results. In the ampicillin group of patients treatment lasted on the average 4.67 days, while in the surgical group 6.17 days. A total of 78 bacterial strains were isolated from 60 patients. The most often bacteria were found to be Gram-positive facultative anaerobs (68/78. The most common bacteria isolated were Viridans streptococci (43/78. Susceptibility of isolated bacteria to ampicillin were 70.5%. Conclusion. Peroral use of ampicillin, after surgical treatment in an early phase of dentoalveolar abscess development, statistically significantly reduced the time of clinical symptoms of acute odontogenic abscess in comparison to surgical treatment only. The isolated bacterial strains in an early phase of dentoalveolar abscess development showed a high sensitivity to ampicillin.

Advances in individual prediction of methotrexate toxicity: a review

DEFF Research Database (Denmark)

Schmiegelow, K.

2009-01-01

pathways. In the coming years pharmacogenomics is expected to change our approaches to individualised therapy with methotrexate. However, genetic polymorphisms affect the pharmacokinetics and dynamics of all the drugs a patient receive as well as the normal tissues tolerance to a given drug exposure. Thus...

Synthesis and Evaluation of Hydrogen Peroxide Sensitive Prodrugs of Methotrexate and Aminopterin for the Treatment of Rheumatoid Arthritis

DEFF Research Database (Denmark)

Peiró Cadahía, Jorge; Bondebjerg, Jon; Hansen, Christian A.

2018-01-01

A series of novel hydrogen peroxide sensitive prodrugs of methotrexate (MTX) and aminopterin (AMT) were synthesized and evaluated for therapeutic efficacy in mice with collagen induced arthritis (CIA) as a model of chronic rheumatoid arthritis (RA). The prodrug strategy selected is based on ROS...... assays. Selected candidates showed moderate to good solubility, high chemical and enzymatic stability, and therapeutic efficacy comparable to the parent drugs in the CIA model. Importantly, the prodrugs displayed the expected safer toxicity profile and increased therapeutic window compared to MTX and AMT...

Treatment of acute diarrhea with Saccharomyces boulardii in infants.

Science.gov (United States)

Corrêa, Naflesia B O; Penna, Francisco J; Lima, Fátima M L S; Nicoli, Jacques R; Filho, Luciano A P

2011-11-01

The aim of the study was to determine whether an oral treatment with a commercial pharmaceutical product containing Saccharomyces boulardii would reduce the duration of diarrhea in infants with acute diarrhea. In the present double-blind, placebo-controlled study, 186 infants, 6 to 48 months old and hospitalized within 72 hours after the onset of acute diarrhea in 2 hospitals in Goiânia, Goiás, Brazil, were randomly assigned to receive twice per day for 5 days 200 mg of a commercial pharmaceutical product containing 4 × 10 viable cells of S boulardii or a placebo. Stool samples were submitted to search for rotavirus. Among the 176 infants who completed the trial, those treated with S boulardii (90) showed a reduction in diarrhea duration (P boulardii was given to children within 72 hours after the onset of acute diarrhea. The present study suggests a complementary treatment of acute diarrhea in infants with daily oral doses of S boulardii.

Multinational evidence-based recommendations for the use of methotrexate in rheumatic disorders with a focus on rheumatoid arthritis

DEFF Research Database (Denmark)

Visser, K; Katchamart, W; Loza, E

2009-01-01

the work-up before initiating methotrexate, optimal dosage and route, use of folic acid, monitoring, management of hepatotoxicity, long-term safety, mono versus combination therapy and management in the perioperative period and before/during pregnancy. One recommendation concerned methotrexate as a steroid...

Anti-infection treatment of iatrogenic acute radiation sickness

International Nuclear Information System (INIS)

Zhang Shulan; Ke Xiaoyan; Jia Tengzhen

2006-01-01

Objective: To occumulatle experience of anti-infection treatment in acute radiation sickness (ARS) induced by medical treatment in order to provide beneficial help for victims of accidental of acute radiation sickness. Methods: The changes of peripheral blood indices, body temperature and clinical symptoms of 17 cases who were clinically irradiated with 6.0-7.2 Gy X-rays were observed both before peripheral blood stem cell transplantation(PBSCT) and after anti-infection treatment. Results: WBC count began to decrease to below 1 x 10 9 /L from the 8th to 10th days after irradiation and maintained at row level for 4 days or for 13.3 days if the patients had not received rhG-CSF treatment. In 29.4% of patients the body temperature was higher than 38.5 degree C. After comprehensive enviromental protection and anti-infection treatment, all patients could successfully tide over the period of bone marrow depression without appearance of the typical critical phase of ARS. Conclusion: PBSCT and rhG-CSF treatment can reduce the time span for reconstruction of bone marrow. Comprehensive enviromental protection and combined anti-infection treatment are key points fm successful treatment. (authors)

Outpatient endometrial aspiration: an alternative to methotrexate for pregnancy of unknown location.

Science.gov (United States)

Insogna, Iris G; Farland, Leslie V; Missmer, Stacey A; Ginsburg, Elizabeth S; Brady, Paula C

2017-08-01

Pregnancies of unknown location with abnormal beta-human chorionic gonadotropin trends are frequently treated as presumed ectopic pregnancies with methotrexate. Preliminary data suggest that outpatient endometrial aspiration may be an effective tool to diagnose pregnancy location, while also sparing women exposure to methotrexate. The purpose of this study was to evaluate the utility of an endometrial sampling protocol for the diagnosis of pregnancies of unknown location after in vitro fertilization. A retrospective cohort study of 14,505 autologous fresh and frozen in vitro fertilization cycles from October 2007 to September 2015 was performed; 110 patients were diagnosed with pregnancy of unknown location, defined as a positive beta-human chorionic gonadotropin without ultrasound evidence of intrauterine or ectopic pregnancy and an abnormal beta-human chorionic gonadotropin trend (location, failed intrauterine pregnancy was diagnosed in 46 patients (42%), and ectopic pregnancy was diagnosed in 64 patients (58%). Clinical variables that included fresh or frozen embryo transfer, day of embryo transfer, serum beta-human chorionic gonadotropin at the time of sampling, endometrial thickness, and presence of an adnexal mass were not significantly different between patients with failed intrauterine pregnancy or ectopic pregnancy. In patients with failed intrauterine pregnancy, 100% demonstrated adequate postsampling beta-human chorionic gonadotropin declines; villi were identified in just 46% (n=21 patients). Patients with failed intrauterine pregnancy had significantly shorter time to resolution (negative serum beta-human chorionic gonadotropin) after sampling compared with patients with ectopic pregnancy (12.6 vs 26.3 days; Plocation are spared methotrexate, with a shorter time to pregnancy resolution than those who receive methotrexate. Copyright © 2017 Elsevier Inc. All rights reserved.

St. John's wort significantly increased the systemic exposure and toxicity of methotrexate in rats

International Nuclear Information System (INIS)

Yang, Shih-Ying; Juang, Shin-Hun; Tsai, Shang-Yuan; Chao, Pei-Dawn Lee; Hou, Yu-Chi

2012-01-01

St. John's wort (SJW, Hypericum perforatum) is one of the popular nutraceuticals for treating depression. Methotrexate (MTX) is an immunosuppressant with narrow therapeutic window. This study investigated the effect of SJW on MTX pharmacokinetics in rats. Rats were orally given MTX alone and coadministered with 300 and 150 mg/kg of SJW, and 25 mg/kg of diclofenac, respectively. Blood was withdrawn at specific time points and serum MTX concentrations were assayed by a specific monoclonal fluorescence polarization immunoassay method. The results showed that 300 mg/kg of SJW significantly increased the AUC 0−t and C max of MTX by 163% and 60%, respectively, and 150 mg/kg of SJW significantly increased the AUC 0−t of MTX by 55%. In addition, diclofenac enhanced the C max of MTX by 110%. The mortality of rats treated with SJW was higher than that of controls. In conclusion, coadministration of SJW significantly increased the systemic exposure and toxicity of MTX. The combined use of MTX with SJW would need to be with caution. -- Highlights: ► St. John's wort significantly increased the AUC 0−t and C max of methotrexate. ► Coadministration of St. John's wort increased the exposure and toxicity of methotrexate. ► The combined use of methotrexate with St. John's wort will need to be with caution.

Encapsulation of methotrexate loaded magnetic microcapsules for magnetic drug targeting and controlled drug release

Energy Technology Data Exchange (ETDEWEB)

Chakkarapani, Prabu [Department of Pharmaceutical Technology & Centre for Excellence in Nanobio Translational Research, Anna University, Bharathidasan Institute of Technology Campus, Tiruchirappalli 620024, Tamil Nadu (India); Subbiah, Latha, E-mail: lathasuba2010@gmail.com [Department of Pharmaceutical Technology & Centre for Excellence in Nanobio Translational Research, Anna University, Bharathidasan Institute of Technology Campus, Tiruchirappalli 620024, Tamil Nadu (India); Palanisamy, Selvamani; Bibiana, Arputha [Department of Pharmaceutical Technology & Centre for Excellence in Nanobio Translational Research, Anna University, Bharathidasan Institute of Technology Campus, Tiruchirappalli 620024, Tamil Nadu (India); Ahrentorp, Fredrik; Jonasson, Christian; Johansson, Christer [Acreo Swedish ICT AB, Arvid Hedvalls backe 4, SE-411 33 Göteborg (Sweden)

2015-04-15

We report on the development and evaluation of methotrexate magnetic microcapsules (MMC) for targeted rheumatoid arthritis therapy. Methotrexate was loaded into CaCO{sub 3}-PSS (poly (sodium 4-styrenesulfonate)) doped microparticles that were coated successively with poly (allylamine hydrochloride) and poly (sodium 4-styrenesulfonate) by layer-by-layer technique. Ferrofluid was incorporated between the polyelectrolyte layers. CaCO{sub 3}-PSS core was etched by incubation with EDTA yielding spherical MMC. The MMC were evaluated for various physicochemical, pharmaceutical parameters and magnetic properties. Surface morphology, crystallinity, particle size, zeta potential, encapsulation efficiency, loading capacity, drug release pattern, release kinetics and AC susceptibility studies revealed spherical particles of ~3 µm size were obtained with a net zeta potential of +24.5 mV, 56% encapsulation and 18.6% drug loading capacity, 96% of cumulative drug release obeyed Hixson-Crowell model release kinetics. Drug excipient interaction, surface area, thermal and storage stability studies for the prepared MMC was also evaluated. The developed MMC offer a promising mode of targeted and sustained release drug delivery for rheumatoid arthritis therapy. - Highlights: • Development of methotrexate magnetic microcapsules (MMC) by layer-by-layer method. • Characterization of physicochemical, pharmaceutical and magnetic properties of MMC. • Multiple layers of alternative polyelectrolytes prolongs methotrexate release time. • MMC is capable for targeted and sustained release rheumatoid arthritis therapy.

Mechanisms and Implications of Dual-Acting Methotrexate in Folate-Targeted Nanotherapeutic Delivery

Directory of Open Access Journals (Sweden)

Pamela T. Wong

2015-01-01

Full Text Available The rational design of a nanoplatform in drug delivery plays a crucial role in determining its targeting specificity and efficacy in vivo. A conventional approach relies on the surface conjugation of a nanometer-sized particle with two functionally distinct types of molecules, one as a targeting ligand, and the other as a therapeutic agent to be delivered to the diseased cell. However, an alternative simplified approach can be used, in which a single type of molecule displaying dual function as both a targeting ligand and therapeutic agent is conjugated to the nanoparticle. In this review, we evaluate the validity of this new strategy by using methotrexate, which displays multifunctional mechanisms of action. Methotrexate binds to the folate receptor, a surface biomarker frequently overexpressed in tumor cells, and also inhibits dihydrofolate reductase, an enzyme critical for cell survival and division. Thus we describe a series of fifth generation poly(amido amine dendrimers conjugated with methotrexate, and discuss several lines of evidence supporting the efficacy of this new platform strategy based on surface plasmon resonance spectroscopy, enzyme activity assays, and cell-based studies with folate receptor (+ KB cancer cells.

Treatment-related mortality in relapsed childhood acute lymphoblastic leukemia

DEFF Research Database (Denmark)

Oskarsson, Trausti; Söderhäll, Stefan; Arvidson, Johan

2018-01-01

BACKGROUND: Treatment of relapsed childhood acute lymphoblastic leukemia (ALL) is particularly challenging due to the high treatment intensity needed to induce and sustain a second remission. To improve results, it is important to understand how treatment-related toxicity impacts survival...

Emergency Treatment of Acute Asthma

OpenAIRE

Maxwell, David M.

1986-01-01

In assessing acute asthma, the physician must seek specific historical features, symptoms and physical findings. Recent work has shown, however, that while these features are associated with severity, their absence does not imply benignity. Objective measures of pulmonary function are required for accurate assessment of severity. A sequential treatment regimen using nebulized bronchodilators, vigorous rehydration, aminophylline, and corticosteroids should be employed. Status asthmaticus may r...

Biochemical criteria of toxicity of therapy with high doses of methotrexate in children with osteosarcoma

Directory of Open Access Journals (Sweden)

A. M. Strizhevskaya

2015-01-01

Full Text Available Methotrexate (Mtx is a cytotoxic drug from the group of antimetabolites, folic acid antagonists. High-dose (HD Mtx in pediatric oncology are used for the treatment of osteosarcoma (OS, and other types of tumors. This therapy has allowed to achieve a five-year relapse-free survival rates up to 80 % in patients with OS. However, the high toxicity of Mtx is a serious constraint in achieving the maximum therapeutic effect, which in most cases poses the occurrence of side effects in patients on various organs and systems. Treatment should be under strict laboratory monitoring, primarily therapeutic drug monitoring the concentration of Mtx in serum.246 children (boys – 125, girls – 121 aged 5 to 16 years with osteosarcoma (mean age 12.2 years who were treated in N.N. Blokhin Russian Cancer Research Center from 2006 to 2013. Patients were conducted from 1 to 8 courses HD Mtx at a dose of 8 or 12 g/m2 , administered within 4 h of infusion on the background of alkaline prehydrate. Leucovorin was administered intravenously, every 6 hours, starting 24 h from the start of the Mtx infusion. 1137 courses of HD Mtx were conducted with FPIA method (analyzer TDx/Flx, Abbott, USA. The technique of monitoring of homocysteine (Hcy in the blood serum by analyzer Vitros 5/1FS (Johnson & Johnson, USA during the entire course of high-dose Mtx was tested. In groups calculated pharmacokinetic parameters Mtx were tested: area under the pharmacokinetic curve (MtxAUC, clearance of methotrexate (ClMtx, the elimination half-life (T1/2 and the total time of excretion (Ttotal. Normal excretion of Mtx was revealed at 1050 courses Mtx, corresponding to the following values: 4 h – 1109 ± 283 μmol/l; 24 h – 4,67 ± 0,95 μmol/l; 42 h – 0,38 ± 0.16 µmol/l; 48 h – less than 0,23 ± 0.04 µmol/l; 72 h of 0.07 ± 0,03 µmol/l; 96 h of 0.03 ± 0.01 µmol/l. At 87 courses identified delayed Mtx excretion, accounting for 7.6 % of all courses. In all measured parameters

Esophageal strictures during treatment for acute lymphoblastic leukemia.

LENUS (Irish Health Repository)

Kelly, Kevin

2012-02-01

Esophageal stricture is a rare complication of paediatric cancer treatment that usually occurs after esophageal exposure to radiotherapy. We describe 4 cases of esophageal stricture during chemotherapy for acute lymphoblastic leukemia. All patients presented with refractory vomiting and were diagnosed with radiologic contrast studies. None of the patients had received radiotherapy. Esophageal candidiasis was seen in 2 patients but the remaining 2 patients had earlier systemic candidiasis. High-dose dexamethasone may predispose these children to both esophageal candidiasis and peptic esophagitis. The etiology of esophageal strictures during treatment for acute leukemia is likely to be multifactorial but systemic candidiasis may play a significant role.

Treatment for acute anterior cruciate ligament tear

DEFF Research Database (Denmark)

Frobell, Richard B; Roos, Harald P; Roos, Ewa M

2015-01-01

STUDY QUESTION: In young active adults with an acute anterior cruciate ligament (ACL) rupture, do patient reported or radiographic outcomes after five years differ between those treated with rehabilitation plus early ACL reconstruction and those treated with rehabilitation and optional delayed AC...... AND WHAT THIS PAPER ADDS: The relative efficacy of surgical reconstruction and rehabilitation for short and long term outcomes of ACL rupture is debated. Clinicians and young active adult patients should consider rehabilitation as a primary treatment option following an acute ACL tear....

Acute toxicity profile in prostate cancer with conventional and hypofractionated treatment

International Nuclear Information System (INIS)

Viani, Gustavo Arruda; Zulliani, Giseli Correa; Stefano, Eduardo Jose; Silva, Lucas Bernardes Godoy da; Silva, Bruna Bueno da; Crempe, Yuri Bonicelli; Martins, Vinicius Spazzapan; Ferrari, Ricardo Jose Rambaiolo; Pólo, Mariana Colbachini; Rossi, Bruno Thiago; Suguikawa, Elton

2013-01-01

To compare the acute toxicities in radical treatment of prostate cancer between conventional schedule (C-ARM) with 78 Gy/39 fractions and hypofractionation conformal treatment (H-ARM) with 69 Gy/23 fractions. This prospective double arm study consisted of 217 patients with prostate cancer, 112 in H-ARM and 105 in C-ARM arm. C-ARM received conventional six- field conformal radiotherapy with 78 Gy in 39 fractions while H-ARM received hypofractionation with 69 Gy in 23 fractions. Weekly assessment of acute reactions was done during treatment and with one, and 3 months using RTOG scale. Univariated analysis was performed to evaluate differences between the incidences of acute reaction in the treatment arms. Variables with p value less than 0.1 were included in the multivariated logistic regression. There was no difference between H-ARM versus C-ARM for severity and incidence in genitourinary (GU) and gastrointestinal (GI) acute toxicity. During the treatment comparing H-ARM with C-ARM no differences was observed for GI toxicity (grade 0–3; H-ARM = 45.5%, 34%, 18.7% and 1.8% versus C-ARM = 47.6%, 35.2%, 17.2% and 0). For acute GU toxicity no difference was detected between H-ARM (grade 0–3; 22.3%, 54.5%, 18.7% and 4.5%) and C-ARM (grade 0–3; 25.8%, 53.3%, 17.1% and 3.8%). At the 3- months follow-up, persistent Grade > =2 acute GU and GI toxicity were 2.5% and 1.8% in H-ARM versus 5.7% and 3% in C-ARM (p > 0.05). In univariated and multivariated analyses, there was not any dosimetric predictor for GI and GU toxicity. Our data demonstrate that hypofractionated radiotherapy achieving high biological effective dose using conformal radiotherapy is feasible for prostate cancer, being well tolerated with minimal severe acute toxicity

Appropriate treatment of acute sigmoid volvulus in the emergency setting

Science.gov (United States)

Lou, Zheng; Yu, En-Da; Zhang, Wei; Meng, Rong-Gui; Hao, Li-Qiang; Fu, Chuan-Gang

2013-01-01

AIM: To investigate an appropriate strategy for the treatment of patients with acute sigmoid volvulus in the emergency setting. METHODS: A retrospective review of 28 patients with acute sigmoid volvulus treated in the Department of Colorectal Surgery, Changhai Hospital, Shanghai from January 2001 to July 2012 was performed. Following the diagnosis of acute sigmoid volvulus, an initial colonoscopic approach was adopted if there was no evidence of diffuse peritonitis. RESULTS: Of the 28 patients with acute sigmoid volvulus, 19 (67.9%) were male and 9 (32.1%) were female. Their mean age was 63.1 ± 22.9 years (range, 21-93 years). Six (21.4%) patients had a history of abdominal surgery, and 17 (60.7%) patients had a history of constipation. Abdominal radiography or computed tomography was performed in all patients. Colonoscopic detorsion was performed in all 28 patients with a success rate of 92.8% (26/28). Emergency surgery was required in the other two patients. Of the 26 successfully treated patients, seven (26.9%) had recurrent volvulus. CONCLUSION: Colonoscopy is the primary emergency treatment of choice in uncomplicated acute sigmoid volvulus. Emergency surgery is only for patients in whom nonoperative treatment is unsuccessful, or in those with peritonitis. PMID:23946604

Outcome following late marrow relapse in childhood acute lymphoblastic leukemia

International Nuclear Information System (INIS)

Chessells, J.; Leiper, A.; Rogers, D.

1984-01-01

Thirty-four children with acute lymphoblastic leukemia, who developed bone marrow relapse after treatment was electively stopped, received reinduction, consolidation, continuing therapy, and intrathecal (IT) methotrexate (MTX). Sixteen children who relapsed within six months of stopping treatment had a median second-remission duration of 26 weeks; all next relapses occurred in the bone marrow. In 18 children who relapsed later, the median duration of second remission was in excess of two years, but after a minimum of four years follow-up, 16 patients have so far relapsed again (six in the CNS). CNS relapse occurred as a next event in four of 17 children who received five IT MTX injections only and in two of 14 children who received additional regular IT MTX. Although children with late marrow relapses may achieve long second remissions, their long-term out-look is poor, and regular IT MTX does not afford adequate CNS prophylaxis. It remains to be seen whether more intensive chemotherapy, including high-dose chemoradiotherapy and bone marrow transplantation, will improve the prognosis in this group of patients

Re-evaluating the treatment of acute optic neuritis.

Science.gov (United States)

Bennett, Jeffrey L; Nickerson, Molly; Costello, Fiona; Sergott, Robert C; Calkwood, Jonathan C; Galetta, Steven L; Balcer, Laura J; Markowitz, Clyde E; Vartanian, Timothy; Morrow, Mark; Moster, Mark L; Taylor, Andrew W; Pace, Thaddeus W W; Frohman, Teresa; Frohman, Elliot M

2015-07-01

Clinical case reports and prospective trials have demonstrated a reproducible benefit of hypothalamic-pituitary-adrenal (HPA) axis modulation on the rate of recovery from acute inflammatory central nervous system (CNS) demyelination. As a result, corticosteroid preparations and adrenocorticotrophic hormones are the current mainstays of therapy for the treatment of acute optic neuritis (AON) and acute demyelination in multiple sclerosis.Despite facilitating the pace of recovery, HPA axis modulation and corticosteroids have failed to demonstrate long-term benefit on functional recovery. After AON, patients frequently report visual problems, motion perception difficulties and abnormal depth perception despite 'normal' (20/20) vision. In light of this disparity, the efficacy of these and other therapies for acute demyelination require re-evaluation using modern, high-precision paraclinical tools capable of monitoring tissue injury.In no arena is this more amenable than AON, where a new array of tools in retinal imaging and electrophysiology has advanced our ability to measure the anatomic and functional consequences of optic nerve injury. As a result, AON provides a unique clinical model for evaluating the treatment response of the derivative elements of acute inflammatory CNS injury: demyelination, axonal injury and neuronal degeneration.In this article, we examine current thinking on the mechanisms of immune injury in AON, discuss novel technologies for the assessment of optic nerve structure and function, and assess current and future treatment modalities. The primary aim is to develop a framework for rigorously evaluating interventions in AON and to assess their ability to preserve tissue architecture, re-establish normal physiology and restore optimal neurological function. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Methotrexate loaded polyether-copolyester dendrimers for the treatment of gliomas: enhanced efficacy and intratumoral transport capability.

