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Uterine-conserving approach in ruptured intramyometrial ectopic pregnancy

Esther LSY, Chew KT, Rahman RA, Zainuddin AA, Hing EY, Kampan N

Horm Mol Biol Clin Investig, 2020 Mar 13;41(2).
PMID: 32167930 DOI: 10.1515/hmbci-2020-0001

Intramyometrial ectopic pregnancy (IMEP) is a rare form of ectopic pregnancy. It is defined as a conceptus implanted within the myometrium and is completely surrounded by myometrium with clear separation from both the uterine cavity and tubes. IMEP possesses not only diagnostic but also therapeutic challenge. The majority of reported cases were managed by hysterectomy. Early management of unruptured IMEP using methotrexate may help to preserve fertility. We, for the first time, report a case of ruptured IMEP managed successfully using suction and curettage followed by Bakri balloon tamponade and avoiding hysterectomy. Post-procedure, the patient received two doses of intramuscular methotrexate 50 mg/m2 due to plateauing serial beta human chorionic gonadotropin (β-hCG) levels and subsequently achieved undetectable level 10 weeks post-methotrexate. She also had complete resolution of the ectopic intramyometrial mass.

Matched MeSH terms: Methotrexate/therapeutic use
Fulltext Unruptured left cornual pregnancy with a high serum β-hCG: a case report

Nirmala, C.K., Lim, P.S., Norzilawati, M.N., Zainul, R.A.Z., Mohd. Hashim, O.

Journal of Surgical Academia, 2011;1(1):49-51.
MyJurnal

Ectopic pregnancy in the interstitial part of the fallopian tube (cornual pregnancy) is a rare condition but can be fatal. Traditionally, the treatment had been cornual resection or hysterectomy. More conservative approaches had been advocated recently. There is no consensus on the dose or number of methotrexate injections that should be used in the treatment of interstitial pregnancies. Single dose intramuscular methotrexate is one of the treatment options. However, the failure rate is higher if the serum beta-hCG (beta-human chorionic gonadotrophin) level is more than 5000 IU/L. We report a case of cornual ectopic pregnancy with high initial serum beta-hCG level being successfully treated with multiple doses of systemic methotrexate. MRI was used to assess clinical resolution of cornual ectopic pregnancy.

Matched MeSH terms: Methotrexate
Fulltext Tuberculosis and biologics - a glimpse of Sabah rheumatology patients

Le Low, Darman Shah N. S., Mohd Noh M., Y. Y. Chong

Malaysian Journal of Medicine and Health Sciences, 2019;15(106):66-66.
MyJurnal

Introduction: Biologic patients are at increased risk of tuberculosis (TB) infection, especially in TB prevalent areas like Sabah. We present three cases of rheumatology patients who developed tuberculosis infection while on bi-ologics. Case description: Case1: 47 year old lady with active rheumatoid arthritis despite being on four disease modifying antirheumatic drugs (DMARDS) was given subcutaneous Etanercept after prescreening with mantoux test and interferon gamma release assay (IGRA). Due to poor response, she was switched to Tofacitinib with a repeat pre-screening done except IGRA. Three months after biologics, she developed pulmonary tuberculosis and Tofacitinib was stopped. Case2: 50 year old male with seropositive rheumatoid arthritis and seroconverted hepatitis B. He was worked up for biologic treatment after failing multiple DMARDS; mantoux was 10mm, IGRA not done. He was start-ed on subcutaneous Etanercept for disabling arthritis while being treated for latent TB but developed TB Lymphadeni-tis on his third month of biologic therapy which was withheld thereafter. Case3:48 year old teacher with seropositive rheumatoid arthritis and old pulmonary TB, had intolerance to methotrexate, was initiated on three DMARDS but symptoms remained uncontrolled. Prescreening with IGRA was negative and Adalimumab commenced. Following two years of biologic, she developed reactivation of TB. Rituximab was commenced a year after for persistent active arthritis but withheld due to dermatitis. Conclusion: All patients had mantoux test done routinely but not IGRA due to its cost and limited availability. A follow up study to analyze the effectiveness of IGRA versus Mantoux in detecting latent TB in such patients would be beneficial.

Matched MeSH terms: Methotrexate
Treatment of skin diseases: recent trends

Adam BA

Med J Malaysia, 1973 Mar;27(3):192-4.
PMID: 4268922
Matched MeSH terms: Methotrexate/therapeutic use
Treatment of childhood acute lymphoblastic leukemia in Malaysia, 1976-1982

Lin HP, Sinnah D, Menaka N, Cherian R, Singh P

Med. Pediatr. Oncol., 1983;11(5):327-32.
PMID: 6579342

One hundred four children with acute lymphoblastic leukaemia were diagnosed at the University Hospital, Kuala Lumpur, Malaysia, between 1976 and 1982; 87 were evaluable with respect to treatment. They were divided into good prognosis (GP) and bad prognosis (BP) groups based on their initial total white cell count, their treatment differing only during the maintenance phase. Remission was achieved in 82 patients (94%) of whom ten (12%) subsequently died in remission from infection. Twenty-eight (34%) relapsed while on treatment and three while off therapy. Eleven patients ceased treatment after 3 yr of continuous complete remission (CCR). Three of these later relapsed, two within the first year. Survival in CCR was significantly better in the GP group up to 30 months, after which the difference diminished. There was no difference in survival between boys and girls. The overall disease-free survival at 3 yr and 5 yr was 40% and 25%, respectively, with a median follow-up period of 20 months (range 4-69 months). The reasons for the relatively low survival rates as compared with those in developed countries are discussed.

Matched MeSH terms: Methotrexate/administration & dosage
Fulltext Transverse myelopathy following intrathecal administration of chemotherapy

Teh HS, Fadilah SA, Leong CF

Singapore Med J, 2007 Feb;48(2):e46-9.
PMID: 17304378

Transverse myelopathy is one of the rare complications following administration of intrathecal chemotherapy. We report two cases of transverse myelopathy following administration of intrathecal methotrexate and cytarabine arabinoside. One patient was a 17-year-old Malay man who had lymphoblastic lymphoma in the leukaemic phase, while the other patient was a 40-year-old Malay man with relapsed Hodgkin's lymphoma. Both cases demonstrated variability in onset of symptoms, clinical progression and final outcome from the complication.

Matched MeSH terms: Methotrexate/adverse effects*
Fulltext Transcriptome analysis of Streptococcus pneumoniae treated with the designed antimicrobial peptides, DM3

Le CF, Gudimella R, Razali R, Manikam R, Sekaran SD

Sci Rep, 2016 05 26;6:26828.
PMID: 27225022 DOI: 10.1038/srep26828

In our previous studies, we generated a short 13 amino acid antimicrobial peptide (AMP), DM3, showing potent antipneumococcal activity in vitro and in vivo. Here we analyse the underlying mechanisms of action using Next-Generation transcriptome sequencing of penicillin (PEN)-resistant and PEN-susceptible pneumococci treated with DM3, PEN, and combination of DM3 and PEN (DM3PEN). DM3 induced differential expression in cell wall and cell membrane structural and transmembrane processes. Notably, DM3 altered the expression of competence-induction pathways by upregulating CelA, CelB, and CglA while downregulating Ccs16, ComF, and Ccs4 proteins. Capsular polysaccharide subunits were downregulated in DM3-treated cells, however, it was upregulated in PEN- and DM3PEN-treated groups. Additionally, DM3 altered the amino acids biosynthesis pathways, particularly targeting ribosomal rRNA subunits. Downregulation of cationic AMPs resistance pathway suggests that DM3 treatment could autoenhance pneumococci susceptibility to DM3. Gene enrichment analysis showed that unlike PEN and DM3PEN, DM3 treatment exerted no effect on DNA-binding RNA polymerase activity but observed downregulation of RpoD and RNA polymerase sigma factor. In contrast to DM3, DM3PEN altered the regulation of multiple purine/pyrimidine biosynthesis and metabolic pathways. Future studies based on in vitro experiments are proposed to investigate the key pathways leading to pneumococcal cell death caused by DM3.

Matched MeSH terms: Methotrexate
Fulltext The identification of novel Mycobacterium tuberculosis DHFR inhibitors and the investigation of their binding preferences by using molecular modelling

Hong W, Wang Y, Chang Z, Yang Y, Pu J, Sun T, et al.