Science.gov (United States)

Dhanikula, Renu Singh; Argaw, Anteneh; Bouchard, Jean-Francois; Hildgen, Patrice

2008-01-01

Therapeutic benefit in glial tumors is often limited due to low permeability of delivery systems across the blood-brain barrier (BBB), drug resistance, and poor penetration into the tumor tissue. In an attempt to overcome these hurdles, polyether-copolyester (PEPE) dendrimers were evaluated as drug carriers for the treatment of gliomas. Dendrimers were conjugated to d-glucosamine as the ligand for enhancing BBB permeability and tumor targeting. The efficacy of methotrexate (MTX)-loaded dendrimers was established against U87 MG and U 343 MGa cells. Permeability of rhodamine-labeled dendrimers and MTX-loaded dendrimers across the in vitro BBB model and their distribution into avascular human glioma tumor spheroids was also studied. Glucosylated dendrimers were found to be endocytosed in significantly higher amounts than nonglucosylated dendrimers by both the cell lines. IC 50 of MTX after loading in dendrimers was lower than that of the free MTX, suggesting that loading MTX in PEPE dendrimers increased its potency. Similar higher activity of MTX-loaded glucosylated and nonglucosylated dendrimers was found in the reduction of tumor spheroid size. These MTX-loaded dendrimers were able to kill even MTX-resistant cells highlighting their ability to overcome MTX resistance. In addition, the amount of MTX-transported across BBB was three to five times more after loading in the dendrimers. Glucosylation further increased the cumulative permeation of dendrimers across BBB and hence increased the amount of MTX available across it. Glucosylated dendrimers distributed through out the avascular tumor spheroids within 6 h, while nonglucosylated dendrimers could do so in 12 h. The results show that glucosamine can be used as an effective ligand not only for targeting glial tumors but also for enhanced permeability across BBB. Thus, glucosylated PEPE dendrimers can serve as potential delivery system for the treatment of gliomas.

Usability testing of ANSWER: a web-based methotrexate decision aid for patients with rheumatoid arthritis.

Science.gov (United States)

Li, Linda C; Adam, Paul M; Townsend, Anne F; Lacaille, Diane; Yousefi, Charlene; Stacey, Dawn; Gromala, Diane; Shaw, Chris D; Tugwell, Peter; Backman, Catherine L

2013-12-01

Decision aids are evidence-based tools designed to inform people of the potential benefit and harm of treatment options, clarify their preferences and provide a shared decision-making structure for discussion at a clinic visit. For patients with rheumatoid arthritis (RA) who are considering methotrexate, we have developed a web-based patient decision aid called the ANSWER (Animated, Self-serve, Web-based Research Tool). This study aimed to: 1) assess the usability of the ANSWER prototype; 2) identify strengths and limitations of the ANSWER from the patient's perspective. The ANSWER prototype consisted of: 1) six animated patient stories and narrated information on the evidence of methotrexate for RA; 2) interactive questionnaires to clarify patients' treatment preferences. Eligible participants for the usability test were patients with RA who had been prescribed methotrexate. They were asked to verbalize their thoughts (i.e., think aloud) while using the ANSWER, and to complete the System Usability Scale (SUS) to assess overall usability (range = 0-100; higher = more user friendly). Participants were audiotaped and observed, and field notes were taken. The testing continued until no new modifiable issues were found. We used descriptive statistics to summarize participant characteristics and the SUS scores. Content analysis was used to identified usability issues and navigation problems. 15 patients participated in the usability testing. The majority were aged 50 or over and were university/college graduates (n = 8, 53.4%). On average they took 56 minutes (SD = 34.8) to complete the tool. The mean SUS score was 81.2 (SD = 13.5). Content analysis of audiotapes and field notes revealed four categories of modifiable usability issues: 1) information delivery (i.e., clarity of the information and presentation style); 2) navigation control (i.e., difficulties in recognizing and using the navigation control buttons); 3) layout (i.e., position of the

Cerebral venous and sinus thrombosis with cerebrospinal fluid circulation block after the first methotrexate administration by lumbar puncture

International Nuclear Information System (INIS)

Bienfait, H.P.; Gijtenbeek, J.M.M.; Bent, M.J. van; Bruin, H.G. de; Voogt, P.J.; Pillay, M.

2002-01-01

We report a patient treated for small lymphocytic lymphoma/leukemia with cerebral venous and sinus thrombosis (CVST) after lumbar puncture with intrathecal administration of methotrexate (MTX). He also developed a cerebrospinal fluid flow block. This is the first report of an association between lumbar puncture and intrathecally administered MTX and the development of CVST. Intrathecal treatment in this patient was discontinued and he was successfully treated with high-dose low-molecular-weight heparin subcutaneously. (orig.)

Adult Acute Myeloid Leukemia Treatment (PDQ®)—Patient Version

Science.gov (United States)

Treatment options for adult acute myeloid leukemia (AML) include chemotherapy, radiation therapy, stem cell transplant, and other medications. Get detailed information about the treatment of new and recurrent AML in this expert-reviewed summary.

A qualitative analysis of methotrexate self-injection education videos on YouTube.

Science.gov (United States)

Rittberg, Rebekah; Dissanayake, Tharindri; Katz, Steven J

2016-05-01

The aim of this study is to identify and evaluate the quality of videos for patients available on YouTube for learning to self-administer subcutaneous methotrexate. Using the search term "Methotrexate injection," two clinical reviewers analyzed the first 60 videos on YouTube. Source and search rank of video, audience interaction, video duration, and time since video was uploaded on YouTube were recorded. Videos were classified as useful, misleading, or a personal patient view. Videos were rated for reliability, comprehensiveness, and global quality scale (GQS). Reasons for misleading videos were documented, and patient videos were documented as being either positive or negative towards methotrexate (MTX) injection. Fifty-one English videos overlapped between the two geographic locations; 10 videos were classified as useful (19.6 %), 14 misleading (27.5 %), and 27 personal patient view (52.9 %). Total views of videos were 161,028: 19.2 % useful, 72.8 % patient, and 8.0 % misleading. Mean GQS: 4.2 (±1.0) useful, 1.6 (±1.1) misleading, and 2.0 (±0.9) for patient videos (p tool available, clinicians need to be familiar with specific resources to help guide and educate their patients to ensure best outcomes.

The Circadian Schedule for Childhood Acute Lymphoblastic Leukemia Maintenance Therapy does not Influence Event-Free Survival in the NOPHO ALL92 Protocol

DEFF Research Database (Denmark)

Clemmensen, Kim K. B.; Christensen, Regitse H.; Shabaneh, Diana N.

2014-01-01

BACKGROUND: The event-free survival of childhood acute lymphoblastic leukemia (ALL) has been reported to be superior when oral methotrexate (MTX) and 6-mercaptopurine (6MP) maintenance therapy (MT) is administered in the evening compared to the morning. PROCEDURE: In the ALL92 MT study we prospec...

Reduced cerebral glucose metabolism and increased brain capillary permeability following high-dose methotrexate chemotherapy: a positron emission tomographic study

International Nuclear Information System (INIS)

Phillips, P.C.; Dhawan, V.; Strother, S.C.; Sidtis, J.J.; Evans, A.C.; Allen, J.C.; Rottenberg, D.A.

1987-01-01

Regional glucose metabolic rate constants and blood-to-brain transport of rubidium were estimated using positron emission tomography in an adolescent patient with a brain tumor, before and after chemotherapy with intravenous high-dose methotrexate. Widespread depression of cerebral glucose metabolism was apparent 24 hours after drug administration, which may reflect reduced glucose phosphorylation, and the influx rate constant for 82 Rb was increased, indicating a drug-induced alteration in blood-brain barrier function. Associated changes in neuropsychological performance, electroencephalogram, and plasma amino acid concentration were identified in the absence of evidence of systemic methotrexate toxicity, suggesting primary methotrexate neurotoxicity

Outcomes after treatment of acute aortic occlusion.

Science.gov (United States)

de Varona Frolov, Serguei R; Acosta Silva, Marcela P; Volo Pérez, Guido; Fiuza Pérez, Maria D

2015-11-01

Acute aortic occlusion (AAO) is a rare disease with high morbidity and mortality. The aim of this study was to describe the results of surgical treatment of acute aortic occlusion and risk factors for mortality. Retrospective review of the clinical history of 29 patients diagnosed and operated on for AAO during 28 years. The following variables were analysed: age, sex, tabaco use, diabetes, chronic renal insufficiency, chronic heart failure, atrial fibrillation, arterial hypertension, symptoms, diagnosis and treatment, 30-day mortality and long-term survival. A univariant analysis was performed of variables related to mortality. Twenty-nine patients were included (18 male) with a mean age of 66,2 years. The aetiology was: embolism (EM) in 11 cases and Thrombosis (TR) in 18 cases. The surgical procedures performed included bilateral transfemoral thrombectomy (14 cases), aorto-bifemoral by-pass (8 cases), axilo uni/bifemoral by-pass (5 cases) and aortoiliac and renal tromboendarterectomy (2 cases). Morbidity included: renal failure (14 cases), mesenteric ischemia (4 cases), cardiac complications (7 cases), respiratory complications (5 cases) and loss of extremity (2 cases). The in-hospital mortality was 21% (EM 0%, TR 21%). The estimated survival at 1.3 and 5 years was 60, 50 and 44% respectively. Age (p=0.032), arterial hypertension (p=0.039) and aetiology of the AAO (p=0.039) were related to mortality. Acute aortic occlusion is a medical emergency with high mortality rates. Acute renal failure is the most common postoperative complication. Copyright © 2012 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

CT findings of children with acute leukemia with special reference to 5 cases of leukoencephalopathy

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Hattori, Haruo; Akiyama, Yuichi; Takao, Tatsuo; Ito, Masatoshi; Nakano, Shozo (Kyoto Univ. (Japan). Faculty of Medicine)

1983-10-01

CT scans of the brain were taken 122 times in 43 children with acute leukemia. CT evidence of cerebral atrophy was seen in 58.1% (25/43) of the children. Of the children who were studied during initial antileukemic therapy, such as remission-induction therapy and CNS prophylaxis, 67.7% (21/31) also had CT evidence of cerebral atrophy. This high incidence was considered mainly due to the administration of the glucocorticoid hormone during the remission-induction therapy. Leukoencephalopathy developed in 11.6% (5/43) of the children. These 5 cases had CNS leukemia, systemic or intrathecal methotrexate administration, or CNS irradiation; the common factor was intrathecal methotrexate administration. Low-density areas in the cerebral white matter, ventricular dilatation, and intracerebral calcification were found on CT. The distribution of these areas was symmetrical (periventricular lucency), asymmetrical, or focal. Only 2 of these 5 children had intracerebral calcification; they survived more than 5 years after the onset of acute leukemia. CT was useful in evaluating 2 other asymptomatic children with low-density areas in the cerebral white matter. This finding was suggestive of preclinical or subclinical leukoencephalopathy.

CT findings of children with acute leukemia with special reference to 5 cases of leukoencephalopathy

International Nuclear Information System (INIS)

Hattori, Haruo; Akiyama, Yuichi; Takao, Tatsuo; Ito, Masatoshi; Nakano, Shozo

1983-01-01

CT scans of the brain were taken 122 times in 43 children with acute leukemia. CT evidence of cerebral atrophy was seen in 58.1% (25/43) of the children. Of the children who were studied during initial antileukemic therapy, such as remission-induction therapy and CNS prophylaxis, 67.7% (21/31) also had CT evidence of cerebral atrophy. This high incidence was considered mainly due to the administration of the glucocorticoid hormone during the remission-induction therapy. Leukoencephalopathy developed in 11.6% (5/43) of the children. These 5 cases had CNS leukemia, systemic or intrathecal methotrexate administration, or CNS irradiation; the common factor was intrathecal methotrexate administration. Low-density areas in the cerebral white matter, ventricular dilatation, and intracerebral calcification were found on CT. The distribution of these areas was symmetrical (periventricular lucency), asymmetrical, or focal. Only 2 of these 5 children had intracerebral calcification; they survived more than 5 years after the onset of acute leukemia. CT was useful in evaluating 2 other asymptomatic children with low-density areas in the cerebral white matter. This finding was suggestive of preclinical or subclinical leukoencephalopathy. (author)

Successful Laparoscopically Assisted Transcervical Suction Evacuation of Interstitial Pregnancy following Failed Methotrexate Injection in a Community Hospital Setting

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Rani B. Fritz

2014-01-01

Full Text Available We report on a case of a patient with an early diagnosed cornual ectopic pregnancy following failed methotrexate treatment. The patient was subsequently taken to the operating room for a laparoscopic guided transcervical suction curettage of the cornual ectopic. The surgery was successful and the patient was followed up until her urine pregnancy test was negative. We conclude that in properly selected patients, cornual ectopic pregnancy may be treated with transcervical suction curettage.

Electron microscope studies of methotrexate and radiation effects in human squamous cell carcinoma of the mouth

International Nuclear Information System (INIS)

De Martino, C.

1974-01-01

Serial biopsy specimens from two squamous cell carcinomas of the mouth were studied by electron microscopy. This report described the ultrastructural changes in the cells produced by treatment with methotrexate followed by irradiation. The main ultrastructural findings after treatment are: numerous autophagic lysosomes and residual bodies are visible in the cytoplasm of the tumor cells; mitochondria are swollen. The mitochondrial cristae are distorted and disrupted, and mitochondrial matrix disappears; the nucleolus shows a series of morphological changes such as development of a compact nucleolus, aggregation of granular elements, atrophy, dissolution and fragmentation of the nucleolar mass; infiltration of lymphocytes, granulocytes and macrophages in the tumor. The significance of these ultrastructural findings is discussed. (U.S.)

Stability study of methotrexate in 0.9% sodium chloride injection and 5% dextrose injection with limit tests for impurities

DEFF Research Database (Denmark)

Nissen, Klaus; Bogedal Jorgensen, Lene; Lindegaard Berg, Dorthe

2017-01-01

Purpose. Results of an evaluation of the stability of methotrexate in 0.9% sodium chloride injection and 5% dextrose injection are presented. Methods. Methotrexate concentrated solution (100 mg/mL) was diluted to nominal concentrations of 0.2 and 20 mg/mL in infusion bags containing 0.9% sodium...... chloride injection or 5% dextrose injection. The filled bags were stored for 28 days at 25 °C and 60% relative humidity and protected from light. Samples were withdrawn for analysis on the day of preparation and after 3, 7, 14, 21, and 28 days. The test program included visual inspections, measurements...... in amounts of known and unknown degradation products were detected. In 5% dextrose injection, methotrexate at the higher concentration was stable for 28 days, with minor formation of degradation products; in the 0.2-mg/mL solution, however, methotrexate was stable for only 3 days. At later time points...

Ineffective acute treatment of episodic migraine is associated with new-onset chronic migraine.

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Lipton, Richard B; Fanning, Kristina M; Serrano, Daniel; Reed, Michael L; Cady, Roger; Buse, Dawn C

2015-02-17

To test the hypothesis that ineffective acute treatment of episodic migraine (EM) is associated with an increased risk for the subsequent onset of chronic migraine (CM). In the American Migraine Prevalence and Prevention Study, respondents with EM in 2006 who completed the Migraine Treatment Optimization Questionnaire (mTOQ-4) and provided outcome data in 2007 were eligible for analyses. The mTOQ-4 is a validated questionnaire that assesses treatment efficacy based on 4 aspects of response to acute treatment. Total mTOQ-4 scores were used to define categories of acute treatment response: very poor, poor, moderate, and maximum treatment efficacy. Logistic regression models were used to examine the dichotomous outcome of transition from EM in 2006 to CM in 2007 as a function of mTOQ-4 category, adjusting for covariates. Among 5,681 eligible study respondents with EM in 2006, 3.1% progressed to CM in 2007. Only 1.9% of the group with maximum treatment efficacy developed CM. Rates of new-onset CM increased in the moderate treatment efficacy (2.7%), poor treatment efficacy (4.4%), and very poor treatment efficacy (6.8%) groups. In the fully adjusted model, the very poor treatment efficacy group had a more than 2-fold increased risk of new-onset CM (odds ratio = 2.55, 95% confidence interval 1.42-4.61) compared to the maximum treatment efficacy group. Inadequate acute treatment efficacy was associated with an increased risk of new-onset CM over the course of 1 year. Improving acute treatment outcomes might prevent new-onset CM, although reverse causality cannot be excluded. © 2015 American Academy of Neurology.

Marrow transplantation for leukemia following fractionated total body irradiation. A comparative trial of methotrexate and cyclosporine

International Nuclear Information System (INIS)

Irle, C.; Deeg, H.J.; Buckner, C.D.; Swedish Hospital Medical Center, Seattle, WA; Veterans Administration Hospital, Seattle, WA; Washington Univ., Seattle

1985-01-01

Fifty-six patients, 30-47 yr of age, with leukemia in relapse received allogeneic marrow transplants from HLA-identical siblings. All patients were treated with cyclophosphamide (120 mg/kg) and 7 daily fractions of 2.25 Gy of total body irradiation (TBI) for seven consecutive days. Nine patients (16%) are currently alive, free of disease, 324-845 days from transplantation. Actuarial relapse and survival rates at 2 yr were 56% and 9.5% respectively. These data were not remarkably different from those in previous studies using 10 Gy of TBI administered as a single dose. Thirty patients were randomized to receive methotrexate (MTX) and 26 to receive cyclosporine (CSP) as postgrafting prophylaxis for acute graft-versus-host disease (GVHD). Probability of developing significant acute GVHD by day 100 post-transplant was 71% for patients in the MTX group and 45% for patients in the CSP group (p<0.05). Probability of relapse was 37% for patients in the MTX group and 70% for patients in the CSP group (p<0.05). Transplant-related deaths were more frequent in the MTX group and leukemic deaths more frequent in the CSP group although this may have been related to an uneven distribution of high-risk patients. Long term disease-free survival was comparable. (author)

Relationship of peak serum methotrexate concentration to prognosis and drug tolerance in non-metastatic extremity osteosarcomas.

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Wang, Bo; Yao, Hao; Xie, Xianbiao; Yin, Junqiang; Zou, Changye; Huang, Gang; Shen, Jingnan

2018-05-28

This study aimed to explore whether peak serum methotrexate concentration (C max ) correlated with adverse events, overall survival (OS) and event-free survival (EFS) in patients with primary extremity osteosarcoma. Patients with extremity osteosarcoma who were treated at our center between 2005 and 2015 were retrospectively studied. All the patients were Enneking stage II and had received standard perioperative chemotherapy composed of high-dose methotrexate, doxorubicin, cisplatin and ifosfamide. C max and treatment-associated toxicities of each cycle were recorded. OS and EFS were estimated and compared by Kaplan-Meier survival analysis, and Cox regression models were performed for univariate comparisons. In total, 567 patients were followed for an average of 53 months (24-104 months). The estimated 3- and 5-year EFS were 71.7 and 63.1%, and the 3- and 5-year OS were 78.2 and 72.9%, respectively. C max ranged from 527 to 2495 µmol/L with a mean value of 931 ± 106 µmol/L. No significant differences in EFS and OS (p = 0.18 and p = 0.28) were observed among patients with a mean C max  > 1500, > 1000, > 700 and  1500 µmol/L had significantly increased rates of grade 3-5 toxicity. In the univariate analysis, C max was not a prognostic factor for EFS (p = 0.08) or OS (p = 0.16). C max did not correlate significantly with the oncologic prognosis of non-metastatic extremity osteosarcoma patients treated by multi-agent chemotherapy; however, C max correlated closely with toxicities and complications. The persistent inclusion of methotrexate in classical multidisciplinary chemotherapy was questioned and should be examined in future trials.

Influence of polymorphisms within the methotrexate pathway genes on the toxicity and efficacy of methotrexate in patients with juvenile idiopathic arthritis.

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Yanagimachi, Masakatsu; Naruto, Takuya; Hara, Takuma; Kikuchi, Masako; Hara, Ryoki; Miyamae, Takako; Imagawa, Tomoyuki; Mori, Masaaki; Kaneko, Tetsuji; Morita, Satoshi; Goto, Hiroaki; Yokota, Shumpei

2011-02-01

We investigated whether several polymorphisms within the methotrexate (MTX) pathway genes were related to the toxicity and efficacy of MTX in 92 Japanese patients with articular-type juvenile idiopathic arthritis (JIA). Eight gene polymorphisms within the MTX pathway genes, namely, RFC, BCRP, MTHFR (two), FPGS, γ-glutamyl hydrolase (GGH; two) and ATIC, were genotyped using TaqMan assays. Liver dysfunction was defined as an increase in alanine transaminase to five times the normal upper limit. Non-responders to MTX were defined as patients refractory to MTX and were therefore treated with biologics. The non-TT genotype at GGH T16C was associated with a high risk of liver dysfunction (P=0.028, odds ratio=6.90, 95% confidence interval 1.38-34.5), even after adjustment for the duration of MTX treatment. A longer interval from disease onset to treatment (8.5 and 21.3 months, P=0.029) and rheumatoid factor positivity (P=0.026, odds ratio=2.87, 95% confidence interval 1.11-7.39) were associated with lower efficacy of MTX. The non-TT genotype at GGH T16C was associated with a high risk of liver dysfunction, presumably because the C allele of GGH C16T may reduce the activity of GGH. The time interval before MTX treatment and rheumatoid factor positivity were associated with the efficacy of MTX treatment. The pharmacogenetics of the MTX pathway genes affects the toxicity and efficacy of MTX in Japanese JIA patients. © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

Guidelines for the treatment of acute ischaemic stroke.

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Alonso de Leciñana, M; Egido, J A; Casado, I; Ribó, M; Dávalos, A; Masjuan, J; Caniego, J L; Martínez Vila, E; Díez Tejedor, E; Fuentes, B; Álvarez-Sabin, J; Arenillas, J; Calleja, S; Castellanos, M; Castillo, J; Díaz-Otero, F; López-Fernández, J C; Freijo, M; Gállego, J; García-Pastor, A; Gil-Núñez, A; Gilo, F; Irimia, P; Lago, A; Maestre, J; Martí-Fábregas, J; Martínez-Sánchez, P; Molina, C; Morales, A; Nombela, F; Purroy, F; Rodríguez-Yañez, M; Roquer, J; Rubio, F; Segura, T; Serena, J; Simal, P; Tejada, J; Vivancos, J

2014-03-01

Update of Acute Ischaemic Stroke Treatment Guidelines of the Spanish Neurological Society based on a critical review of the literature. Recommendations are made based on levels of evidence from published data and studies. Organized systems of care should be implemented to ensure access to the optimal management of all acute stroke patients in stroke units. Standard of care should include treatment of blood pressure (should only be treated if values are over 185/105 mmHg), treatment of hyperglycaemia over 155 mg/dl, and treatment of body temperature with antipyretic drugs if it rises above 37.5 °C. Neurological and systemic complications must be prevented and promptly treated. Decompressive hemicraniectomy should be considered in cases of malignant cerebral oedema. Intravenous thrombolysis with rtPA should be administered within 4.5 hours from symptom onset, except when there are contraindications. Intra-arterial pharmacological thrombolysis can be considered within 6 hours, and mechanical thrombectomy within 8 hours from onset, for anterior circulation strokes, while a wider window of opportunity up to 12-24 hours is feasible for posterior strokes. There is not enough evidence to recommend routine use of the so called neuroprotective drugs. Anticoagulation should be administered to patients with cerebral vein thrombosis. Rehabilitation should be started as early as possible. Treatment of acute ischaemic stroke includes management of patients in stroke units. Systemic thrombolysis should be considered within 4.5 hours from symptom onset. Intra-arterial approaches with a wider window of opportunity can be an option in certain cases. Protective and restorative therapies are being investigated. Copyright © 2011 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

Prediction of methotrexate intolerance in juvenile idiopathic arthritis: a prospective, observational cohort study.

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van Dijkhuizen, Evert Hendrik Pieter; Bulatović Ćalasan, Maja; Pluijm, Saskia M F; de Rotte, Maurits C F J; Vastert, Sebastiaan J; Kamphuis, Sylvia; de Jonge, Robert; Wulffraat, Nico M

2015-01-01

Methotrexate (MTX) is an effective and safe drug in the treatment of juvenile idiopathic arthritis (JIA). Despite its safety, MTX-related gastrointestinal adverse effects before and after MTX administration, termed MTX intolerance, occur frequently, leading to non-compliance and potentially premature MTX termination. The aim of this study was to construct a risk model to predict MTX intolerance. In a prospective JIA cohort, clinical variables and single nucleotide polymorphisms were determined at MTX start. The Methotrexate Intolerance Severity Score was employed to measure MTX intolerance in the first year of treatment. MTX intolerance was most prevalent at 6 or 12 months after MTX start, which was defined as the outcome for the prediction model. The model was developed in 152 patients using multivariable logistic regression analysis and subsequently internally validated using bootstrapping. The prediction model included the following predictors: JIA category, antinuclear antibody, parent/patient assessment of pain, Juvenile Arthritis Disease Activity Score-27, thrombocytes, alanine aminotransferase and creatinine. The model classified 77.5% of patients correctly, and 66.7% of patients after internal validation by bootstrapping. The lowest predicted risk of MTX intolerance was 18.9% and the highest predicted risk was 85.9%. The prediction model was transformed into a risk score (range 0-17). At a cut-off of ≥6, sensitivity was 82.0%, specificity 56.1%, positive predictive value was 58.7% and negative predictive value 80.4%. This clinical prediction model showed moderate predictive power to detect MTX intolerance. To develop into a clinically usable tool, it should be validated in an independent cohort and updated with new predictors. Such an easy-to-use tool could then assist clinicians in identifying patients at risk to develop MTX intolerance, and in turn to monitor them closely and intervene timely in order to prevent the development of MTX intolerance

Multicenter study of environmental contamination with cyclophosphamide, ifosfamide, and methotrexate in 48 Canadian hospitals.

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Poupeau, Céline; Tanguay, Cynthia; Caron, Nicolas J; Bussières, Jean-François

2018-01-01

Context Oncology workers are occupationally exposed to antineoplastic drugs. This exposure can induce adverse health effects. In order to reduce their exposure, contamination on surfaces should be kept as low as possible. Objectives To monitor environmental contamination with cyclophosphamide, ifosfamide, and methotrexate in oncology pharmacy and patient care areas in Canadian hospitals. To describe the impact of some factors that may limit contamination. Methods This is a descriptive study. Twelve standardized sites were sampled in each participating center (six in the pharmacy and six in patient care areas). Samples were analyzed for the presence of cyclophosphamide, ifosfamide, and methotrexate by ultra-performance liquid chromatography tandem mass spectrometry technology. Descriptive statistical analyses were done and results were compared with a Kolmogorov-Smirnov test for independent samples. Results In 2015, 48 hospitals participated in this study (48/202, 24%). Overall, 34% (181/525) of the samples were positive for cyclophosphamide, 8% (41/525) for ifosfamide, and 6% (31/525) for methotrexate. The 75th percentile value of cyclophosphamide surface concentration was 6.9 pg/cm 2 . For ifosfamide and methotrexate, they were lower than the limit of detection. Centers who prepared more antineoplastic drugs per year and centers who used more cyclophosphamide per year showed significantly higher surface contamination ( p contamination. Conclusion In comparison with other multicenter studies that were conducted in Canada, the concentration of antineoplastic drugs measured on surfaces is decreasing. Regular environmental monitoring is a good practice in order to maintain contamination as low as reasonably achievable.

Co-association of methotrexate and SPIONs into anti-CD64 antibody-conjugated PLGA nanoparticles for theranostic application.

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Moura, Catarina Costa; Segundo, Marcela A; Neves, José das; Reis, Salette; Sarmento, Bruno

2014-01-01

Rheumatoid arthritis (RA) is an autoimmune disease with severe consequences for the quality of life of sufferers. Regrettably, the inflammatory process involved remains unclear, and finding successful therapies as well as new means for its early diagnosis have proved to be daunting tasks. As macrophages are strongly associated with RA inflammation, effective diagnosis and therapy may encompass the ability to target these cells. In this work, a new approach for targeted therapy and imaging of RA was developed based on the use of multifunctional polymeric nanoparticles. Poly(lactic-co-glycolic acid) nanoparticles were prepared using a single emulsion-evaporation method and comprisaed the co-association of superparamagnetic iron oxide nanoparticles (SPIONs) and methotrexate. The nanoparticles were further functionalized with an antibody against the macrophage-specific receptor, CD64, which is overexpressed at sites of RA. The devised nanoparticles were characterized for mean particle size, polydispersity index, zeta potential, and morphology, as well as the association of SPIONs, methotrexate, and the anti-CD64 antibody. Lastly, the cytotoxicity of the developed nanoparticles was assessed in RAW 264.7 cells using standard MTT and LDH assays. The nanoparticles had a mean diameter in the range of 130-200 nm and zeta potential values ranging from -32 mV to -16 mV. Association with either methotrexate or SPIONs did not significantly affect the properties of the nanoparticles. Conjugation with the anti-CD64 antibody, in turn, caused a slight increase in size and surface charge. Transmission electron microscopy confirmed the association of SPIONs within the poly(lactic-co-glycolic acid) matrix. Both anti-CD64 and methotrexate association were confirmed by Fourier transform infrared spectroscopy, and quantified yielding values as high as 36% and 79%, respectively. In vitro toxicity studies confirmed the methotrexate-loaded nanosystem to be more effective than the free drug

Efficacy of royal jelly on methotrexate-induced systemic oxidative ...

African Journals Online (AJOL)

The aim of this present study is to investigate the mucositis caused by methotrexate (MTX), as well as whether the application of royal jelly (RJ) has a protective effect on oxidative stress. This present study included six groups each consisted of 12 Wistar rats. Distilled water (po: peroral) was given to the 1st group as placebo ...

[Fiessinger-Leroy-Reiter syndrome with non-obstructive cardiomyopathy treated with methotrexate].

Science.gov (United States)

Blétry, O; De Prost, Y; Scheuble, C; Frank, R; Godeau, P

1979-07-01

The case of a 50 year old male with the Fiessinger-Leroy-Reiter syndrome, ankylosing spondylitis and generalised pustular psoriasis is reported. This condition wax complicated by non-obstructive cardiomyopathy, congestive cardiac failure and first-degree atrioventricular block, the site of which was localised by electrophysiological studies (nodal block with an infrahisian conduction defect). After failure of several therapeutic regimes, a spectacular improvement was obtained with Methotrexate associated with a diuretic; the signs of heart failure regressed and the cardiomyopathy stablised. A parallel improvement was seen in the skin, cardiac and articular lesions and has been maintained with an 18 months follow-up. Left ventricular performance was studied by echocardiography. The mechanism of the beneficial effect of Methotrexate is unclear; this therapeutic trial is to be extended to include other cases of primary cardiomyopathy without obstruction.

Predictors of mental health-related acute service utilisation and treatment costs in the 12 months following an acute psychiatric admission.

Science.gov (United States)

Siskind, Dan; Harris, Meredith; Diminic, Sandra; Carstensen, Georgia; Robinson, Gail; Whiteford, Harvey

2014-11-01

A key step in informing mental health resource allocation is to identify the predictors of service utilisation and costs. This project aims to identify the predictors of mental health-related acute service utilisation and treatment costs in the year following an acute public psychiatric hospital admission. A dataset containing administrative and routinely measured outcome data for 1 year before and after an acute psychiatric admission for 1757 public mental health patients was analysed. Multivariate regression models were developed to identify patient- and treatment-related predictors of four measures of service utilisation or cost: (a) duration of index admission; and, in the year after discharge from the index admission (b) acute psychiatric inpatient bed-days; (c) emergency department (ED) presentations; and (d) total acute mental health service costs. Split-sample cross-validation was used. A diagnosis of psychosis, problems with living conditions and prior acute psychiatric inpatient bed-days predicted a longer duration of index admission, while prior ED presentations and self-harm predicted a shorter duration. A greater number of acute psychiatric inpatient bed-days in the year post-discharge were predicted by psychosis diagnosis, problems with living conditions and prior acute psychiatric inpatient admissions. The number of future ED presentations was predicted by past ED presentations. For total acute care costs, diagnosis of psychosis was the strongest predictor. Illness acuity and prior acute psychiatric inpatient admission also predicted higher costs, while self-harm predicted lower costs. The development of effective models for predicting acute mental health treatment costs using existing administrative data is an essential step towards a workable activity-based funding model for mental health. Future studies would benefit from the inclusion of a wider range of variables, including ethnicity, clinical complexity, cognition, mental health legal status

Methotrexate-Induced Accumulation of Fluorescent Annexin V in Collagen-Induced Arthritis

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Andreas Wunder

2005-01-01

Full Text Available We examined the accumulation of Cy5.5-labeled annexin V in the paws of mice with and without collagen-induced arthritis, with and without methotrexate (MTX treatment, by near-infrared fluorescence imaging. Fluorescence reflectance imaging (FRI of paws was performed 48 hr after MTX injection and at 10 min and 3 hr after the injection of Cy5.5-annexin V (1 nmol dye per mouse. With arthritic paws, MTX treatment caused a 7-fold increase in fluorescence intensity compared with the paws of untreated mice and a 4-fold increase compared to nonarthritic paws of MTX-treated mice (p < .001 each. Tissue samples of paws were examined histologically for Cy5.5 fluorescence and by TUNEL staining for apoptosis. Cy5.5-annexin V was seen in the hyperplastic synovia of MTX-treated mice, and TUNEL staining for apoptosis showed apoptotic cells in the hyperplastic synovia. Monitoring the uptake of Cy5.5-annexin V in arthritic paws by FRI provided a method of assessing a response to MTX, a response that was readily quantitated with simple instrumentation and that occurred before conventional measurements of treatment response.

Acute Clinically Mastitic Animals in villages of Assiut Governance: Diagnosis and Treatment

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Mohammad Sayed and Ahmed Abdel Rady

Full Text Available This investigation was run in some villages in Assiut governance during summer 2007 to diagnose acute clinical mastitis in different animal species and to apply different lines of treatment for evaluating which treatment line of choice giving cure, aiming to another goal by preventing the conversion of acute mastitis towards the chronic one which is difficult to be treated and the dairy animal will be excluded. Therefore, 2150 animals were clinically examined in 5 villages located north to Assiut city, Egypt, including 400 cows, 950 ewes and 800 she goats, and the incidence of acute clinical mastitis was 22.50%, 2.63% and 4.63%, respectively. Milk samples were collected from all clinically mastitic cows for bacteriological examination to identify the causative agents of the intra-mammary infection (IMI. It was found the major causative agents isolated were Staphylococcus aureus, Streptococcus agalactiae, Escherichia coli and Corynebacterium pyogenes, causing either single or mixed type of infection. When applying different lines of treatment, all diseased animals were classified into 3 groups: 1st group received local treatment by intra-mammary infusion antibiotic. 2nd group received systematic treatment by intra-muscular (I/M injection of both antibiotic and anti-inflammatory drugs. While, 3rd group received combination of both local and systematic treatment lines together. Cure% was achieved as 50% for 1st group, 90% for 2nd group, while 3rd group gave complete cure by 100%. It was noticed that the incidence of acute clinical mastitis among examined cows was worrisome and can be considered as indicator of the epidemiology of the disease. While, spreading of the disease among ewes and she goats was somewhat low in comparison with that of cows. In conclusion, combination of both local and systematic treatment lines together should be advised in treatment of acute clinical mastitis to ensure complete cure. The obtained results highlighted the

Effect of edaravone torasemide treatment on elderly patients with acute cerebral hemorrhage

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Jiao Jiao

2016-12-01

Full Text Available Objective: To observe the effect of edaravone torasemide treatment on acute cerebral hemorrhage in elderly patients. Methods: A total of 100 patient with acute intracerebral hemorrhage senile patient were selected and randomly divided into groups: the combined group (50 people and the control group (50 people. The senile patients in the control group were treated with conventional therapy and the senile patients in the combined group were treated with edaravone combined with torasemide and conventional therapy. Inflammatory, coagulation function and hemorheology were compared before and after seven days therapy. Results: Before treatment, inflammatory, coagulation function and hemorheology of two groups showed no statistically significant difference. Inflammatory (IL-6, IL-8, CRP, and TNF-α and hemorheology (WLV, WMV, WHV, PV, and PCV of two groups decreased significantly than before treatment (P<0.05, coagulation function (PT, APPT of two groups increased significantly than before treatment (P<0.05; Coagulation function (PT, APPT and hemorheology (WLV, WMV, WHV, PV, and PCV of the combined groups after treatment increased significantly than control group after treatment (P<0.05, inflammatory (IL-6, IL-8, CRP, and TNF-α and FIB of the combined groups after treatment decreased significantly than control group after treatment (P<0.05. Conclusions: Edaravone combined with torasemide can perfect effectively inflammatory, coagulation function and hemorheology on senile patient acute intracerebral hemorrhage, it has important clinical significance for senile patient acute intracerebral hemorrhage treatment.

FcγRIIIa expression on monocytes in rheumatoid arthritis: role in immune-complex stimulated TNF production and non-response to methotrexate therapy.

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Dawn L Cooper

Full Text Available OBJECTIVE: The expression of FcγRIIIa/CD16 may render monocytes targets for activation by IgG-containing immune complexes (IC. We investigated whether FcγRIIIa/CD16 was upregulated in rheumatoid arthritis (RA, associated with TNF production in response to IC-stimulation, and if this predicted response to methotrexate therapy. METHODS: FcγRIIIa/CD16 expression on CD14(low and CD14++ monocytes was measured by flow cytometry in healthy controls and RA patients (early and long-standing disease. Intracellular TNF-staining was carried out after in vitro LPS or heat-aggregated immunoglobulin (HAG activation. FcγRIIIa/CD16 expression pre- and post-steroid/methotrexate treatment was examined. RESULTS: Increased FcγRIIIa/CD16 expression on CD14++ monocytes in long-standing RA patients compared to controls was demonstrated (p = 0.002 with intermediate levels in early-RA patients. HAG-induced TNF-production in RA patients was correlated with the percentage of CD14++ monocytes expressing FcγRIIIa/CD16 (p<0.001. The percentage of CD14++ monocytes expressing FcγRIIIa/CD16 at baseline in early DMARD-naïve RA patients was negatively correlated with DAS28-ESR improvement 14-weeks post-methotrexate therapy (p = 0.003 and was significantly increased in EULAR non-responders compared to moderate (p = 0.01 or good responders (p = 0.003. FcγRIIIa/CD16 expression was not correlated with age, presence of systemic inflammation or autoantibody titers. CONCLUSION: Increased FcγRIIIa/CD16 expression on CD14++ monocytes in RA may result in a cell that has increased responsiveness to IC-stimulation. This monocyte subset may contribute to non-response to methotrexate therapy.

FcγRIIIa Expression on Monocytes in Rheumatoid Arthritis: Role in Immune-Complex Stimulated TNF Production and Non-Response to Methotrexate Therapy

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Cooper, Dawn L.; Martin, Stephen G.; Robinson, James I.; Mackie, Sarah L.; Charles, Christopher J.; Nam, Jackie; Consortium, YEAR; Isaacs, John D.; Emery, Paul; Morgan, Ann W.

2012-01-01

Objective The expression of FcγRIIIa/CD16 may render monocytes targets for activation by IgG-containing immune complexes (IC). We investigated whether FcγRIIIa/CD16 was upregulated in rheumatoid arthritis (RA), associated with TNF production in response to IC-stimulation, and if this predicted response to methotrexate therapy. Methods FcγRIIIa/CD16 expression on CD14low and CD14++ monocytes was measured by flow cytometry in healthy controls and RA patients (early and long-standing disease). Intracellular TNF-staining was carried out after in vitro LPS or heat-aggregated immunoglobulin (HAG) activation. FcγRIIIa/CD16 expression pre- and post-steroid/methotrexate treatment was examined. Results Increased FcγRIIIa/CD16 expression on CD14++ monocytes in long-standing RA patients compared to controls was demonstrated (p = 0.002) with intermediate levels in early-RA patients. HAG-induced TNF-production in RA patients was correlated with the percentage of CD14++ monocytes expressing FcγRIIIa/CD16 (p<0.001). The percentage of CD14++ monocytes expressing FcγRIIIa/CD16 at baseline in early DMARD-naïve RA patients was negatively correlated with DAS28-ESR improvement 14-weeks post-methotrexate therapy (p = 0.003) and was significantly increased in EULAR non-responders compared to moderate (p = 0.01) or good responders (p = 0.003). FcγRIIIa/CD16 expression was not correlated with age, presence of systemic inflammation or autoantibody titers. Conclusion Increased FcγRIIIa/CD16 expression on CD14++ monocytes in RA may result in a cell that has increased responsiveness to IC-stimulation. This monocyte subset may contribute to non-response to methotrexate therapy. PMID:22235253

Basics of acute stroke treatment

International Nuclear Information System (INIS)

Haass, A.

2005-01-01

Acute stroke presents an emergency that requires immediate referral to a specialized hospital, preferably with a stroke unit. Disability and mortality are reduced by 30% in patients treated in stroke units compared to those treated on regular wards, even if a specialized team is present on the ward. Systolic blood pressure may remain high at 200-220 mmHg in the acute phase and should not be lowered too quickly. Further guidelines for basic care include: optimal O 2 delivery, blood sugar levels below 100-150 mg%, and lowering body temperature below 37.5 C using physical means or drugs. Increased intracranial pressure should be treated by raising the upper body of the patient, administration of glycerol, mannitol, and/or sorbitol, artificial respiration, and special monitoring of Tris buffer. Decompressive craniectomy may be considered in cases of ''malignant'' media stroke and expansive cerebellar infarction. Fibrinolysis is the most effective stroke treatment and is twice as effective in the treatment of stroke than myocardial infarction. Fibrinolysis may be initiated within 3 h of a stroke in the anterior circulation. If a penumbra is detectable by ''PWI-DWI mismatch MRI,'' specialized hospitals may perform fibrinolysis up to 6 h after symptom onset. In cases of stroke in the basilar artery, fibrinolysis may be performed even later after symptom onset. Intra-arterial fibrinolysis is performed in these cases using rt-PA or urokinase. Follow-up treatment of stroke patients should not only address post-stroke depression and neuropsychological deficits, but also include patient education about risk factors such as high blood pressure, diabetes mellitus, and cardiac arrhythmias. (orig.) [de

DNA-thioguanine nucleotide concentration and relapse-free survival during maintenance therapy of childhood acute lymphoblastic leukaemia (NOPHO ALL2008): a prospective substudy of a phase 3 trial.

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Nielsen, Stine Nygaard; Grell, Kathrine; Nersting, Jacob; Abrahamsson, Jonas; Lund, Bendik; Kanerva, Jukka; Jónsson, Ólafur Gísli; Vaitkeviciene, Goda; Pruunsild, Kaie; Hjalgrim, Lisa Lyngsie; Schmiegelow, Kjeld

2017-04-01

Adjustment of mercaptopurine and methotrexate maintenance therapy of acute lymphoblastic leukaemia by leucocyte count is confounded by natural variations. Cytotoxicity is primarily mediated by DNA-incorporated thioguanine nucleotides (DNA-TGN). The aim of this study was to establish whether DNA-TGN concentrations in blood leucocytes during maintenance therapy are associated with relapse-free survival. In this substudy of the NOPHO ALL2008 phase 3 trial done in 23 hospitals in seven European countries (Denmark, Estonia, Finland, Iceland, Lithuania, Norway, and Sweden), we analysed data from centralised and blinded analyses of 6-mercaptopurine and methotrexate metabolites in blood samples from patients with non-high-risk childhood acute lymphoblastic leukaemia. Eligible patients were aged 1·0-17·9 years; had been diagnosed with non-high-risk precursor B-cell or T-cell leukaemia; had been treated according to the Nordic Society of Pediatric Hematology and Oncology ALL2008 protocol; and had reached maintenance therapy in first remission. Maintenance therapy was (mercaptopurine 75 mg/m 2 once per day and methotrexate 20 mg/m 2 once per week, targeted to a leucocyte count of 1·5-3·0 × 10 9 cells per L). We measured DNA-TGN and erythrocyte concentrations of TGN nucleotides, methylated mercaptopurine metabolites, and methotrexate polyglutamates. The primary objective was the association of DNA-TGN concentrations and 6-mercaptopurine and methotrexate metabolites with relapse-free survival. The secondary endpoint was the assessment of DNA-TGN concentration and 6-mercaptopurine and methotrexate metabolites during maintenance therapy phase 2. Between Nov 26, 2008 and June 14, 2016, 1509 patients from the NOPHO ALL2008 study were assessed for eligibility in the DNA-TGN substudy, of which 918 (89%) of 1026 eligible patients had at least one DNA-TGN measurement and were included in the analyses. Median follow-up was 4·6 years (IQR 3·1-6·1). Relapse-free survival was

Modifications in Lipid Levels Are Independent of Serum TNF-α in Rheumatoid Arthritis: Results of an Observational 24-Week Cohort Study Comparing Patients Receiving Etanercept Plus Methotrexate or Methotrexate as Monotherapy

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Norma Alejandra Rodriguez-Jimenez

2014-01-01

Full Text Available Objective. To compare the modifications in lipids between patients with rheumatoid arthritis (RA receiving etanercept plus methotrexate (ETA + MTX versus methotrexate (MTX and their relationship with serum levels of tumor necrosis factor-alpha (TNF-α. Methods. In an observational cohort study, we compared changes in lipid levels in patients receiving ETA + MTX versus MTX in RA. These groups were assessed at baseline and at 4 and 24 weeks, measuring clinical outcomes, total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C, low-density lipoprotein cholesterol, and TNF-α. Results. Baseline values for lipid levels were similar in both groups. HDL-C levels increased significantly only in the ETA + MTX group (from 45.5 to 50.0 mg/dL at 4 weeks, a 10.2% increase, P<0.001, and to 56.0 mg/dL at 24 weeks, a 25.1% increase, P<0.001, while other lipids underwent no significant changes. ETA + MTX also exhibited a significant increase in TNF-α (44.8 pg/mL at baseline versus 281.4 pg/mL at 24 weeks, P<0.001. The MTX group had no significant changes in lipids or TNF-α. Significant differences in HDL-C between groups were observed at 24 weeks (P=0.04 and also in TNF-α  (P=0.01. Conclusion. HDL-C levels increased significantly following treatment with ETA + MTX, without a relationship with decrease of TNF-α.

Sphenopalatine Ganglion Block for the Treatment of Acute Migraine Headache

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Mohamed Binfalah

2018-01-01

Full Text Available Transnasal sphenopalatine ganglion block is emerging as is an attractive and effective treatment modality for acute migraine headaches, cluster headache, trigeminal neuralgia, and several other conditions. We assessed the efficacy and safety of this treatment using the Sphenocath® device. 55 patients with acute migraine headaches underwent this procedure, receiving 2 ml of 2% lidocaine in each nostril. Pain numeric rating scale (baseline, 15 minutes, 2 hours, and 24 hours and patient global impression of change (2 hours and 24 hours after treatment were recorded. The majority of patients became headache-free at 15 minutes, 2 hours, and 24 hours after procedure (70.9%, 78.2%, and 70.4%, resp.. The rate of headache relief (50% or more reduction in headache intensity was 27.3% at 15 minutes, 20% at 2 hours, and 22.2% at 24 hours. The mean pain numeric rating scale decreased significantly at 15 minutes, 2 hours, and 24 hours, respectively. Most patients rated the results as very good or good. The procedure was well-tolerated with few adverse events. This treatment is emerging as an effective and safe option for management of acute migraine attacks.

Adult Acute Myeloid Leukemia Treatment (PDQ®)—Health Professional Version

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Acute myeloid (myelogenous) leukemia (AML) treatment options include chemotherapy, radiation therapy, stem cell transplant, and other medications. Cytogenetic analysis helps predict treatment outcomes. Get detailed information about AML in this summary for clinicians.

Risk of Adverse Pregnancy Outcome After Paternal Exposure to Methotrexate Within 90 Days Before Pregnancy

DEFF Research Database (Denmark)

Eck, Lasse Karlsen; Jensen, Thomas Bo; Mastrogiannis, Dimitrios

2017-01-01

OBJECTIVE: To study the association between paternal exposure to methotrexate within the 90-day period before pregnancy and congenital malformations and stillbirth in the offspring. METHODS: We conducted a nationwide register study. Our cohort consisted of all live births in Denmark between 1997...... group and no increased risk of preterm birth (adjusted OR 1.31, 95% CI 0.66-2.59) among the children from exposed fathers. CONCLUSION: We found no association between paternal exposure to methotrexate within 90 days before pregnancy and congenital malformations, stillbirths, or preterm birth. Available...

Acute intermittent porphyria: Diagnostic dilemma and treatment options

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Mohan Deep Kaur

2015-01-01

Full Text Available Acute intermittent porphyria (AIP presents with diverse group of symptoms making its early diagnosis difficult. Delaying diagnosis and treatment of AIP can be fatal or can cause long term or permanent neurological damage. We present here a case report of AIP where the diagnosis was missed. The diversity of symptoms and details concerning the treatment options for AIP are discussed.

Acute intermittent porphyria: Diagnostic dilemma and treatment options

Science.gov (United States)

Kaur, Mohan Deep; Hazarika, Nita; Saraswat, Namita; Sood, Rajesh

2015-01-01

Acute intermittent porphyria (AIP) presents with diverse group of symptoms making its early diagnosis difficult. Delaying diagnosis and treatment of AIP can be fatal or can cause long term or permanent neurological damage. We present here a case report of AIP where the diagnosis was missed. The diversity of symptoms and details concerning the treatment options for AIP are discussed. PMID:26330726

Neoadjuvant chemotherapy with cisplatin and methotrexate in patients with muscle-invasive bladder tumours

DEFF Research Database (Denmark)

Sengeløv, Lisa; von der Maase, Hans; Lundbeck, Finn

2002-01-01

This prospective, randomized study based on two associated trials was designed to evaluate the effect of neoadjuvant chemotherapy with cisplatin and methotrexate with folinic acid rescue or no chemotherapy prior to local treatment in patients with T2-T4b, NX-3, MO transitional cell carcinoma...... was 12.9 months. Median time to progression was 14.2 months with chemotherapy and 11.4 months without chemotherapy. The actuarial 5-year overall survival rate for all 153 patients was 29%, and 29% for both treatment groups. Multivariate analyses showed that T-stage, tumour size and serum creatinine were...... independent prognostic factors for survival. The cystectomy trial included 33 patients. Median survival was 78.9 months, 82.5 months with chemotherapy and 45.8 months without chemotherapy (p = 0.76). The radiotherapy trial included 120 patients. The median survival was 17.6 months. Median survival was 19...

Microbiology and Treatment of Acute Apical Abscesses

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Rôças, Isabela N.

2013-01-01

SUMMARY Acute apical abscess is the most common form of dental abscess and is caused by infection of the root canal of the tooth. It is usually localized intraorally, but in some cases the apical abscess may spread and result in severe complications or even mortality. The reasons why dental root canal infections can become symptomatic and evolve to severe spreading and sometimes life-threatening abscesses remain elusive. Studies using culture and advanced molecular microbiology methods for microbial identification in apical abscesses have demonstrated a multispecies community conspicuously dominated by anaerobic bacteria. Species/phylotypes commonly found in these infections belong to the genera Fusobacterium, Parvimonas, Prevotella, Porphyromonas, Dialister, Streptococcus, and Treponema. Advances in DNA sequencing technologies and computational biology have substantially enhanced the knowledge of the microbiota associated with acute apical abscesses and shed some light on the etiopathogeny of this disease. Species richness and abundance and the resulting network of interactions among community members may affect the collective pathogenicity and contribute to the development of acute infections. Disease modifiers, including transient or permanent host-related factors, may also influence the development and severity of acute abscesses. This review focuses on the current evidence about the etiology and treatment of acute apical abscesses and how the process is influenced by host-related factors and proposes future directions in research, diagnosis, and therapeutic approaches to deal with this disease. PMID:23554416

Rapid, radiochemical-ligand binding assay for methotrexate

International Nuclear Information System (INIS)

Caston, J.D.

1976-01-01

A radiochemical ligand binding assay for methotrexate is provided. A binder factor comprising a partially purified dihydrofolic acid reductase preparation is employed. The binder factor is conveniently prepared by homogenizing a factor containing animal organ such as liver, and extracting with isotonic saline and ammonium sulfate. A binder cofactor, NADPH 2 , is also employed in the binding reaction. The procedure contemplates both direct and sequential assay techniques, and it is not interfered with by vast excesses of many natural folate derivatives. 12 claims, 6 drawing figures

Teaching methotrexate self-injection with a web-based video maintains patient care while reducing healthcare resources: a pilot study.

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Katz, Steven J; Leung, Sylvia

2015-01-01

The aim of the study was to compare standard nurse-led methotrexate self-injection patient education to a web-based methotrexate self-injection education video in conjunction with standard teaching on patient self-confidence for self-injection, as well as patient satisfaction, patient knowledge and teaching time. Consecutive rheumatology patients seen for methotrexate self-injection education were enrolled. Prior to education, patient self-confidence for self-injection, age, gender and education were recorded. Patients were randomized 1:1 to standard teaching or the intervention: a 12-min methotrexate self-injection education video followed by further in-person nurse education. Patients recorded their post-education confidence for self-injection, satisfaction with the teaching process and answered four specific questions testing knowledge on methotrexate self-injection. The time spent providing direct education to the patient was recorded. Twenty-nine patients participated in this study: 15 had standard (C) teaching and 14 were in the intervention group (I). Average age, gender and education level were similar in both groups. Both groups were satisfied with the quality of teaching. There was no difference in pre-confidence (C = 5.5/10 vs. I = 4.7/10, p = 0.44) or post-confidence (C = 8.8, I = 8.8, p = 0.93) between the groups. There was a trend toward improved patient knowledge in the video group versus the standard group (C = 4.7/6, I = 5.5/6, p = 0.15). Nurse teaching time was less in the video group (C = 60 min, I = 44 min, p = 0.012), with men requiring longer education time than women across all groups. An education video may be a good supplement to standard in-person nurse teaching for methotrexate self-injection. It equals the standard teaching practise with regard to patient satisfaction, confidence and knowledge while decreasing teaching time by 25 %.

Duration of adrenal insufficiency during treatment for childhood acute lymphoblastic leukemia

DEFF Research Database (Denmark)

Vestergaard, Therese Risom; Juul, Anders; Lausten-Thomsen, Ulrik

2011-01-01

Children with acute lymphoblastic leukemia (ALL) recive high doses of glucocorticosteroid as part of their treatment. This may lead to suppression of the hypothalamic-pituitary-adrenal axis, acute adrenal insufficiency, and ultimately to life-threatening conditions. This study explores the adrena...

[Usefulness of fenspiride in the treatment of acute otitis media in children].

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Zielnik-Jurkiewicz, Beata; Jurkiewicz, Dariusz

2005-06-01

Acute otitis media is very general disease and concerns every child practically. The shortening the time of treatment as well as quick decrease of symptoms, and mainly the pain have large meaning in treatment of this disease. Combined treatment of fenspiride and typical treatment of otitis media permits as our investigations show on quicker and observed at children's larger number decrease of symptoms in children with acute otitis media. The aim of the study was to observe effectiveness of combined treatment with antibiotic and fenspiride in children with acute otitis media. The study comprised 40 children (mean age 8.2 years). The diagnosis of acute otitis media based on medical history data, otolaryngological examination and audiometry (tone and impedance). Children with GERD, hypersensitivity to amoxicillin and fenspiride as well as hypertrophy of adenoid were excluded from the study. Children were divided in two equal groups randomly. All children received amoxicillin in dose 80 mg/kg/day in three partite doses (Amotaks, Polfa Tarchomin Poland) as well as oxymethazolin 0.05% nasal drops 3 x day 1-2 drops (0.05% Nasivin, Merck Germany). In children from second group fenspiride was applied in dose 2 ml/kg/day in three divided doses (Eurespal, Servier Francja) additionally. Treatment was provided by 10 days. During the treatment parents made record of recession in 10 point scale, estimating following parameters: the pain of ear, bother, raised the temperature of body, loss of appetite, vomiting, diarrhea, otorrhea and crying. After end of treatment control otolaryngological and audiological examinations were performed. In studied children symptoms were similar, and the pain of ear was in both groups main suffering. Vomiting and diarrhea the most seldom were observed. In children with acute otitis media treated additionally with fenspiride statistically significant (pfenspiride in comparison to children treated only with antibiotic. Earlier return of hearing and

Success and spontaneous pregnancy rates following systemic methotrexate versus laparoscopic surgery for tubal pregnancies: A randomized trial

DEFF Research Database (Denmark)

Krag Moeller, Lars Bo; Moeller, Charlotte; Thomsen, Sten Grove

2009-01-01

. A total of 106 women diagnosed with ectopic pregnancy (EP). Methods. Between March 1997 and September 2000, 1,265 women were diagnosed with EP, 395 (31%) were eligible, 109 (9%) were randomized of whom 106 had an EP. The study was originally powered to a sample size of 422 patients. The women were......Objective. To determine which treatment should be offered to women with a non-ruptured tubal pregnancy: a single dose of methotrexate (MTX) or laparoscopic surgery. Design. Prospective, randomized, open multicenter study. Setting. Seven Danish departments of obstetrics and gynecology. Sample...... (n.s.). Conclusions. In women with an EP, who are hemodynamically stable and wishing to preserve their fertility, medical treatment with single dose MTX tends to be equal to treatment with laparoscopic surgery regarding success rate, complications, and subsequent fertility. Although the two treatment...

Topical methotrexate pretreatment enhances the therapeutic effect of topical 5-aminolevulinic acid-mediated photodynamic therapy on hamster buccal pouch precancers

OpenAIRE

Deng-Fu Yang; Jeng-Woei Lee; Hsin-Ming Chen; Yih-Chih Hsu

2014-01-01

Topical 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) is effective for treatment of human oral precancerous lesions. This animal study aimed to assess whether topical methotrexate (MTX) pretreatment could enhance the therapeutic effect of topical ALA-PDT on hamster buccal pouch precancerous lesions. Methods: Twenty hamster buccal pouch precancerous lesions were treated with either topical ALA-PDT with topical MTX pretreatment (topical MTX-ALA-PDT group, n = 10) or topical A...

Vinorelbine Potently Induces Placental Cell Death, Does Not Harm Fertility and is a Potential Treatment for Ectopic Pregnancy

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Roxanne Hastie

2018-03-01

Full Text Available Ectopic pregnancies complicate 1–2 pregnancies and are a leading cause of maternal death. An effective oral drug therapy that replaces surgery might make its treatment safer, cheaper, simpler and therefore more widely accessible. The only current medical treatment offered to women is intramuscular methotrexate, but this only reliably resolves smaller ectopic pregnancies. As such, many ectopic pregnancies require surgical excision. We show that vinorelbine, an orally available chemotherapeutic agent, potently induced placental cell death but did not harm fertility in mice. Vinorelbine was 100–1000 times more potent than methotrexate in inducing placental cell death in vitro, and more potent than combination methotrexate and gefitinib (another proposed treatment for ectopic pregnancy being evaluated in phase III trials. Mechanistically, it caused microtubule condensation, blocked mitosis and activated the apoptosis cascade in placental cells. Vinorelbine was more efficacious than methotrexate ± gefitinib in reducing the volume of placental cell tumors xenografted subcutaneously in SCID mice. Mice exposed to vinorelbine and allowed to breed, following a four week washout period, displayed normal fertility, however long-term fertility was not assessed. Human Fallopian tubes treated with vinorelbine did not exhibit up-regulation of apoptosis molecules. Our findings show that placental cells appear sensitive to vinorelbine and it has potential as a tablet-only approach to treat ectopic pregnancy. Keywords: Ectopic pregnancy, Vinorelbine, Methotrexate, Placenta, Treatment

Long-term tolerability of telcagepant for acute treatment of migraine in a randomized trial

DEFF Research Database (Denmark)

Connor, Kathryn M; Aurora, Sheena K; Loeys, Tom

2011-01-01

To evaluate the long-term tolerability of telcagepant for acute treatment of intermittent migraine attacks. Background.- Telcagepant is a calcitonin gene-related peptide (CGRP) receptor antagonist being investigated for the acute treatment of migraine....

Collateral methotrexate resistance in cisplatin-selected murine leukemia cells

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Bhushan A.

1999-01-01

Full Text Available Resistance to anticancer drugs is a major cause of failure of many therapeutic protocols. A variety of mechanisms have been proposed to explain this phenomenon. The exact mechanism depends upon the drug of interest as well as the tumor type treated. While studying a cell line selected for its resistance to cisplatin we noted that the cells expressed a >25,000-fold collateral resistance to methotrexate. Given the magnitude of this resistance we elected to investigate this intriguing collateral resistance. From a series of investigations we have identified an alteration in a membrane protein of the resistant cell as compared to the sensitive cells that could be the primary mechanism of resistance. Our studies reviewed here indicate decreased tyrosine phosphorylation of a protein (molecular mass = 66 in the resistant cells, which results in little or no transfer of methotrexate from the medium into the cell. Since this is a relatively novel function for tyrosine phosphorylation, this information may provide insight into possible pharmacological approaches to modify therapeutic regimens by analyzing the status of this protein in tumor samples for a better survival of the cancer patients.

Maternal depressive symptoms in pediatric major depressive disorder: relationship to acute treatment outcome.

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Kennard, Betsy D; Hughes, Jennifer L; Stewart, Sunita M; Mayes, Taryn; Nightingale-Teresi, Jeanne; Tao, Rongrong; Carmody, Thomas; Emslie, Graham J

2008-06-01

In the present study, we assess maternal depressive symptoms at the beginning and end of treatment to investigate the possible reciprocal relationship of maternal illness with the child's depressive illness and treatment. We present data on 146 children and their mothers who were participating in a pediatric acute treatment study of fluoxetine. Patients were assessed with the Children's Depression Rating Scale-Revised at baseline and at each treatment visit. Mothers completed the Quick Inventory of Depressive Symptomatology-Self Report at baseline and end of acute treatment. Thirty percent of mothers had moderate to severe levels of depressive symptoms at the child's baseline assessment. Overall, mothers reported improvement in maternal depressive symptoms at the end of their child's acute treatment, although maternal depression was not specifically targeted for intervention. Furthermore, mother's depressive symptoms appear to be associated with the child's depression severity both at the beginning and end of treatment. Mothers with higher levels of depressive symptoms had children with higher levels of depression severity at baseline and over the course of treatment. However, maternal depressive symptoms at baseline had no association with the rate of improvement of child depression severity. This study indicates a positive relationship between the depression severity of mothers and their children. These findings highlight potential areas of intervention in the acute treatment of childhood depression.

Chronic plaque psoriasis: streptococcus pyogenes throat carriage rate and therapeutic response to oral antibiotics in comparison with oral methotrexate

International Nuclear Information System (INIS)

Raza, N.; Usman, M.; Hameed, A.

2007-01-01

To determine the throat carriage rate of Streptococcus pyogenes in patients having chronic plaque psoriasis and the effect of antibiotics as compared with that of oral methotrexate. Forty patients and 40 age and gender-matched controls were selected. Throat swab for culture of Streptococcus pyogenes was taken from each patient and control. All patients were treated with oral Penicillin V 250 mg, 6 hourly, and oral Rifampicin, 600 mg daily, for 10 days. Pre- and post therapy 'Psoriasis Area and Severity Index' (PASI) were compared. Thirty of these 40 patients were later given oral methotrexate, 5-10 mg weekly, for 04 weeks and pre- and post-therapy PASI were compared. Chi-square and paired-samples t-test were used for data analysis. Throat swab cultures were positive for Streptococcus pyogenes in 05 (12.5%) patients and none (0%) of the controls (p=0.02). Mean pre- and postantibiotic therapy PASI were 15.92 + 05.94 and 15.19 + 06.17 respectively (p=0.078). Mean pre- and postmethotrexate PASI were 15.81+ 5.55 and 8.79 + 4.19 respectively (p <0.01). Throat carriage of Streptococcus pyogenes is common in patients with chronic plaque psoriasis. Short-term antibiotic treatment has no role in routine treatment of chronic plaque psoriasis. However, it would be worthwhile to consider the effects of long term antibiotics on chronic plaque psoriasis. (author)

[Cost effectiveness in treatment of acute myeloid leukemia].

Science.gov (United States)

Nordmann, P; Schaffner, A; Dazzi, H

2000-12-23

Although the rise in health costs is a widely debated issue, in Switzerland it was until recently taken for granted that patients are given the best available treatment regardless of cost. An example of a disease requiring costly treatment is acute myelogenous leukaemia (AML). To relate cost to benefit we calculated expenditure per life years gained. To assess costs we determined the real cost of treatment up to total remission, followed by consolidation or withdrawal of treatment or death. For survival time exceeding the 2-year observation period we used data from recent literature. The average cost of treatment ranges up to 107,592 Swiss francs (CHF). In 1997 we treated 23 leukaemia patients at Zurich University Hospital and gained a total of 210 life years. This represents an average cost of CHF 11,741 per life year gained. Chief cost items were therapy and personnel costs for nursing staff, followed by hotel business and personnel costs for doctors and diagnosis. Our results for AML treatment are far removed from the $61,500 ranging up to $166,000 discussed in the literature as the "critical" QALY (quality adjusted life years) value. This is the first time the actual costs of AML therapy have been shown for a Swiss cohort. Despite high initial treatment costs and success only in a limited number of patients, the expenditure per QALY is surprisingly low and shows clearly the effectiveness of apparently costly acute medicine.

Long-term cerebral metabolite changes on proton magnetic resonance spectroscopy in patients cured of acute lymphoblastic leukemia with previous intrathecal methotrexate and cranial irradiation prophylaxis

International Nuclear Information System (INIS)

Chan Yuleung; Roebuck, Derek J.; Yuen Manpan; Yeung Kawai; Lau Kamying; Li Chikong; Chik Kiwai

2001-01-01

Purpose: To evaluate the long-term brain metabolite changes on 1 H-MRS in acute lymphoblastic leukemia (ALL) patients who had intrathecal methotrexate (ITMTX) and cranial irradiation (CRT) for central nervous system (CNS) prophylaxis against CNS relapse. Methods and Materials: Thirty-seven ALL patients (12 females, 25 males) with history of ITMTX and CRT for CNS prophylaxis were studied. Age ranges at the time of diagnosis and at magnetic resonance examination were 0.8-13 years and 12-27 years, respectively. The interval since diagnosis was 5.6-19 years. T2-weighted and gradient-recalled echo (GRE) magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy ( 1 H-MRS) were performed to assess brain injury. Results: On MRI, 3 leukoencephalopathy (LEP) and 1 infarct were detected. Twenty-two patients had evidence of hemosiderin. On 1 H-MRS no statistically significant difference in choline (Cho)/creatine (Cr) and N-acetylaspartate (NAA)/Cr was associated with LEP. A lower Cho/Cr (p=0.006) and NAA/Cr (p=0.078) was observed in brains with hemosiderin. Linear-regression analysis showed no statistically significant relationship between NAA/Cr or Cho/Cr with age at diagnosis, but there was a statistically significant decreasing trend of NAA/Cr and Cho/Cr with the interval since diagnosis. Conclusion: Long-term brain injury in ALL survivors after CNS prophylaxis with ITMTX and CRT was reflected by decreasing NAA/Cr and Cho/Cr with the interval since diagnosis. The lower Cho/Cr associated with hemosiderin but not LEP suggested a different pathophysiology for these brain lesions

Minimally Invasive Surgical Treatment of Acute Epidural Hematoma: Case Series

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Weijun Wang

2016-01-01

Full Text Available Background and Objective. Although minimally invasive surgical treatment of acute epidural hematoma attracts increasing attention, no generalized indications for the surgery have been adopted. This study aimed to evaluate the effects of minimally invasive surgery in acute epidural hematoma with various hematoma volumes. Methods. Minimally invasive puncture and aspiration surgery were performed in 59 cases of acute epidural hematoma with various hematoma volumes (13–145 mL; postoperative follow-up was 3 months. Clinical data, including surgical trauma, surgery time, complications, and outcome of hematoma drainage, recovery, and Barthel index scores, were assessed, as well as treatment outcome. Results. Surgical trauma was minimal and surgery time was short (10–20 minutes; no anesthesia accidents or surgical complications occurred. Two patients died. Drainage was completed within 7 days in the remaining 57 cases. Barthel index scores of ADL were ≤40 (n=1, 41–60 (n=1, and >60 (n=55; scores of 100 were obtained in 48 cases, with no dysfunctions. Conclusion. Satisfactory results can be achieved with minimally invasive surgery in treating acute epidural hematoma with hematoma volumes ranging from 13 to 145 mL. For patients with hematoma volume >50 mL and even cerebral herniation, flexible application of minimally invasive surgery would help improve treatment efficacy.

Mixed-phenotype acute leukemia: state-of-the-art of the diagnosis, classification and treatment.

Science.gov (United States)

Cernan, Martin; Szotkowski, Tomas; Pikalova, Zuzana

2017-09-01

Mixed-phenotype acute leukemia (MPAL) is a heterogeneous group of hematopoietic malignancies in which blasts show markers of multiple developmental lineages and cannot be clearly classified as acute myeloid or lymphoblastic leukemias. Historically, various names and classifications were used for this rare entity accounting for 2-5% of all acute leukemias depending on the diagnostic criterias used. The currently valid classification of myeloid neoplasms and acute leukemia published by the World Health Organization (WHO) in 2016 refers to this group of diseases as MPAL. Because adverse cytogenetic abnormalities are frequently present, MPAL is generally considered a disease with a poor prognosis. Knowledge of its treatment is limited to retrospective analyses of small patient cohorts. So far, no treatment recommendations verified by prospective studies have been published. The reported data suggest that induction therapy for acute lymphoblastic leukemia followed by allogeneic hematopoietic cell transplantation is more effective than induction therapy for acute myeloid leukemia or consolidation chemotherapy. The establishment of cooperative groups and international registries based on the recent WHO criterias are required to ensure further progress in understanding and treatment of MPAL. This review summarizes current knowledge on the diagnosis, classification, prognosis and treatment of MPAL patients.

Monitoring and treatment of acute gastrointestinal bleeding.

Science.gov (United States)

Lenjani, Basri; Zeka, Sadik; Krasniqi, Salih; Bunjaku, Ilaz; Jakupi, Arianit; Elshani, Besni; Xhafa, Agim

2012-01-01

Acute gastrointestinal bleeding-massive acute bleeding from gastrointestinal section is one of the most frequent forms of acute abdomen. The mortality degree in emergency surgery is about 10%. It's very difficult to identify the place of bleeding and etiology. The important purpose of this research is to present the cases of acute gastrointestinal bleeding from the patients which were monitored and treated at The University Clinical Center of Kosova-Emergency Center in Pristina. These inquests included 137 patients with acute gastrointestinal bleeding who were treated in emergency center of The University Clinical Center in Pristina for the period from January 2005 until December 2006. From 137 patients with acute gastrointestinal bleeding 41% or 29% was female and 96% or 70.1% male. Following the sex we gained a high significant difference of statistics (p < 0.01). The gastrointestinal bleeding was two times more frequent in male than in female. Also in the age-group we had a high significant difference of statistics (p < 0.01) 63.5% of patients were over 55 years old. The mean age of patients with an acute gastrointestinal bleeding was 58.4 years SD 15.8 age. The mean age for female patients was 56.4 age SD 18.5 age. The patients with arterial systolic pressure under 100 mmHg have been classified as patients with hypovolemic shock. They participate with 17.5% in all prevalence of acute gastrointestinal bleeding. From the number of prevalence 2 {1.5%} patients have been diagnosed with peptic ulcer, 1 {0.7%} as gastric perforation and 1 {0.7%} with intestine ischemia. Abdominal Surgery and Intensive Care 2 or 1.5% died, 1 at intensive care unit and 1 at nephrology. As we know the severe condition of the patients with gastrointestinal bleeding and etiology it is very difficult to establish, we need to improve for the better conditions in our emergency center for treatment and initiation base of clinic criteria.

High-dose methotrexate following intravitreal methotrexate administration in preventing central nervous system involvement of primary intraocular lymphoma.

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Akiyama, Hiroki; Takase, Hiroshi; Kubo, Fumito; Miki, Tohru; Yamamoto, Masahide; Tomita, Makoto; Mochizuki, Manabu; Miura, Osamu; Arai, Ayako

2016-10-01

In order to prevent central nervous system (CNS) involvement and improve the prognosis of primary intraocular lymphoma (PIOL), we prospectively evaluated the efficacy of combined therapy using intravitreal methotrexate (MTX) and systemic high-dose MTX on treatment-naïve PIOL. Patients with newly diagnosed PIOL whose lymphoma was limited to the eyes were enrolled. The patients were treated with weekly intravitreal MTX until the ocular lesions were resolved, followed by five cycles of systemic high-dose MTX (3.5 g/m 2 ) every other week. Ten patients were enrolled in this study and completed the treatment. All patients achieved complete response for their ocular lesions with rapid decrease of intravitreal interleukin-10 concentration. Adverse events of intravitreal and systemic high-dose MTX were mild and tolerable. With a median follow-up of 29.5 months, four patients (40%) experienced the CNS disease development and the mean CNS lymphoma-free survival (CLFS) time was 51.1 months. Two-year CLFS, which was the primary end-point of the study, was 58.3% (95% confidence interval, 23.0-82.1%). In contrast, eight patients were treated with intravitreal MTX alone in our institute, and their 2-year CLFS was 37.5% (95% confidence interval, 8.7-67.4%). In conclusion, systemic high-dose MTX following intravitreal MTX is feasible and might be effective in preventing CNS involvement of PIOL. Further arrangements are worth considering in order to improve the effects. This study was registered with UMIN Clinical Trials Registry (UMIN000003921). © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

St. John's wort significantly increased the systemic exposure and toxicity of methotrexate in rats

Energy Technology Data Exchange (ETDEWEB)

Yang, Shih-Ying [Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung, Taiwan (China); Juang, Shin-Hun [Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung, Taiwan (China); Department of Medical Research, China Medical University Hospital, Taichung, Taiwan (China); Tsai, Shang-Yuan; Chao, Pei-Dawn Lee [School of Pharmacy, China Medical University, Taichung, Taiwan (China); Hou, Yu-Chi, E-mail: hou5133@gmail.com [School of Pharmacy, China Medical University, Taichung, Taiwan (China); Department of Medical Research, China Medical University Hospital, Taichung, Taiwan (China)

2012-08-15

St. John's wort (SJW, Hypericum perforatum) is one of the popular nutraceuticals for treating depression. Methotrexate (MTX) is an immunosuppressant with narrow therapeutic window. This study investigated the effect of SJW on MTX pharmacokinetics in rats. Rats were orally given MTX alone and coadministered with 300 and 150 mg/kg of SJW, and 25 mg/kg of diclofenac, respectively. Blood was withdrawn at specific time points and serum MTX concentrations were assayed by a specific monoclonal fluorescence polarization immunoassay method. The results showed that 300 mg/kg of SJW significantly increased the AUC{sub 0−t} and C{sub max} of MTX by 163% and 60%, respectively, and 150 mg/kg of SJW significantly increased the AUC{sub 0−t} of MTX by 55%. In addition, diclofenac enhanced the C{sub max} of MTX by 110%. The mortality of rats treated with SJW was higher than that of controls. In conclusion, coadministration of SJW significantly increased the systemic exposure and toxicity of MTX. The combined use of MTX with SJW would need to be with caution. -- Highlights: ► St. John's wort significantly increased the AUC{sub 0−t} and C{sub max} of methotrexate. ► Coadministration of St. John's wort increased the exposure and toxicity of methotrexate. ► The combined use of methotrexate with St. John's wort will need to be with caution.

Enhanced and Selective Antiproliferative Activity of Methotrexate-Functionalized-Nanocapsules to Human Breast Cancer Cells (MCF-7

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Catiúscia P. de Oliveira

2018-01-01

Full Text Available Methotrexate is a folic acid antagonist and its incorporation into nanoformulations is a promising strategy to increase the drug antiproliferative effect on human breast cancer cells by overexpressing folate receptors. To evaluate the efficiency and selectivity of nanoformulations containing methotrexate and its diethyl ester derivative, using two mechanisms of drug incorporation (encapsulation and surface functionalization in the in vitro cellular uptake and antiproliferative activity in non-tumoral immortalized human keratinocytes (HaCaT and in human breast carcinoma cells (MCF-7. Methotrexate and its diethyl ester derivative were incorporated into multiwall lipid-core nanocapsules with hydrodynamic diameters lower than 160 nm and higher drug incorporation efficiency. The nanoformulations were applied to semiconfluent HaCaT or MCF-7 cells. After 24 h, the nanocapsules were internalized into HaCaT and MCF-7 cells; however, no significant difference was observed between the nanoformulations in HaCaT (low expression of folate receptors, while they showed significantly higher cellular uptakes than the blank-nanoformulation in MCF-7, which was the highest uptakes observed for the drug functionalized-nanocapsules. No antiproliferative activity was observed in HaCaT culture, whereas drug-containing nanoformulations showed antiproliferative activity against MCF-7 cells. The effect was higher for drug-surface functionalized nanocapsules. In conclusion, methotrexate-functionalized-nanocapsules showed enhanced and selective antiproliferative activity to human breast cancer cells (MCF-7 being promising products for further in vivo pre-clinical evaluations.

Childhood Acute Myeloid Leukemia Treatment (PDQ®)—Health Professional Version

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Acute myeloid leukemia (AML), juvenile myelomonocytic leukemia (JMML), acute promyelocytic leukemia (APL) and chronic myeloid leukemia (CML) account for about 20% of childhood myeloid leukemias. Other myeloid malignancies include transient abnormal myelopoiesis and myelodysplastic syndrome. Get detailed information about the classification, clinical presentation, diagnostic and molecular evaluation, prognosis, and treatment of newly diagnosed and recurrent disease in this summary for clinicians.

Group vs. Individual Treatment for Acute Insomnia: A Pilot Study Evaluating a “One-Shot” Treatment Strategy

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Pam Boullin

2016-12-01

Full Text Available Background: Despite undeniable evidence for the efficacy and effectiveness of Cognitive Behaviour Therapy for Insomnia (CBT-I, the potential for its widespread dissemination and implementation has yet to be realised. A suggested reason for this is that traditional CBT-I is considered too burdensome for deployment, in its current form, within the context of where it would be most beneficial—Primary Care. One strategy, aimed to address this, has been to develop briefer versions of CBT-I, whilst another has been to deliver CBT-I in a group format. An alternative has been to attempt to address insomnia during its acute phase with a view to circumventing its progression to chronic insomnia. The aim of the present study was to compare a brief version of CBT-I (one-shot when delivered individually or in groups to those with acute insomnia. Method: Twenty-eight individuals with acute insomnia (i.e., meeting full DSM-5 criteria for insomnia disorder for less than three months self-assigned to either a group or individual treatment arm. Treatment consisted of a single one-hour session accompanied by a self-help pamphlet. Subjects completed measures of insomnia severity, anxiety and depression pre-treatment and at one-month post-treatment. Additionally, daily sleep diaries were compared between pre-treatment and at the one-month follow up. Results: There were no significant between group differences in treatment outcome on any sleep or mood measures although those in the group treatment arm were less adherent than those who received individual treatment. Furthermore, the combined (group and individual treatment arms pre-post test effect size on insomnia symptoms, using the Insomnia Severity Index, was large (d = 2.27. Discussion: It appears that group treatment is as efficacious as individual treatment within the context of a “one shot” intervention for individuals with acute insomnia. The results are discussed with a view to integrating one-shot CBT

Methotrexate and Cytarabine—Loaded Nanocarriers for Multidrug Cancer Therapy. Spectroscopic Study

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Danuta Pentak

2016-12-01

Full Text Available Determining the properties of nanoparticles obtained by novel methods and defining the scope of their application as drug carriers has important practical significance. This article presents the pioneering studies concerning high degree incorporation of cytarabine (AraC and methotrexate (MTX into liposome vesicles. The main focus of this study were cytarabine-methotrexate-dipalmitoylphosphatidylcholine (DPPC interactions observed in the gel and fluid phases of DPPC bilayers. The proposed new method of use the Transmittance2919/2850 ratio presented in our research is sensitive to subtle changes in conformational order resulting from rotations, kinks and bends of the lipid chains. The transition temperatures characterized by Fourier Transform Infrared Spectroscopy (FT-IR were consistent with the results obtained by Differential Scanning Calorimetry (DSC. Transmission Electron Microscopy (TEM was used in order to determine the size and shape of the liposomes obtained. The mutual interactions occurring between the drugs studied and the phospholipids were analyzed using the Nuclear Magnetic Resonance (NMR.

Structural comparison of complexes of methotrexate analogues with Lactobacillus casei dihydrofolate reductase by two-dimensional 1H NMR at 500 MHz

International Nuclear Information System (INIS)

Hammond, S.J.; Birdsall, B.; Feeney, J.; Searle, M.S.; Roberts, G.C.K.; Cheung, H.T.A.

1987-01-01

The authors have used two-dimensional (2D) NMR methods to examine complexes of Lactobacillus casei dihydrofolate reductase and methotrexate (MTX) analogues having structural modifications of the benzoyl ring and also the glutamic acid moiety. Assignments of the 1 H signals in the spectra of the various complexes were made by comparison of their 2D spectra with those complexes containing methotrexate where we have previously assigned resonances from 32 of the 162 amino acid residues. In the complexes formed with the dihalomethotrexate analogues, the glutamic acid and pteridine ring moieties were shown to bind to the enzyme in a manner similar to that found in the methotrexate-enzyme complex. Perturbations in 1 H chemical shifts of protons in Phe-49, Leu-54, and Leu-27 and the methotrexate H7 and NMe protons were observed in the different complexes and were accounted for by changes in orientation of the benzoyl ring in the various complexes. Binding of oxidized or reduced coenzyme to the binary complexes did not result in different shifts for Leu-27, Leu-54, or Leu-19 protons, and thus, the orientation of the benzoyl ring of the methotrexate analogues is not perturbed greatly by the presence of either oxidized or reduced coenzyme. In the complex with the γ-monoamide analog, the 1 H signals of assigned residues in the protein had almost identical shifts with the corresponding protons in the methotrexate-enzyme complex for all residues except His-28 and, to a lesser extent, Leu-27. This indicates that while the His-28 interaction with the MTX γ-CO 2 - is no longer present in this complex with the γ-amide, there has not been a major change in the overall structure of the two complexes. This behavior contrasts to that of the α-amide complex where 1 H signals from protons in several amino acid residues are different compared with their values in the complex formed with methotrexate

Effects of different forms of central nervous system prophylaxis on neuropsychologic function in childhood leukemia

International Nuclear Information System (INIS)

Rowland, J.H.; Glidewell, O.J.; Sibley, R.F.

1984-01-01

A comparison of the late effects on intellectual and neuropsychologic function of three different CNS prophylaxis regimens was conducted in 104 patients treated for childhood acute lymphocytic leukemia. Of the children studied, 33 were randomized to treatment with intrathecal (IT) methotrexate alone, 36 to IT methotrexate plus 2,400 rad cranial irradiation, and 35 to IT methotrexate plus intravenous intermediate dose methotrexate. All patients were in their first (complete) continuous remission, were a minimum of one year post-CNS prophylaxis and had no evidence of CNS disease at the time of evaluation. In contrast to the other two treatment groups, children whose CNS prophylaxis included cranial irradiation attained significantly lower mean Full Scale IQs, performed more poorly on the Wide Range Achievement Test, a measure of school abilities, and exhibited a greater number of difficulties on a variety of other neuropsychologic measures. The poorer performance of the irradiated group was independent of sex of the patient, time since treatment and age at diagnosis. These data suggest that the addition of 2,400 rad cranial irradiation to CNS prophylaxis in ALL puts these children at greater risk for mild global loss in intellectual and neuropsychologic ability

76 FR 39883 - Design of Clinical Trials for Systemic Antibacterial Drugs for the Treatment of Acute Otitis...

Science.gov (United States)

2011-07-07

...] Design of Clinical Trials for Systemic Antibacterial Drugs for the Treatment of Acute Otitis Media... Clinical Trials for Systemic Antibacterial Agents for the Treatment of Acute Otitis Media. This public... the treatment of acute otitis media (middle ear infection). Discussions will focus on [[Page 39884...

Effect of methotrexate combined with ginger, silymarin or propolis on ...

African Journals Online (AJOL)

The present study was performed to evaluate the effect of three natural antioxidants on the adverse effect of methotrexate (MTX) in normal liver cells. TaqMan RT-PCR technology was used to estimate the mRNA expression levels for three genes after rats injection with a single dose of 20 mg/kg b.w MTX or the same MTX ...

Case Report of Acute Traumatic Rotator Cuff Tear Treatment in Traditional Korean Medicine

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Jeong-Hwan Lee

2011-12-01

Full Text Available Objectives: There is no report on treatment of acute traumatic rotator cuff tear in Traditional Korean Medicine. We reported Traditional Korean Treatment for pain relief and better movement of acute traumatic rotator cuff tear. Methods: Shoulder MRI was used to confirm the diagnosis of tear of rotator cuff. The patient was treated with Traditional Korean Methods (Acupuncture, Herbal medicine, Pharmacopuncture for 6 months. We evaluated the patient through VAS (Visual Analogue Scale, UCLA shoulder scale, ROM (Range of motion and Shoulder MRI. Results: After 6 months of treatment, the patient's VAS was decreased whereas UCLA score and Shoulder ROM were increased. Rotator cuff tear was repaired on Shoulder MRI images. Conclusions: In acute traumatic rotator cuff tear, Korean Traditional Treatment is good method for pain relief and better movement.

Immunosuppressive therapy in non-infections uveitis and retinovasculitis

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E. A. Drozdova

2014-07-01

Full Text Available Purpose: to evaluate the efficacy and safety of the immunosuppressive therapy for severe forms of non-infections uveitis and retinovasculitis.Methods: 107 patients (62 males and 45 females aged 9 to 54 years who received low dose methotrexate — 7.5-20 mg once a week (n=79 cyclosporine A 3.5-5.0 mg/kg/d (n=21 with prednisone or other antimetabolites and local corticosteroid therapy for severe forms of inflammatory eye diseases.Results: the efficacy of methotrexate as monotherapy was 51.8% of patients with chronic uveitis. Control of acute inflammation was achived in 71.1% patients, who received methotrexate in combination with prednisolone. Cyclosporine A was more effective in controlling inflammatory of the eye: remission of uveitis was achived in 85.7% in combination with glucocorticoids. No significant side effects have been noted.Conclusion: Methotrexate and cyclosporine A with low dose of prednisolone are well tolerated immunosuppressive agents andrather effective in the treatment of non-infectious uveitis and retinovasculitis that fails to respond to conventional steroid treatment.

Immunosuppressive therapy in non-infections uveitis and retinovasculitis

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E. A. Drozdova

2012-01-01

Full Text Available Purpose: to evaluate the efficacy and safety of the immunosuppressive therapy for severe forms of non-infections uveitis and retinovasculitis.Methods: 107 patients (62 males and 45 females aged 9 to 54 years who received low dose methotrexate — 7.5-20 mg once a week (n=79 cyclosporine A 3.5-5.0 mg/kg/d (n=21 with prednisone or other antimetabolites and local corticosteroid therapy for severe forms of inflammatory eye diseases.Results: the efficacy of methotrexate as monotherapy was 51.8% of patients with chronic uveitis. Control of acute inflammation was achived in 71.1% patients, who received methotrexate in combination with prednisolone. Cyclosporine A was more effective in controlling inflammatory of the eye: remission of uveitis was achived in 85.7% in combination with glucocorticoids. No significant side effects have been noted.Conclusion: Methotrexate and cyclosporine A with low dose of prednisolone are well tolerated immunosuppressive agents andrather effective in the treatment of non-infectious uveitis and retinovasculitis that fails to respond to conventional steroid treatment.

Hand bone loss in early rheumatoid arthritis during a methotrexate-based treat-to-target strategy with or without adalimumab-a substudy of the optimized treatment algorithm in early RA (OPERA) trial

DEFF Research Database (Denmark)

Ørnbjerg, L M; Østergaard, M; Jensen, T

2017-01-01

This study aims to investigate 1-year hand bone loss (HBL1-year) in early rheumatoid arthritis (RA) patients treated with a methotrexate (MTX) and intra-articular triamcinolone treat-to-target strategy +/- adalimumab and to determine if HBL6months is associated with radiographic progression after 2...... associated with ∆TSS after 2 years (β = -0.086 (95% confidence interval = -0.15; -0.025) TSS unit/mg/cm(2) increase, p = 0.006) but not with presence of radiographic progression (∆TSS >0) (OR 0.96 (0.92-1.0), p = 0.10). In early RA patients treated with a methotrexate-based treat-to-target strategy...

BET 2: LASER THERAPY IN THE TREATMENT OF ACUTE HAMSTRING MUSCLE INJURIES.

Science.gov (United States)

Hughes, Tom; Callaghan, Michael

2017-04-01

Local laser therapy has been suggested as a promising treatment for acute hamstring muscle tears. We carried out a shortcut systematic review to establish whether therapeutic lasers are beneficial for patients with acute hamstring tears. Despite a comprehensive literature search, no studies that were directly relevant to the question could be identified. The clinical bottom line is therefore that there is currently no evidence for the use of any form of laser therapy in the treatment of acute hamstring muscle tears. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

USE OF IMMUNOMODULATORS IN ACUTE RESPIRATORY INFECTION TREATMENT IN FREQUENTLY ILL CHILDREN

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M.I. Ivardava

2011-01-01

Full Text Available Respiratory infections, relapses of ear, nose, throat infections, acute and chronic bronchial infections — these are the most common infantile infections. Regardless the wide range of medications, treatment of recurrent ENT and respiratory infections is not always effective especially in the group of frequently ill children. This article contains analysis of the necessity of immunomodulation therapy of recurrent respiratory infections as a part of complex prophylaxis and treatment of infants.Key words: children, acute respiratory infection, polyoxidonium, treatment.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2011; 10 (3: 103–107

Chiropractic Treatment vs Self-Management in Patients With Acute Chest Pain: A Randomized Controlled Trial of Patients Without Acute Coronary Syndrome

DEFF Research Database (Denmark)

Stochkendahl, Mette J; Christensen, Henrik W; Vach, Werner

2012-01-01

minimal intervention in patients without acute coronary syndrome but with musculoskeletal chest pain. Results suggest that chiropractic treatment might be useful; but further research in relation to patient selection, standardization of interventions, and identification of potentially active ingredients......OBJECTIVE: The musculoskeletal system is a common but often overlooked cause of chest pain. The purpose of the present study is to evaluate the relative effectiveness of 2 treatment approaches for acute musculoskeletal chest pain: (1) chiropractic treatment that included spinal manipulation and (2......) self-management as an example of minimal intervention. METHODS: In a nonblinded, randomized, controlled trial set at an emergency cardiology department and 4 outpatient chiropractic clinics, 115 consecutive patients with acute chest pain and no clear medical diagnosis at initial presentation were...

Methotrexate-induced Pancytopenia in Two Patients with Renal Dysfunction

OpenAIRE

Yusuf OĞUZ; Tayfun EYİLETEN; Murat KARAMAN; Seyid Ahmet AY; Mahmut İlker YILMAZ

2011-01-01

Methotrexate (MTX) is cleared primarily by renal excretion. The excretion of MTX is delayed in subjects with renal dysfunction and elevated plasma MTX concentrations develop which lead to bone marrow toxicities and possible pancytopenia. In this case report, we presented two advanced age patients with MTX-induced pancytopenia. The first patient on hemodialysis was diagnosed with seronegative arthritis while the second patient with congestive heart failure was diagnosed with rheumatoid arthrit...

Life-threatening interaction between the root extract of Pueraria lobata and methotrexate in rats

International Nuclear Information System (INIS)

Chiang, H.-M.; Fang, S.-H.; Wen, K.-C.; Hsiu, S.-L.; Tsai, Shang-Yuan; Hou, Y.-C.; Chi, Y.-C.; Lee Chao, Pei-Dawn

2005-01-01

Isoflavone supplements are nowadays widely used as alternative for hormone replacement therapy. However, the safety remains unanswered. This study attempted to investigate the effect of Pueraria lobata root decoction (PLRD), an isoflavone-rich herb, on the pharmacokinetics of methotrexate (MTX), a bicarboxylate antimetabolite with narrow therapeutic window. Rats were orally and intravenously given methotrexate alone and coadministered with PLRD. Blood samples were withdrawn via cardiopuncture at specific time points after drug administration. Serum methotrexate concentrations were assayed by specific monoclonal fluorescence polarization immunoassay method. Pharmacokinetic parameters were calculated using noncompartment model of WINNONLIN for both oral and intravenous data of MTX. Our results showed that coadministration of 4.0 g/kg and 2.0 g/kg of PLRD significantly increased the AUC 0-t by 207.8% and 127.9%, prolonged the mean residence time (MRT) by 237.8 and 155.2%, respectively, finally resulted in surprisingly high mortalities of 57.1% and 14.3% in rats. When MTX was given intravenously, the coadministration of PLRD at 4.0 g/kg significantly increased the half-life by 53.9% and decreased the clearance by 47.9%. In conclusion, the coadministration of PLRD significantly decreased the elimination and resulted in markedly increased exposure of MTX in rats

Total glucosides of paeony can reduce the hepatotoxicity caused by Methotrexate and Leflunomide combination treatment of active rheumatoid arthritis.

Science.gov (United States)

Xiang, Nan; Li, Xiao-Mei; Zhang, Miao-Jia; Zhao, Dong-Bao; Zhu, Ping; Zuo, Xiao-Xia; Yang, Min; Su, Yin; Li, Zhan-Guo; Chen, Zhu; Li, Xiang-Pei

2015-09-01

Total glucosides of paeony (TGP) have been confirmed to exert anti-inflammatory and hepatoprotective effects. Methotrexate (MTX) and Leflunomide (LEF) combination has a better efficacy in the treatment of active rheumatoid arthritis (RA), but hepatotoxicity was observed. In this study, we investigated the effect of TGP on hepatic dysfunction caused by MTX and LEF in patients with active RA. A total of 268 patients with active RA (disease activity score in 28 joints, DAS28>3.2) were enrolled in this study. All patients were randomly assigned to two groups, the therapeutic group in which patients were treated with TGP (1.8 g/day) combined with MTX and LEF (MTX 10mg/week plus LEF 20mg/day) while in the control group, patients were treated without TGP up to 12 weeks. The efficacy and liver abnormalities were observed. The incidence of abnormal liver function within 12 weeks in TGP group was significantly lower than that in control group (11.38% vs 23.26%, P=0.013). The proportion of patients with ALT/AST >3 times ULN (upper limits of normal) was significantly lower in TGP group than control group (1.63% vs 7.75%, P=0.022). More patients achieved remission, good and moderate response in TGP group than control group at 4, 8 and 12 weeks, but the difference was not significant (P>0.05). The proportions of all adverse events were comparable in the two groups except for diarrhea. Our study demonstrates that TGP can significantly reduce the incidence and severity of liver damage caused by MTX+LEF in the treatment of active RA patients. Copyright © 2015 Elsevier B.V. All rights reserved.

Neurodevelopmental Sequelae of Pediatric Acute Lymphoblastic Leukemia and Its Treatment

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Janzen, Laura A.; Spiegler, Brenda J.

2008-01-01

This review will describe the neurocognitive outcomes associated with pediatric acute lymphoblastic leukemia (ALL) and its treatment. The literature is reviewed with the aim of addressing methodological issues, treatment factors, risks and moderators, special populations, relationship to neuroimaging findings, and directions for future research.…

Childhood Acute Myeloid Leukemia Treatment (PDQ®)—Patient Version

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Childhood acute myeloid leukemia and other myeloid malignancies treatment may include chemotherapy, radiation therapy, stem cell transplant, and targeted therapy. Learn more about AML and myelodysplastic/myeloproliferative diseases in this expert-reviewed summary.

Reduced hepatotoxicity by total glucosides of paeony in combination treatment with leflunomide and methotrexate for patients with active rheumatoid arthritis.

Science.gov (United States)

Chen, Zhu; Li, Xiang-Pei; Li, Zhi-Jun; Xu, Liang; Li, Xiao-Mei

2013-03-01

Combination use of methotrexate (MTX) and leflunomide (LEF) has been proved effective in the treatment of active rheumatoid arthritis (RA). However, previous trials have documented that both are associated with increased incidence of liver toxicity. As active compounds extracted from the roots of the traditional Chinese herb Paeonia lactiflora Pall, total glucosides of paeony (TGP) have been shown to have anti-inflammatory, hepatoprotective and immuno-regulatory activities, without evident toxicity or side effects. In this 24-week, open label, randomized multicenter clinical trial, we investigated the efficacy of TGP and the protective effect on hepatotoxicity in the combination treatment with LEF and MTX for patients with active RA. A total of 204 patients with active RA (DAS28>3.2) recruited from 3 regional referral centers were enrolled and received MTX and LEF combination therapy (MTX 10 mg/week plus LEF 20 mg/day) with or without TGP for up to 24 weeks by randomization. Hepatotoxicity was defined as an increase of at least 1.5-fold the upper limits of normal (ULN) of alanine aminotransferase (ALT) or aspartate aminotransferase (AST). Significantly less frequent hepatotoxicity was observed in patients with TGP than those without (9.5% vs 34.8%, p 1.5 to ≤2 times and >2 to ≤3 times the ULN were lower in TGP group than the control (1.9% vs 10.1%, 2.9% vs 12.4%, p TGP group achieved a European League Against Rheumatism (EULAR) good response or moderate response at 12 weeks, although there is no statistical significance. Similar results were observed at 24 weeks. Our preliminary study demonstrates the hepatoprotective and additive role of TGP in combination with MTX and LEF in the treatment of active RA. Copyright © 2013 Elsevier B.V. All rights reserved.

Minocycline treatment in acute stroke: an open-label, evaluator-blinded study.

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Lampl, Y; Boaz, M; Gilad, R; Lorberboym, M; Dabby, R; Rapoport, A; Anca-Hershkowitz, M; Sadeh, M

2007-10-02

Ischemic animal model studies have shown a neuroprotective effect of minocycline. To analyze the effect of minocycline treatment in human acute ischemic stroke. We performed an open-label, evaluator-blinded study. Minocycline at a dosage of 200 mg was administered orally for 5 days. The therapeutic window of time was 6 to 24 hours after onset of stroke. Data from NIH Stroke Scale (NIHSS), modified Rankin Scale (mRS), and Barthel Index (BI) were evaluated. The primary objective was to compare changes from baseline to day 90 in NIHSS in the minocycline group vs placebo. One hundred fifty-two patients were included in the study. Seventy-four patients received minocycline treatment, and 77 received placebo. NIHSS and mRS were significantly lower and BI scores were significantly higher in minocycline-treated patients. This pattern was already apparent on day 7 and day 30 of follow-up. Deaths, myocardial infarctions, recurrent strokes, and hemorrhagic transformations during follow-up did not differ by treatment group. Patients with acute stroke had significantly better outcome with minocycline treatment compared with placebo. The findings suggest a potential benefit of minocycline in acute ischemic stroke.

Laparoscopic appendectomy in surgical treatment of acute appendicitis

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G. I. Ohrimenko

2016-06-01

Full Text Available Relevance of the topic. At the present time laparoscopic appendectomy has taken its own place at the urgent surgery. In spite of this less is studied in the field of the use of the minimally invasive technologies in the cases of complicated acute appendicitis. The aim of research: to investigate the close results of the patients with acute appendicitis treatment with laparoscopic appendectomy, and to compare them with the open appendectomy results; to estimate the possibilities of laparoscopic appendectomy in the cases of complicated acute appendicitis. Materials and methods. The results of surgical treatment of 146 patients with acute appendicitis were analyzed – 59 patients in the main group, who undergone laparoscopic appendectomy, and 80 patients in the control group, who undergone open surgery. 7 patients who passed through conversion were included in the additional group. Results. The frequency of acute appendicitis complications, which were diagnosed during the operation, in the both groups had no significant distinction (50.8 % in the main group and 47.5% in the control group. But 5 patients with diffuse peritonitis and appendicular abscesses needed a conversion of laparoscopic operation into open one, because of the full sanitation necessity and technique difficulties. In the postoperative period among the patients of main group the suppuration of the wound was observed in 2 (3.4% cases, in the control group – in 10 (12.5%. The average duration of laparoscopic operation was 33.12±2.51 min, open surgery – 66.45±3.33 min. The average hospitalization period in the control group was 6.95±0.2 days and was statistically proved higher than in the main group – 4.72±0.21 days (p≤0.01. Conclusion. Laparoscopic appendectomy can be wide used in the cases of acute appendicitis, including complications, but it can be restricted in the cases of diffuse peritonitis and appendicular abscesses. This minimally invasive surgical operation

Voltammetric Behavior of Methotrexate Using Mercury Meniscus Modified Silver Solid Amalgam Electrode

Czech Academy of Sciences Publication Activity Database

Šelešovská, R.; Bandžuchová, L.; Navrátil, Tomáš

2011-01-01

Roč. 23, č. 1 (2011), s. 177-178 ISSN 1040-0397 R&D Projects: GA AV ČR IAA400400806 Institutional research plan: CEZ:AV0Z40400503 Keywords : methotrexate * voltammetry * determination Subject RIV: CG - Electrochemistry Impact factor: 2.872, year: 2011

Co-association of methotrexate and SPIONs into anti-CD64 antibody-conjugated PLGA nanoparticles for theranostic application

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Moura CC

2014-10-01

Full Text Available Catarina Costa Moura,1,2 Marcela A Segundo,1 José das Neves,3,4 Salette Reis,1 Bruno Sarmento3,4 1REQUIMTE, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal; 2Faculty of Engineering, University of Porto, Porto, Portugal; 3CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Instituto de Ciências da Saúde-Norte, Gandra PRD, Portugal; 4INEB – Instituto de Engenharia Biomédica, University of Porto, Porto, Portugal Background: Rheumatoid arthritis (RA is an autoimmune disease with severe consequences for the quality of life of sufferers. Regrettably, the inflammatory process involved remains unclear, and finding successful therapies as well as new means for its early diagnosis have proved to be daunting tasks. As macrophages are strongly associated with RA inflammation, effective diagnosis and therapy may encompass the ability to target these cells. In this work, a new approach for targeted therapy and imaging of RA was developed based on the use of multifunctional polymeric nanoparticles. Methods: Poly(lactic-co-glycolic acid nanoparticles were prepared using a single emulsion-evaporation method and comprised the co-association of superparamagnetic iron oxide nanoparticles (SPIONs and methotrexate. The nanoparticles were further functionalized with an antibody against the macrophage-specific receptor, CD64, which is overexpressed at sites of RA. The devised nanoparticles were characterized for mean particle size, polydispersity index, zeta potential, and morphology, as well as the association of SPIONs, methotrexate, and the anti-CD64 antibody. Lastly, the cytotoxicity of the developed nanoparticles was assessed in RAW 264.7 cells using standard MTT and LDH assays.Results: The nanoparticles had a mean diameter in the range of 130–200 nm and zeta potential values ranging from -32 mV to -16 mV. Association with either methotrexate or SPIONs did not

Cost analysis of biologic drugs in rheumatoid arthritis first line treatment after methotrexate failure according to patients' body weight.

Science.gov (United States)

Román Ivorra, José Andrés; Ivorra, José; Monte-Boquet, Emilio; Canal, Cristina; Oyagüez, Itziar; Gómez-Barrera, Manuel

2016-01-01

The objective was to assess the influence of patients' weight in the cost of rheumatoid arthritis treatment with biologic drugs used in first line after non-adequate response to methotrexate. Pharmaceutical and administration costs were calculated in two scenarios: non-optimization and optimization of intravenous (IV) vials. The retrospective analysis of 66 patients from a Spanish 1,000 beds-hospital Rheumatology Clinic Service was used to obtain posology and weight data. The study time horizon was two years. Costs were expressed in 2013 euros. For an average 69kg-weighted patient the lowest cost corresponded to abatacept subcutaneous (SC ABA) (€21,028.09) in the scenario without IV vials optimization and infliximab (IFX) (€20,779.29) with optimization. Considering patients' weight in the scenario without IV vials optimization infliximab (IFX) was the least expensive drug in patients ranged 45-49kg, IV ABA in 50-59kg and SC ABA in patients over 60kg. With IV vials optimization IFX was the least expensive drug in patients under 69kg and SC ABA over 70kg. Assuming comparable effectiveness of biological drugs, patient's weight is a variable to consider, potentials savings could reach €20,000 in two years. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Classification system for acute and chronic radiation treatment sequelae

International Nuclear Information System (INIS)

Seegenschmiedt, M.H.; Sauer, R.

1993-01-01

A classification system in German language is proposed for scoring of acute and chronic treatment sequelae after radiotherapy. It includes all important organs and organ systems. The proposed grading corresponds to the four-scale-system of the WHO and UICC. The system is also compatible to the RTOG and EORTC acute and late radiation morbidity scoring criteria. This facilitates the data transfer for retrospective and prospective analysis of monomodal and multimodal radiotherapy treatment regimes. We recommend to use this scoring system in all German speaking countries for multicentric prospective studies. It is possible, that organ-specific sophistications of the toxicity grading will be developed in the future. These additions should conform with (inter)national standards and apply the same four-scale grading of this classification system. (orig.) [de

Tofacitinib, an oral Janus kinase inhibitor, as monotherapy or with background methotrexate, in Japanese patients with rheumatoid arthritis: an open-label, long-term extension study.

Science.gov (United States)

Yamanaka, Hisashi; Tanaka, Yoshiya; Takeuchi, Tsutomu; Sugiyama, Naonobu; Yuasa, Hirotoshi; Toyoizumi, Shigeyuki; Morishima, Yosuke; Hirose, Tomohiro; Zwillich, Samuel

2016-01-28

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. Here, tofacitinib safety and efficacy data from a long-term extension study in Japanese patients are presented. Study A3921041 was a multi-centre, open-label, long-term extension study that included Japanese patients who had participated in a prior Phase 2 or Phase 3 study of tofacitinib as monotherapy or with background methotrexate. Patients received tofacitinib 5 mg twice daily (BID) or tofacitinib 10 mg BID. Dose adjustment of tofacitinib during treatment period, and concomitant usage of disease-modifying antirheumatic drugs including methotrexate after week 12 were permitted. Primary endpoints were adverse events, laboratory parameters and vital signs. Secondary efficacy endpoints included American College of Rheumatology (ACR)20/50/70 response rates, Disease Activity Score (DAS)28-4(erythrocyte sedimentation rate (ESR))tofacitinib-treated patients, the incidence rate (patients with events per 100 patient-years) was 10.7 for serious adverse events, 3.3 for serious infections, 7.4 for herpes zoster (serious and non-serious) and 1.2 for malignancies (excluding non-melanoma skin cancer). Mean changes from baseline (start of the index study) in laboratory parameters were consistent with those seen in previously reported studies of tofacitinib. ACR20/50/70 response rates, DAS-defined remission rates and HAQ-DI scores were sustained through to study completion. Tofacitinib (with or without background methotrexate) demonstrated a stable safety profile and sustained efficacy in Japanese patients with active rheumatoid arthritis. The risk of herpes zoster appears to be higher in Japanese patients treated with tofacitinib than in the global population. Clinicaltrials.gov NCT00661661 . Registered 7 February 2008.

Índice orientador do tratamento sistêmico da gravidez ectópica íntegra com dose única de metotrexato Index for the systemic treatment of unruptured ectopic pregnancy with a single dose of methotrexate

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Julio Elito Junior

1998-04-01

iguais a cinco estiveram todas relacionadas com o fracasso do tratamento. O índice orientador ajuda-nos a indicar os melhores casos para o tratamento medicamentoso. Não o aconselhamos, portanto, quando a nota for inferior ou igual a cinco; por outro lado, podemos predizer boa evolução do tratamento, quando a nota for superior a cinco.A prospective study was performed with 42 patients with unruptured ectopic pregnancy, which intended to elaborate an index to orient the systemic treatment with the administration of a single intramuscular dose of methotrexate (50 mg/m². Patients were monitored with beta-hCG titers on days 1, 4 and 7 after the methotrexate. When the titers of beta-hCG declined more than 15%, between days 4 and 7 after methotrexate, the patients were discharged and had an outpatient follow-up monitored with beta-hCG titers weekly until the titers were less than 5 mIU/ml, which represents success of the treatment. We prepared an index for the systemic treatment with methotrexate, with five parameters: (1 initial titers of beta-hCG; (2 aspects of the image at ultrasound (hematosalpinx, gestational sac, live embryo; (3 size of the mass; (4 free fluid in cul-de-sac; (5 collor doppler. Each parameter received a grade from 0 to 2. Grade 0 represented bad prognosis, favorable parameters received grade 2 and borderline parameters received grade one. The success rate with a single dose of methotrexate was 69.0% (29/42. The color doppler was performed in 20 of the 42 patients; in this group of 20 patients the success rate was 75.0% (15/20. In the 22 patients who were not submitted to the color doppler, the average grade of the score in the successful cases was 6.6, and in the unsuccessful it was 3.1. In the group who underwent the doppler (20 patients the average was 7.9 in the successful cases and 4.2 in the cases that failed. In the present study the cut-off grade was 5, for most of the patients with grades above 5 had a successful treatment (15/16 - 93

An improvement of the child acute respiratory infection treatment program

OpenAIRE

E. N. Simovan'yan; E. E. Badalyants; L. P. Sizyakina; A. A. Lebedenko; V. B. Denisenko; M. A. Kim

2013-01-01

High morbidity rate, frequent development of severe complication forms, unfavorable remote effects for children’s health, insufficient efficacy of the used acute respiratory infection therapy schemes necessitate a treatment program improvement for this group of diseases. A complex clinical-laboratory examination of 72 3-6-year-old children with acute nasopharyngites and bronchites was conducted. Dependence of the disease’s clinical form and course peculiarities from the premorbid setting stat...

Reinduction therapy for adult acute leukemia with adriamycin, vincristine, and prednisone: a Southwest Oncology Group study.

Science.gov (United States)

Elias, L; Shaw, M T; Raab, S O

1979-08-01

In an attempt to improve remissions and survivals in previously treated patients with adult acute leukemia, we gave Adriamycin, vincristine, and prednisone for induction therapy, followed by 6-mercaptopurine and methotrexate for maintenance therapy to patients attaining complete remission (CR). The study group consisted of 18 patients with acute myeloblastic leukemia (AML), ten with acute lymphoblastic leukemia, and one with acute undifferentiated leukemia. Only one patient had previously received Adriamycin. Overall, there were ten CRs and two partial remissions. The five CRs and one partial remission in patients with AML occurred among those with one prior induction attempt; none of the eight AML patients with more than one prior induction attempt responded. The actuarial median duration of CR was 15 weeks and was similar for AML and acute lymphoblastic leukemia patients. Responders had a longer median survival (30 weeks) than nonresponders (9 weeks). Thus, although a reasonable number of responses in previously treated patients were obtained with this program, improvements in maintenance therapy are clearly needed.

Assessment by MRI of inflammation and damage in rheumatoid arthritis patients with methotrexate inadequate response receiving golimumab: results of the GO-FORWARD trial

DEFF Research Database (Denmark)

Conaghan, Philip G; Emery, Paul; Østergaard, Mikkel

2011-01-01

To evaluate golimumab's effect on MRI-detected inflammation and structural damage in patients with active rheumatoid arthritis (RA) despite methotrexate (MTX).......To evaluate golimumab's effect on MRI-detected inflammation and structural damage in patients with active rheumatoid arthritis (RA) despite methotrexate (MTX)....

Comparison of the therapeutic effects of thymoquinone and methotrexate on renal injury in pristane induced arthritis in rats

International Nuclear Information System (INIS)

Faisal, R.

2015-01-01

To determine the effect of thymoquinone and methotrexate on blood urea and serum creatinine in arthritic rats. Study Design:Experimental, comparative study. Place and Duration of Study: Postgraduate Medical Institute, Lahore, from March to August 2013. Methodology: Thirty two female Sprague-Dawley rats were randomized into four equal groups (n=8); group A(healthy control), group B (positive control), group C (Thymoquinone treated) and group D (Methotrexate treated). Arthritis developed within two weeks after a single pristane injection. Total leukocyte count, blood urea and serum creatinine were taken at day 0, 15 and 30. While clinical score of inflammation was taken at day 0 and then on every alternate day. Results: Development of arthritis and renal involvement was accompanied by significant raise in total leukocyte count, clinical score of inflammation, blood urea and serum creatinine as compared to healthy control rats (group A) till day 15 (p < 0.001). From day 15 to day 30 both thymoquinone (group C) and methotrexate (group D) significantly lowered the total leukocyte count, clinical score of inflammation and improved blood urea and serum creatinine as compared to arthritic rats (group B) (p < 0.001). Methotrexate was found a bit more effective than thymoquinone. Conclusion: Evaluation of results supported the beneficial effects of thymoquinone in renal injury produced by rheumatoid arthritis. (author)

Patient Satisfaction in the Treatment of Acute Hamstring Strain Injury

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LingLing- Lai

2014-05-01

Full Text Available Introduction: The impact of musculoskeletal injuries often caused loss time in sport participation. Athletes who suffered from these injuries experienced a decrease in performance and physical disability. Although a variety of treatments have been implemented to the muscle injuries, the administration of autologous blood injection is replacing the conventional rehabilitation to expedite the process of muscle recovery. Platelet-rich plasma (PRP is relatively new in muscle injury treatment and there is lack of evidence of the satisfaction of PRP treatment in muscle injuries. Purposes: The study aimed to investigate the patient satisfaction in the administration of PRP treatment and rehabilitation program for acute hamstring strain injury. Methods: Participants (competitive, semi-competitive and recreational athletes with acute hamstring strain injury (Grade II were recruited. Participants were randomly divided into either the PRP treatment or rehabilitation program. Participants were required to attend weekly follow up assessment for recovery evaluation. All the participants were required to complete a patient satisfaction questionnaire (PSQ-18 at the end of study.  The questionnaire is divided into seven sub-scales: general satisfaction, technical quality, interpersonal manner, communication, financial aspect, time spent with doctor, accessibility and convenience. Results: Participants were 22.35 ± 3.41 years. Duration from injury to first presentation in clinic ranged from two to ten days. Mean duration of recovery was 5.64 weeks. No statistically significant difference in the patient satisfaction sub-scales score between the two groups (p>0.05. Conclusion: The present study demonstrates that PRP treatment is as satisfactory as conventional rehabilitation program in managing acute hamstring strain injury. Both  modalities are correspondingly safe and have high degree of satisfaction. Given the acceptable outcomes, patients are likely to

Randomized phase III trial (GORTEC 98-03) comparing re-irradiation plus chemotherapy versus methotrexate in patients with recurrent or a second primary head and neck squamous cell carcinoma, treated with a palliative intent

International Nuclear Information System (INIS)

Tortochaux, Jacques; Tao Yungan; Tournay, Elodie; Lapeyre, Michel; Lesaunier, Francois; Bardet, Etienne; Janot, Francois; Lusinchi, Antoine; Benhamou, Ellen; Bontemps, Patrick; Maingon, Philippe; Calais, Gilles; Daly-Schveitzer, Nicolas; Verrelle, Pierre; Bourhis, Jean

2011-01-01

Purpose: This randomized phase III trial investigated the potential benefit of concurrent re-irradiation, fluorouracil and hydroxyurea versus methotrexate for patients treated with palliative intent for recurrent or second primary head and neck squamous cell carcinoma (HNSCC) in previously irradiated area. Patients and methods: Patients with recurrent HNSCC or a second primary not amenable to curative-intent treatment were randomized to the R-RT arm (concurrent re-irradiation, fluorouracil and hydroxyurea) or to the Ch-T arm (methotrexate). The primary endpoint was overall survival (OS). Due to a very slow accrual, the trial was closed after inclusion of 57 patients. Results: Fifty-seven patients were included. All patients died in the two arms with a maximal follow-up of 5 years. Although four complete responses were achieved in R-RT arm, (none in Ch-T arm) re-irradiation did not improve OS compared with methotrexate (23% versus 22% at 1 year, NS). Sixteen patients experienced clinical grade ≥3 late toxicities (>6 months), 11 in R-RT arm and five in Ch-T arm. Conclusions: Premature discontinuation of the trial did not allow us to draw firm conclusions. However, there was no suggestion that concurrent re-irradiation, fluorouracil and hydroxyurea improved OS compared to methotrexate alone in patients treated with palliative intent for a recurrent or second primary HNSCC.

Endovascular treatment of acute arterial complications after living-donor liver transplantation

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Jeon, G.S. [Department of Diagnostic Radiology, Ajou University Hospital, School of Medicine, San 5, Wonchun-dong, Youngtong-gu, Suwon, Gyeonggido 443-721 (Korea, Republic of); Won, J.H. [Department of Diagnostic Radiology, Ajou University Hospital, School of Medicine, San 5, Wonchun-dong, Youngtong-gu, Suwon, Gyeonggido 443-721 (Korea, Republic of)], E-mail: wonkwak@ajou.ac.kr; Wang, H.J.; Kim, B.W. [Department of Surgery, Ajou University Hospital, School of Medicine, San 5, Wonchun-dong, Youngtong-gu, Suwon, Gyeonggido 443-721 (Korea, Republic of); Lee, B.M. [Department of Surgery, Aerospace medical center, Ssangsu-ri, Cheongwon-gun, Chungcheongbuk-do 363-849 (Korea, Republic of)

2008-10-15

Aim: The aim of this study was to evaluate the efficacy of endovascular treatment for acute arterial complications following living-donor liver transplantation (LDLT). Materials and methods: Of 79 LDLT patients, 17 (mean age 48 {+-} 8 years, range 33-66 years) who had acute arterial complications and underwent endovascular treatment were evaluated. Transcatheter arterial embolization was performed to control peritoneal bleeding. Catheter-directed thrombolysis using urokinase was performed in hepatic artery thromboses. The locations of complications and materials used were evaluated. The technical and clinical success rates were calculated. Results: Twenty-three acute arterial complications, including four hepatic artery thromboses and 19 cases of peritoneal haemorrhages were identified in 22 angiographic sessions in 17 patients. The mean duration between LDLT and first angiography was 3.2 {+-} 3.5 days (range 1-13 days). Hepatic artery recanalization with catheter-directed thrombolysis using urokinase was achieved in two patients. Transcatheter arterial embolization for peritoneal bleeding was successfully performed in 16 cases. The most common bleeding focus was the right inferior phrenic artery. Additional surgical management was needed in five patients to control bleeding or hepatic artery recanalization. Technical and clinical success rates of transcatheter arterial embolization were 84.2 and 63.1%, respectively. Overall technical success was achieved in 18 of 23 arterial complications (78.2%), and clinical success was achieved in 14 of 23 arterial complications (60.8%). Conclusion: Endovascular treatment for the acute arterial complications of haemorrhage or thrombosis in LDLT patients is safe and effective. Therefore, it should be considered as the first line of treatment in selective cases.

N-feruloylserotonin in preventive combination therapy with methotrexate reduced inflammation in adjuvant arthritis

Czech Academy of Sciences Publication Activity Database

Kuncírová, V.; Poništ, S.; Mihalová, D.; Dráfi, F.; Nosáľ, R.; Acquaviva, A.; Gardi, C.; Harmatha, Juraj; Hrádková, I.; Bauerová, K.

2014-01-01

Roč. 28, č. 6 (2014), s. 616-626 ISSN 0767-3981 Institutional support: RVO:61388963 Keywords : arthritis * inflammation * oxidative stress * combination therapy * methotrexate * N-feruloylserotonin Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 2.121, year: 2014

Herpes simplex type 2 encephalitis and methotrexate medication: a fortuitous or causative association in a patient with spondyloarthritis?

Science.gov (United States)

Lupo, Julien; Dos Santos, Ophélie; Germi, Raphaele; Baccard-Longère, Monique; Stahl, Jean-Paul; Epaulard, Olivier; Morand, Patrice

2017-01-01

It is unclear whether immunosuppression is a risk factor for herpes encephalitis. Herein, we describe a rare case of herpes simplex virus type 2 encephalitis in a patient treated with low-dose methotrexate for HLA-B27-associated spondyloarthritis. The patient was successfully treated with acyclovir but presented sequelae of encephalitis. Here we discuss the possible role of low-dose methotrexate therapy as a risk factor of neurological herpes reactivation and severe disease. The host-related and viral risk factors are also addressed.

Treatment of hyperglycaemia in patients with acute stroke.

Science.gov (United States)

Castilla-Guerra, L; Fernández-Moreno, M C; Hewitt, J

2016-03-01

The proportion of diabetic patients who are hospitalised for stroke has been increasing in recent years, currently reaching almost a third of all cases of stroke. In addition, about half of patients with acute stroke present hyperglycaemia in the first hours of the stroke. Although hyperglycaemia in the acute phase of stroke is associated with a poor prognosis, its treatment is currently a topic of debate. There is no evidence that the adminstration of intravenous insulin to these patients offers benefits in terms of the evolution of the stroke. New studies in development, such as the SHINE study (Stroke Hyperglycemia Insulin Network Effort), may contribute to clarifying the role of intensive control of glycaemia during the acute phase of the stroke. Ultimately, patients who have presented with stroke should be screened for diabetes. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Intranasal fentanyl in the treatment of acute pain--a systematic review

DEFF Research Database (Denmark)

Hansen, M S; Mathiesen, O; Trautner, S

2012-01-01

Due to its non-invasive mode of administration, intranasal (IN) application of drugs may be a valuable alternative to non-invasive pain management. With characteristics that appear to be ideal for IN application, IN fentanyl may have a place in the out-of-hospital treatment and the paediatric...... population. The objective of this systematic review was to evaluate the current evidence of IN fentanyl in the treatment of acute pain. Reports of randomized controlled trials (RCTs) of IN fentanyl in treatment of pain were systematically sought using the PubMed database, Embase, Google scholar, Cochrane...... database, and Cumulative Index to Nursing and Allied Health Literature. Reports were considered for inclusion if they were double-blinded randomized controlled trials (RCTs) of IN fentanyl in the treatment of acute pain. Thirty-two RCTs were identified, and 16 were included in the final analysis...

Persistent fever during treatment of a pregnant woman with acute pyelonephritis

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Hasan Tahsin Gozdas

2017-01-01

Full Text Available Acute pyelonephritis is a serious infection in pregnancy. It is presented with fever, shaking chills and flank pain. Intravenous hydration and antimicrobial therapy are sufficient in the treatment unless pyelonephritis is complicated. In case of fever persisting for more than 48 h despite appropriate antimicrobial treatment, a possible complication such as urinary tract obstruction, abscess or phlegmon should be considered. Here, we present an 18-year-old pregnant woman with acute pyelonephritis whose persistent fever returned to normal after double-J ureteral stent was placed even if she had no finding of such a complication.

The METEX study: Methotrexate versus expectant management in women with ectopic pregnancy: A randomised controlled trial

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Visser Harry

2008-06-01

Full Text Available Abstract Background Patients with ectopic pregnancy (EP and low serum hCG concentrations and women with a pregnancy of unknown location (PUL and plateauing serum hCG levels are commonly treated with systemic methotrexate (MTX. However, there is no evidence that treatment in these particular subgroups of women is necessary as many of these early EPs may resolve spontaneously. The aim of this study is whether expectant management in women with EP or PUL and with low but plateauing serum hCG concentrations is an alternative to MTX treatment in terms of treatment success, future pregnancy, health related quality of life and costs. Methods/Design A multicentre randomised controlled trial in The Netherlands. Hemodynamically stable patients with an EP visible on transvaginal ultrasound and a plateauing serum hCG concentration Discussion This trial will provide guidance on the present management dilemmas in women with EPs and PULs with low and plateauing serum hCG concentrations. Trial registration Current Controlled Trials ISRCTN 48210491

Successful Management of Tubal Ectopic Pregnancy with Transvaginal Sonography Guided Intracardiac KCL Injection and Systemic Methotrexate - A Case Report

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Sumesh Choudhary

2014-01-01

Full Text Available Background: Methotrexate (Mtx is an accepted modality for conservative treatment of ectopic pregnancy. However, there is no consensus regarding its use in live ectopic pregnancy and high serum beta-human chorionic gonadotrophin (β-hCG titres. Concurrent use of intra-sac hypertonic KCl, to produce cardiac asystole with systemic Mtx potentially improve outcome in live ectopic gestations with very high serum β-hCG titres. Here a successful management of live ectopic pregnancy in a 25-year-old nulliparous woman, with very high β-hCG titres (29502.04mIU/mL, using ultrasound-guided intra-cardiac potassium chloride (KCl injection and systemic Mtx is reported. No treatment related complications were encountered. However, individualized treatment with a stringent follow-up regime is mandatory in such cases.

Early definitive treatment rate as a quality indicator of care in acute gallstone pancreatitis.

Science.gov (United States)

Green, R; Charman, S C; Palser, T

2017-11-01

Early definitive treatment (cholecystectomy or endoscopic sphincterotomy in the same admission or within 2 weeks after discharge) of gallstone disease after a biliary attack of acute pancreatitis is standard of care. This study investigated whether compliance with early definitive treatment for acute gallstone pancreatitis can be used as a care quality indicator for the condition. A retrospective cohort study was conducted using the Hospital Episode Statistics database. All emergency admissions to National Health Service hospitals in England with a first time diagnosis of acute gallstone pancreatitis in the financial years 2008, 2009 and 2010 were examined. Trends in early definitive treatment between hospital trusts were examined and patient morbidity outcomes were determined. During the study interval there were 19 510 patients with an overall rate of early definitive treatment at 34·7 (range 9·4-84·7) per cent. In the 1-year follow-up period, 4661 patients (23·9 per cent) had one or more emergency readmissions for complications related to gallstone pancreatitis. Of these, 2692 (57·8 per cent) were readmissions for acute pancreatitis; 911 (33·8 per cent) were within the first 2 weeks of discharge, with the remaining 1781 (66·2 per cent) occurring after the point at which definitive treatment should have been received. Early definitive treatment resulted in a 39 per cent reduction in readmission risk (adjusted risk ratio (RR) 0·61, 95 per cent c.i. 0·58 to 0·65). The risk was further reduced for acute pancreatitis readmissions to 54 per cent in the early definitive treatment group (adjusted RR 0·46, 0·42 to 0·51). In acute gallstone pancreatitis, compliance with recommended early definitive treatment varied considerably, with associated variation in outcomes. Compliance should be used as a quality indicator to improve care. © 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.

Nonsteroidal anti-inflammatory drugs for treatment of acute gout

NARCIS (Netherlands)

van Durme, Caroline M. P. G.; Wechalekar, Mihir D.; Landewé, Robert B. M.

2015-01-01

Are nonsteroidal anti-inflammatory drugs (NSAIDs) associated with better outcomes than cyclooxygenase inhibitors, glucocorticoids, IL-1 inhibitors or placebo in the treatment of acute gout? NSAIDs are not significantly associated with a difference in pain reduction compared with cyclooxygenase

Involvement of Multiple Transporters-mediated Transports in Mizoribine and Methotrexate Pharmacokinetics

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Teruo Murakami

2012-08-01

Full Text Available Mizoribine is administered orally and excreted into urine without being metabolized. Many research groups have reported a linear relationship between the dose and peak serum concentration, between the dose and AUC, and between AUC and cumulative urinary excretion of mizoribine. In contrast, a significant interindividual variability, with a small intraindividual variability, in oral bioavailability of mizoribine is also reported. The interindividual variability is mostly considered to be due to the polymophisms of transporter genes. Methotrexate (MTX is administered orally and/or by parenteral routes, depending on the dose. Metabolic enzymes and multiple transporters are involved in the pharmacokinetics of MTX. The oral bioavailability of MTX exhibits a marked interindividual variability and saturation with increase in the dose of MTX, with a small intraindividual variability, where the contribution of gene polymophisms of transporters and enzymes is suggested. Therapeutic drug monitoring of both mizoribine and MTX is expected to improve their clinical efficacy in the treatment of rheumatoid arthritis.

The Best Choice of Treatment for Acute Colonic Diverticulitis with Purulent Peritonitis Is Uncertain

DEFF Research Database (Denmark)

Hupfeld, Line; Burcharth, Jakob; Pommergaard, Hans-Christian

2014-01-01

Severe stages of acute, colonic diverticulitis can progress into intestinal perforations with peritonitis. In such cases, urgent treatment is needed, and Hartmann's procedure is the standard treatment for cases with fecal peritonitis. Peritoneal lavage may be an alternative to resection for acute...... diverticulitis with purulent peritonitis, but ongoing randomized trials are awaited to clarify this....

Treatment of the complex abdomen and acute intestinal failure

NARCIS (Netherlands)

de Vries, F.E.E.

2018-01-01

Management of the complex abdomen and acute intestinal failure (IF) is challenging and requires specialized multidisciplinary treatment. Due to the small numbers and heterogeneity of the patient group high-quality evidence for some of the research questions is probably unachievable. Nevertheless,

Acute appendicitis in children: not only surgical treatment.

Science.gov (United States)

Caruso, Anna Maria; Pane, Alessandro; Garau, Roberto; Atzori, Pietro; Podda, Marcello; Casuccio, Alessandra; Mascia, Luigi

2017-03-01

An accurate diagnosis of acute appendicitis is important to avoid severe outcome or unnecessary surgery but management is controversial. The aim of study was to evaluate, in younger and older children, the efficacy of conservative management for uncomplicated appendicitis and the outcome of complicated forms underwent early surgery. Children with acute appendicitis were investigated by clinical, laboratory variables and abdominal ultrasound and divided in two groups: complicated and uncomplicated. Complicated appendicitis underwent early surgery; uncomplicated appendicitis started conservative treatment with antibiotic. If in the next 24-48h it was worsening, the conservative approach failed and patients underwent late surgery. A total of 362 pediatric patients were included. One hundred sixty-five underwent early appendectomy; 197 patients were at first treated conservatively: of these, 82 were operated within 24-48h for failure. The total percentage of operated patients was 68.2%. An elevated association was found between surgery and ultrasound. Conservative treatment for uncomplicated appendicitis had high percentage of success (58%). Complications in operated patients were infrequent. Our protocol was effective in order to decide which patients treat early surgically and which conservatively; specific red flags (age and onset) can identified patients at most risk of complications or conservative failure. treatment study. II. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparison of efficacy of procedures in the treatment of acute angle-closure glaucoma

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Lian-Rong Su

2013-06-01

Full Text Available AIM: To observe the clinical effects of 3 different surgery treatments for acute angle-closure glaucoma. METHODS: Totally 60 cases of acute angle-closure glaucoma were randomly divided into 3 groups. Iris root excision or laser iridotomy was applied to group A, cataract phacoemulsification with artificial lens implantation and goniosynechialysis for group B, crabeculectomy for group C. The changes of vision, intraocular pressure, chamber angle, anterior chamber depth before and after operation were observed, while the postoperative complications and following operations were analyzed. The period of follow-up was one week, one month, three months and six months.RESULTS: No statistical significance was found for treatments of group A and C(P>0.05. For group C the treatment was statistically significant(PPPCONCLUSION: Cataract phacoemulsification with artificial lens implantation and goniosynechialysis is a safe and effective surgery for treatment of acute angle-closure glaucoma, which can effectively improve vision, decrease intraocular pressure, open anterior chamber angle.

Systemic methotrexate to treat ectopic pregnancy does not affect ovarian reserve.

Science.gov (United States)

Oriol, Bárbara; Barrio, Ana; Pacheco, Alberto; Serna, José; Zuzuarregui, José Luis; Garcia-Velasco, Juan A

2008-11-01

To evaluate whether methotrexate (MTX) compromises ovarian reserve and future reproductive outcome in women undergoing assisted reproductive technology (ART), when it is used as first-line treatment for ectopic pregnancy (EP). Prospective, observational study. University-affiliated private IVF unit. Twenty-five women undergoing IVF-ICSI who were treated with MTX (1 mg/kg IM) for an EP after ART. Evaluation of reproductive outcome and serum anti-Müllerian hormone (AMH) levels. Serum AMH was evaluated before administering MTX and >or=1 week after the resolution of the EP. Reproductive outcome was evaluated by comparing subsequent IVF-ICSI cycles after EP resolution. Serum AMH levels, cycle length, gonadotropin dose required, peak serum E(2) level, oocytes collected, and embryos obtained. Serum AMH levels before MTX were not statistically significantly different from those after treatment (3.7 +/- 0.3 ng/mL vs. 3.9 +/- 0.3 ng/mL). Patients undergoing a subsequent cycle after systemic treatment for EP had similar cycle durations (10.3 vs. 10.8 d), gonadotropin requirements (2,775 vs. 2,630.3 IU), peak E(2) levels (1,884.3 vs. 1,523.6 pg/mL), number of oocytes retrieved (12.1 vs. 10.5), and total number of embryos obtained (7.1 vs. 6.5). Single-dose MTX is a safe first-treatment choice that does not compromise future reproductive outcomes in women who are diagnosed with EP after ART.

Diffusion and Perfusion MR Imaging in Acute Stroke: Clinical Utility and Potential Limitations for Treatment Selection

DEFF Research Database (Denmark)

Bateman, Mathew; Slater, Lee-Anne; Leslie-Mazwi, Thabele M

2017-01-01

Magnetic resonance (MR) diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) offer unique insight into acute ischemic stroke pathophysiology. These techniques may offer the ability to apply pathophysiology to accurately individualize acute stroke reperfusion treatment, including ...... to be investigated in ongoing randomized controlled trials, and continued research into these techniques will help achieve the goal of tissue-based decision making and individualized acute stroke treatment....... extending the opportunity of reperfusion treatment to well beyond the current time-based treatment windows. This review examines the use of DWI and PWI in the major stroke trials, their current clinical utility, and potential limitations for reperfusion treatment selection. DWI and PWI continue...

Diagnosis and treatment of acute low back pain.

Science.gov (United States)

Casazza, Brian A

2012-02-15

Acute low back pain is one of the most common reasons for adults to see a family physician. Although most patients recover quickly with minimal treatment, proper evaluation is imperative to identify rare cases of serious underlying pathology. Certain red flags should prompt aggressive treatment or referral to a spine specialist, whereas others are less concerning. Serious red flags include significant trauma related to age (i.e., injury related to a fall from a height or motor vehicle crash in a young patient, or from a minor fall or heavy lifting in a patient with osteoporosis or possible osteoporosis), major or progressive motor or sensory deficit, new-onset bowel or bladder incontinence or urinary retention, loss of anal sphincter tone, saddle anesthesia, history of cancer metastatic to bone, and suspected spinal infection. Without clinical signs of serious pathology, diagnostic imaging and laboratory testing often are not required. Although there are numerous treatments for nonspecific acute low back pain, most have little evidence of benefit. Patient education and medications such as nonsteroidal anti-inflammatory drugs, acetaminophen, and muscle relaxants are beneficial. Bed rest should be avoided if possible. Exercises directed by a physical therapist, such as the McKenzie method and spine stabilization exercises, may decrease recurrent pain and need for health care services. Spinal manipulation and chiropractic techniques are no more effective than established medical treatments, and adding them to established treatments does not improve outcomes. No substantial benefit has been shown with oral steroids, acupuncture, massage, traction, lumbar supports, or regular exercise programs.

Treatment Algorithms in Systemic Lupus Erythematosus.

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Muangchan, Chayawee; van Vollenhoven, Ronald F; Bernatsky, Sasha R; Smith, C Douglas; Hudson, Marie; Inanç, Murat; Rothfield, Naomi F; Nash, Peter T; Furie, Richard A; Senécal, Jean-Luc; Chandran, Vinod; Burgos-Vargas, Ruben; Ramsey-Goldman, Rosalind; Pope, Janet E

2015-09-01

To establish agreement on systemic lupus erythematosus (SLE) treatment. SLE experts (n = 69) were e-mailed scenarios and indicated preferred treatments. Algorithms were constructed and agreement determined (≥50% respondents indicating ≥70% agreement). Initially, 54% (n = 37) responded suggesting treatment for scenarios; 13 experts rated agreement with scenarios. Fourteen of 16 scenarios had agreement as follows: discoid lupus: first-line therapy was topical agents and hydroxychloroquine and/or glucocorticoids then azathioprine and subsequently mycophenolate (mofetil); uncomplicated cutaneous vasculitis: initial treatment was glucocorticoids ± hydroxychloroquine ± methotrexate, followed by azathioprine or mycophenolate and then cyclophosphamide; arthritis: initial therapy was hydroxychloroquine and/or glucocorticoids, then methotrexate and subsequently rituximab; pericarditis: first-line therapy was nonsteroidal antiinflammatory drugs, then glucocorticoids with/without hydroxychloroquine, then azathioprine, mycophenolate, or methotrexate and finally belimumab or rituximab, and/or a pericardial window; interstitial lung disease/alveolitis: induction was glucocorticoids and mycophenolate or cyclophosphamide, then rituximab or intravenous gamma globulin (IVIG), and maintenance followed with azathioprine or mycophenolate; pulmonary hypertension: glucocorticoids and mycophenolate or cyclophosphamide and an endothelin receptor antagonist were initial therapies, subsequent treatments were phosphodiesterase-5 inhibitors and then prostanoids and rituximab; antiphospholipid antibody syndrome: standard anticoagulation with/without hydroxychloroquine, then a thrombin inhibitor for venous thrombosis, versus adding aspirin or platelet inhibition drugs for arterial events; mononeuritis multiplex and central nervous system vasculitis: first-line therapy was glucocorticoids and cyclophosphamide followed by maintenance with azathioprine or mycophenolate, and

The use of Bioptron light (polarized, polychromatic, non-coherent) therapy for the treatment of acute ankle sprains.

Science.gov (United States)

Stasinopoulos, Dimitrios; Papadopoulos, Costas; Lamnisos, Dimitrios; Stasinopoulos, Ioannis

2017-03-01

Purpose The purpose of this study was to investigate the efficacy of Bioptron light therapy for the treatment of acute ankle sprains. Method A parallel group, single-blind, controlled study was carried out in patients with grade II acute ankle sprains. Patients were randomly allocated into two treatment groups (n = 25 for each). Both groups received cryotherapy, and the test group also received Bioptron light therapy. All treatments were performed daily for 5 d. Evaluations included self-reported pain via a visual analogue scale, degree of ankle edema, and ankle range of motion via goniometry carried out before the treatment and at the end of the treatment. Results The test group showed the largest magnitude of improvement for all evaluations at treatment five, and the between-group differences observed were statistically significant (p Bioptron light therapy supplemented with cryotherapy for the treatment of acute ankle sprains; however, larger studies are required to confirm these results. Implications for Rehabilitation Ankle sprains are common acute injuries among professional and recreational sports players but also among people in general. Cryotherapy is the first-standard treatment of acute ankle sprains. Phototherapy such as Bioptron light has been recommended supplement to cryotherapy to reduce the symptoms of ankle sprains. The results of the present trial showed that using BIOPTRON LIGHT and cryotherapy the rehabilitation period of acute ankle sprains can be reduced.

Prophylaxis and treatment of acute and chronic postherpetic neuralgia

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Anna Michalska-Bańkowska

2014-06-01

Full Text Available Herpes zoster (HZ is a disease caused by varicella zoster virus (VZV, where the initial contact leads to varicella. The low immunity of the patient might reactivate the virus and provoke symptoms of HZ, which is characterized by vesicles and blisters localized unilaterally and accompanied by pain. The greatest diagnostic problems occur in Zoster sine herpete and painless HZ. A significant complication of acute HZ infection is chronic postherpetic neuralgia (PHN, which manifests as dull and burning pain persisting for more than 3 months after the beginning of the rash. Senility, female gender, presence of prodromal pain, more severe skin lesions, dysaesthesia, and more intense acute PHN predispose to chronic PHN. Early diagnosis and treatment of HZ infection with antiviral medications prevent PHN. Use of local anesthetics is a very good choice in acute PHN treatment. Tricyclic antidepressants (amitriptyline, nortriptyline are conventional drugs which alleviate subacute PHN. Immunomodulatory drugs such as gabapentin help prevent or reduce the severity of PHN. The other therapeutic options are RFA (radiofrequency ablation, TENS (transcutaneous electrical nerve stimulation, physical methods such as magnetotherapy and laser therapy. The attenuated vaccine, used in patients over 60 years old, is expected to prevent the occurrence of PHN.

Treatment of patients with acute colonic diverticulitis complicated by abscess formation

DEFF Research Database (Denmark)

Gregersen, Rasmus; Mortensen, Laura Quitzau; Burcharth, Jakob

2016-01-01

by indication. Diverticular abscesses with diameters less than 3 cm might be sufficiently treated with antibiotics, while the best treatment for larger abscesses remains uncertain. Acute surgery should be reserved for critically ill patients failing non-operative treatment. Further research is needed...... to determine the best treatment for different sizes and types of diverticular abscesses, preferably randomized controlled trials....

Adjuvant intravenous methotrexate or definitive radiotherapy alone for advanced squamous cancers of the oral cavity, oropharynx, supraglottic larynx or hypopharynx

International Nuclear Information System (INIS)

Fazekas, J.T.; Sommer, C.; Kramer, S.

1980-01-01

Three hundred twenty-six patients with advanced head and neck cancers were randomized to receive definitive radiotherapy alone while 312 similar patients first received intravenous Methotrexate. No significant bias was demonstrated between the two patient populations. The number of annual deaths among the two randomized categories was essentially equal during the first 5 years. Nearly one-half occurred in the first year (146 for radiation alone and 143 in the chemotherapy plus irradiation groups). Median metastasis-free survival was between 12 to 13 months in both categories. The unadjusted 5 year survivals were in the 11 to 22% range for oral cavity, oropharynx, and supraglottic larynx and 3 to 9% for hypopharynx primaries. Although several variables did exert an impact upon survival, primary (T) and lymph node (N) stage seem to be of paramount importance and Methotrexate of minor consideration. Median and 5-year survivals within the various anatomic regions were consistently better when Methotrexate was given. However, these improvements were minimal and depended upon whether comparisons were performed on adjusted or unadjusted survival figures. In view of the modest benefits attained by using this Methotrexate regimen the authors suggest that other adjuvant programs be investigated and that this schedule not be adopted for routine clinical usage

Successful Management of Cervical Ectopic Pregnancy with Bilateral Uterine Artery Embolization and Methotrexate

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Keitaroh Takeda

2018-01-01

Full Text Available Cervical ectopic pregnancy (CEP is a rare form of ectopic pregnancy. Cases diagnosed early in pregnancy can be managed medically, but more advanced pregnancies often require hysterectomy. Uterine artery embolization (UAE is a novel approach to CEP for those who wish to preserve fertility. Here we present the case of a 44-year-old female with a 2-week history of vaginal bleeding and abdominal pain who was diagnosed with CEP and successfully treated with bilateral UAE (BUAE in combination with methotrexate. A 44-year-old female presented to the emergency department with a 2-week history of vaginal bleeding. Serum beta-hCG was 71,964 mIU/ml. The transvaginal ultrasound confirmed CEP. The patient was referred to obstetrics and interventional radiology and ultimately treated with BUAE and methotrexate. Symptoms resolved quickly and she was discharged after 3 days.

Comparative efficacy and safety of local and systemic methotrexate injection in cesarean scar pregnancy

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Peng P

2015-01-01

Full Text Available Ping Peng,1 Ting Gui,1 Xinyan Liu,1 Weilin Chen,1 Zhenzhen Liu2 1Department of Obstetrics and Gynecology, 2Department of Ultrasonography, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China Objective: To investigate the efficacy of methotrexate (MTX injection in treatment of cesarean scar pregnancy (CSP. Method: A randomized controlled study was performed in 104 CSP patients receiving either local or systemic MTX injection at the Peking Union Medical College Hospital from the year 2008 to 2013. Results: Complete cure was defined as regression of ultrasonographic findings and normalization of serum β-hCG within 60 days. It was regarded as delayed cure if additional dilation and curettage (D&C was needed. The overall cure rate (complete cure plus delayed cure was 69.2% versus 67.3% for local injection versus systemic administration (P>0.05. The median time for serum β-hCG remission and uterine mass disappearance after systemic administration (42 [21–69] days and 40 [20–67] days were significantly lower than those receiving local injection (56 [24–92] days and 53 [23–88] days, with P=0.029 and 0.046, respectively. The mean pretreatment serum β-hCG (human chorionic gonadotropin level and lesion size in cured group (21,941±18,351 mIU/mL and 2.9±1.3 cm, respectively were significantly lower than those in the failed group (37,047±30,864 mIU/mL and 3.6±1.3 with P=0.038 and 0.044, respectively. Conclusion: MTX injection is effective in CSP treatment. Systemic administration shows similar overall cure rate compared to local injection, but requires shorter time for serum β-hCG remission and uterine mass disappearance. Keywords: cesarean scar pregnancy, methotrexate injection, local, systemic

A randomized trial of treatment for acute anterior cruciate ligament tears

DEFF Research Database (Denmark)

Frobell, Richard B; Roos, Ewa M; Roos, Harald P

2010-01-01

no significant differences between the two treatment groups with respect to secondary outcomes. Adverse events were common in both groups. The results were similar when the data were analyzed according to the treatment actually received. CONCLUSIONS: In young, active adults with acute ACL tears, a strategy...

MODERN MANAGEMENT OF ACUTE RESPIRATORY INFECTIONS IN CHILDREN. RECOURSES OF SYSTEM ANTI INFLAMMATORY TREATMENT

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O.V. Zaitseva

2008-01-01

Full Text Available A problem of etiology and pathogenesis of acute respiratory infections in children are observed in this article. Modern approach to management of its treatment in pediatric patients, including often ailing children, is described. Authors give characteristics to main directions of treatment of obstructive syndrome. An experience of anti-inflammatory therapy with fenspiride (eurespal in children of different age is summa ized in this article.Key words: often ailing children, acute respiratory infections, bronchoobstructive syndrome, anti-inflammatory treatment, fenspiride.

The interventional treatment of acute renal infarction:clinical experience in six cases

International Nuclear Information System (INIS)

Wang Kai; Jiang Guomin; Zhao Jinwei; Li Shaoqin; Tian Feng; Huang Wenhua; Zhang Xianshun; Liu Yizhi

2010-01-01

Objective: To discuss the clinical characteristics of acute renal infarction and to evaluate the endovascular interventional therapy in treating acute renal infarction. Methods: Since 2006, six patients with acute renal infarction were encountered in our hospital. Renal arterial suction and thrombolytic therapy were immediately carried out as soon as the diagnosis was confirmed. The clinical data were retrospectively analyzed. Results: Based on clinical manifestations, enhanced CT scan and angiography, the diagnosis of acute renal infarction was definitely confirmed in all 6 patients. After renal arterial suction and thrombolytic therapy the clinical symptoms were markedly relieved and the blood flow in infracted area completely or partially returned to normal. Conclusion: The clinical presentation of acute renal infarction is not characteristic. For the diagnosis of acute renal infarction contrast-enhanced CT scanning and renal angiography are the exams of first choice. Renal artery suction and thrombolytic therapy is a safe and effective treatment for acute renal infarction. (authors)

Acute recurrent pancreatitis: Etiopathogenesis, diagnosis and treatment

Science.gov (United States)

Testoni, Pier Alberto

2014-01-01

Acute recurrent pancreatitis (ARP) refers to a clinical entity characterized by episodes of acute pancreatitis which occurs on more than one occasion. Recurrence of pancreatitis generally occurs in a setting of normal morpho-functional gland, however, an established chronic disease may be found either on the occasion of the first episode of pancreatitis or during the follow-up. The aetiology of ARP can be identified in the majority of patients. Most common causes include common bile duct stones or sludge and bile crystals; sphincter of oddi dysfunction; anatomical ductal variants interfering with pancreatic juice outflow; obstruction of the main pancreatic duct or pancreatico-biliary junction; genetic mutations; alcohol consumption. However, despite diagnostic technologies, the aetiology of ARP still remains unknown in up to 30% of cases: in these cases the term “idiopathic” is used. Because occult bile stone disease and sphincter of oddi dysfunction account for the majority of cases, cholecystectomy, and eventually the endoscopic biliary and/or pancreatic sphincterotomy are curative in most of cases. Endoscopic biliary sphincterotomy appeared to be a curative procedure per se in about 80% of patients. Ursodeoxycholic acid oral treatment alone has also been reported effective for treatment of biliary sludge. In uncertain cases toxin botulin injection may help in identifying some sphincter of oddi dysfunction, but this treatment is not widely used. In the last twenty years, pancreatic endotherapy has been proven effective in cases of recurrent pancreatitis depending on pancreatic ductal obstruction, independently from the cause of obstruction, and has been widely used instead of more aggressive approaches. PMID:25493002

PIDOTIMOD IN TREATMENT OF ACUTE RESPIRATORY INFECTION IN FREQUENTLY AILING CHILDREN

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F.S. Kharlamova

2009-01-01

Full Text Available This trial studied effectiveness and safety of pidotimoid (Imunorix in complex treatment of children with acute respiratory infection (ARI. Treatment with pidotimoid during 2 weeks (n = 30 resulted in lesser duration of fever and intoxication symptoms, and symptoms of laryngo-tracheitis, compared to control group (n = 30. Besides, children from pidotimoid group showed more rapid transformation of dry cough to hydrated cough, and decrease of its intensity. This beneficial change was accompanied by improvement of microbiocenosis. Effectiveness of pidotimoid was estimated by 73% of doctors as «good» (67% in control group. There was no any complication, related to treatment with this medication. The rate of repeated cases of ARI was three times lower then in control group in 6 months. All patients with ARI had no recurrent laryngeal stenosis.Key words: frequently ailing children, acute respiratory infection, treatment, prophylaxis, pidotimoid.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2009;8(2:27-33

Influence of socioeconomic status on childhood acute lymphoblastic leukemia treatment in Indonesia.

Science.gov (United States)

Mostert, Saskia; Sitaresmi, Mei N; Gundy, Chad M; Sutaryo; Veerman, Anjo J P

2006-12-01

A major reason for poor survival of childhood acute lymphoblastic leukemia in developing countries is treatment refusal or abandonment. This can be associated with parental socioeconomic status and attitudes of health care providers. Our study examined the influence of 2 socioeconomic status determinants, parental income and education, on treatment in an Indonesian academic hospital. Medical charts of 164 patients who received a diagnosis of acute lymphoblastic leukemia between 1997 and 2002 were abstracted retrospectively. Data on treatment results and parental financial and educational background were collected. Open interviews were conducted with parents and health care providers. Of all patients, 35% refused or abandoned treatment, 23% experienced treatment-related death, 22% had progressive or relapsed leukemia, and 20% had an overall event-free survival. Treatment results differed significantly between patients with different socioeconomic status; 47% of poor and 2% of prosperous patients refused or abandoned treatment. Although poor and prosperous patients used the same protocol, the provided treatment differed. Poor patients received less individualized attention from oncologists and less structured parental education. Strong social hierarchical structures hindered communication with doctors, resulting in a lack of parental understanding of the necessity to continue treatment. Most poor patients could not afford treatment. Access to donated chemotherapy also was inadequate. Treatment refusal or abandonment frequently resulted. There was no follow-up system to detect and contact dropouts. Health care providers were not fully aware that their own attitude and communication skills were important for ensuring compliance of patients and parents. Children's survival of acute lymphoblastic leukemia in developing countries could improve if problems that are associated with parental financial and educational background and medical teams' attitudes to treatment and

Clinical and radiographic outcome of a treat-to-target strategy using methotrexate and intra-articular glucocorticoids with or without adalimumab induction

DEFF Research Database (Denmark)

Hørslev-Petersen, K; Hetland, M L; Ørnbjerg, L M

2015-01-01

OBJECTIVES: To study clinical and radiographic outcomes after withdrawing 1 year's adalimumab induction therapy for early rheumatoid arthritis (eRA) added to a methotrexate and intra-articular triamcinolone hexacetonide treat-to-target strategy (NCT00660647). METHODS: Disease-modifying antirheuma......OBJECTIVES: To study clinical and radiographic outcomes after withdrawing 1 year's adalimumab induction therapy for early rheumatoid arthritis (eRA) added to a methotrexate and intra-articular triamcinolone hexacetonide treat-to-target strategy (NCT00660647). METHODS: Disease.......12). Erosive progression (Δerosion score (ES)/year) was year 1:0.57/0.06 (p=0.02); year 2:0.38/0.05 (p=0.005). Proportion of patients without erosive progression (ΔES≤0) was year 1: 59%/76% (p=0.03); year 2:64%/79% (p=0.04). CONCLUSIONS: An aggressive triamcinolone and synthetic DMARD treat-to-target strategy...... was (re)initiated in 12/12 patients and cumulative triamcinolone dose was 160/120 mg (p=0.15). The treatment target (disease activity score, 4 variables, C-reactive protein (DAS28CRP) ≤3.2 or DAS28>3.2 without swollen joints) was achieved at all visits in ≥85% of patients in year 2; remission rates were...

Current Canadian And American Experiences In The Treatment Of Acute Ischemic Stroke

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Parviz Dolati

2017-02-01

Full Text Available Stroke remains one of the main public health issues worldwide. It is the third leading cause of death in the United States, with more than 200,000 people dying from strokes each year. Approximately 80% of all acute ischemic strokes are due to intracranial artery occlusion, most commonly thromboembolic clot occlusion. Revascularization of occluded territories is the cornerstone of acute ischemic stroke and Thrombolysis for ischemic stroke has been systematically studied in large randomized trials only since the 1990s. To date, thrombolytic therapy for ischemic stroke has been investigated in 21 randomized controlled clinical trials enrolling more than 7,000 patients. The advent of modern imaging and endovascular tools and technology has revolutionized treatment of stroke. In this talk, I will review current clinical trials published in The NEJM (ESCAPE, MR Clean, EXTENDED IA, …. regarding superiority of the endovascular treatments, especially, the stent retrievers, over Iv tPA. I will also go over all endovascular techniques used in the endovascular treatment of acute stroke using my Canadian and American experiences.

[The use of Timalin in the treatment of the acute lung abscess].

Science.gov (United States)

Tsybikov, M N; Likhanov, I D; Borshchevskiĭ, V S; Kuznik, B I; Tsepelev, V L; Maslo, E Iu; Tsybikov, N N

2012-01-01

The study was aimed to research levels of main acute inflammation phase peptides, coagulative and fibrinolitic plasma activity on the background of traditional treatment and with addition of Timalin in patients with acute lung abscess. The study demonstrated that induction of bioregulative therapy leads to faster normalization of main indicators of SIRS and plasma fibrinolitic activity and eliminates hypercoagulation.

The variation of acute treatment costs of trauma in high-income countries.

Science.gov (United States)

Willenberg, Lynsey; Curtis, Kate; Taylor, Colman; Jan, Stephen; Glass, Parisa; Myburgh, John

2012-08-21

In order to assist health service planning, understanding factors that influence higher trauma treatment costs is essential. The majority of trauma costing research reports the cost of trauma from the perspective of the receiving hospital. There has been no comprehensive synthesis and little assessment of the drivers of cost variation, such as country, trauma, subgroups and methods. The aim of this review is to provide a synthesis of research reporting the trauma treatment costs and factors associated with higher treatment costs in high income countries. A systematic search for articles relating to the cost of acute trauma care was performed and included studies reporting injury severity scores (ISS), per patient cost/charge estimates; and costing methods. Cost and charge values were indexed to 2011 cost equivalents and converted to US dollars using purchasing power parities. A total of twenty-seven studies were reviewed. Eighty-one percent of these studies were conducted in high income countries including USA, Australia, Europe and UK. Studies either reported a cost (74.1%) or charge estimate (25.9%) for the acute treatment of trauma. Across studies, the median per patient cost of acute trauma treatment was $22,448 (IQR: $11,819-$33,701). However, there was variability in costing methods used with 18% of studies providing comprehensive cost methods. Sixty-three percent of studies reported cost or charge items incorporated in their cost analysis and 52% reported items excluded in their analysis. In all publications reviewed, predictors of cost included Injury Severity Score (ISS), surgical intervention, hospital and intensive care, length of stay, polytrauma and age. The acute treatment cost of trauma is higher than other disease groups. Research has been largely conducted in high income countries and variability exists in reporting costing methods as well as the actual costs. Patient populations studied and the cost methods employed are the primary drivers for the

The variation of acute treatment costs of trauma in high-income countries

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Willenberg Lynsey

2012-08-01

Full Text Available Abstract Background In order to assist health service planning, understanding factors that influence higher trauma treatment costs is essential. The majority of trauma costing research reports the cost of trauma from the perspective of the receiving hospital. There has been no comprehensive synthesis and little assessment of the drivers of cost variation, such as country, trauma, subgroups and methods. The aim of this review is to provide a synthesis of research reporting the trauma treatment costs and factors associated with higher treatment costs in high income countries. Methods A systematic search for articles relating to the cost of acute trauma care was performed and included studies reporting injury severity scores (ISS, per patient cost/charge estimates; and costing methods. Cost and charge values were indexed to 2011 cost equivalents and converted to US dollars using purchasing power parities. Results A total of twenty-seven studies were reviewed. Eighty-one percent of these studies were conducted in high income countries including USA, Australia, Europe and UK. Studies either reported a cost (74.1% or charge estimate (25.9% for the acute treatment of trauma. Across studies, the median per patient cost of acute trauma treatment was $22,448 (IQR: $11,819-$33,701. However, there was variability in costing methods used with 18% of studies providing comprehensive cost methods. Sixty-three percent of studies reported cost or charge items incorporated in their cost analysis and 52% reported items excluded in their analysis. In all publications reviewed, predictors of cost included Injury Severity Score (ISS, surgical intervention, hospital and intensive care, length of stay, polytrauma and age. Conclusion The acute treatment cost of trauma is higher than other disease groups. Research has been largely conducted in high income countries and variability exists in reporting costing methods as well as the actual costs. Patient populations studied

The role of nanoparticles in the albumin-cytarabine and albumin-methotrexate interactions