Sci Rep, 2015;5:15328.
PMID: 26471125 DOI: 10.1038/srep15328

It is an urgent need to develop new drugs for Mycobacterium tuberculosis (Mtb), and the enzyme, dihydrofolate reductase (DHFR) is a recognised drug target. The crystal structures of methotrexate binding to mt- and h-DHFR separately indicate that the glycerol (GOL) binding site is likely to be critical for the function of mt-DHFR selective inhibitors. We have used in silico methods to screen NCI small molecule database and a group of related compounds were obtained that inhibit mt-DHFR activity and showed bactericidal effects against a test Mtb strain. The binding poses were then analysed and the influence of GOL binding site was studied by using molecular modelling. By comparing the chemical structures, 4 compounds that might be able to occupy the GOL binding site were identified. However, these compounds contain large hydrophobic side chains. As the GOL binding site is more hydrophilic, molecular modelling indicated that these compounds were failed to occupy the GOL site. The most potent inhibitor (compound 6) demonstrated limited selectivity for mt-DHFR, but did contain a novel central core (7H-pyrrolo[3,2-f]quinazoline-1,3-diamine), which may significantly expand the chemical space of novel mt-DHFR inhibitors. Collectively, these observations will inform future medicinal chemistry efforts to improve the selectivity of compounds against mt-DHFR.

Matched MeSH terms: Methotrexate
Fulltext The atypical presentation of rheumatoid arthritis in an elderly woman: a case report

Devaraj NK

Ethiop J Health Sci, 2019 Jan;29(1):957-958.
PMID: 30700964 DOI: 10.4314/ejhs.v29i1.18

The diagnosis of rheumatologic problem can be difficult, especially if not all the diagnostic criteria or typical clinical features are seen. This includes conditions such as rheumatoid arthritis which needs early diagnosis to start disease modifying drugs (DMARDs) which can improve the prognosis and prevent further joint erosion and organ damage. This case report focused on a similar scenario in an elderly woman initially thought to have osteoarthritis but was diagnosed later with rheumatoid arthritis which brought much relief to her current predicament.

Matched MeSH terms: Methotrexate/therapeutic use
Term interstitial pregnancy with uterine conservation

Ng PH, NorAzlin MI, Nasri NI

Int J Gynaecol Obstet, 2007 Dec;99(3):251.
PMID: 17888439
Matched MeSH terms: Methotrexate/administration & dosage*
Successful treatment of paediatric generalized pustular psoriasis with secukinumab: a case series

Albela H, Begum S, Leong KF

J Dermatolog Treat, 2021 Mar 11.
PMID: 33706651 DOI: 10.1080/09546634.2021.1899111

Generalized Pustular Psoriasis (GPP) is a rare, severe, life-threatening form of psoriasis and accounts for up to 13.1% of all childhood psoriasis. Common first-line systemic treatment for pediatric patients with GPP include oral acitretin, cyclosporin and methotrexate which have varying efficacy and side effects but multiple interventions are often needed to induce remission and maintain long term control. Recently, the anti IL 17 A monoclonal antibody secukinumab have been shown to be effective in adult patients with GPP; however, there is lack of evidence of its usage in the pediatric population. We describe a case series of 4 pediatric patients with GPP who were treated with off-label use of secukinumab. All four patients had marked clearance and reduction in Generalized Pustular Psoriasis Area & Severity Score (GPPASI) within first 48 h of first injection with subsequent almost complete to complete clearance of skin lesions by 1 month follow up. In conclusion, secukinumab was found to be successful in inducing remission, with rapid clearance and maintaining remission, with or without combination with other systemic agents for pediatric GPP.

Matched MeSH terms: Methotrexate
Stopping anti-tumour necrosis factor therapy in patients with perianal Crohn's disease

Mak JWY, Tang W, Yip TCF, Ran ZH, Wei SC, Ahuja V, et al.

Aliment Pharmacol Ther, 2019 12;50(11-12):1195-1203.
PMID: 31638274 DOI: 10.1111/apt.15547

BACKGROUND: Little is known of the outcome of patients with perianal Crohn's disease after stopping anti-tumour necrosis factor (TNF) therapy.
AIM: To evaluate the rate of relapse in perianal Crohn's disease (CD) after stopping anti-TNF therapy.
METHODS: Consecutive perianal CD patients treated with anti-TNF therapy with subsequent discontinuation were retrieved from prospective inflammatory bowel disease database of institutes in Hong Kong, Shanghai, Taiwan, Malaysia, Thailand and Singapore from 1997 to June 2019. Cumulative probability of perianal CD relapse was estimated using Kaplan-Meier method.
RESULTS: After a median follow-up of 89 months (interquartile range [IQR]: 65-173 months), 44 of the 78 perianal CD patients (56.4%) relapsed after stopping anti-TNF, defined as increased fistula drainage or recurrence of previously healed fistula, after stopping anti-TNF therapy. Cumulative probabilities of perianal CD relapse were 50.8%, 72.6% and 78.0% at 12, 36 and 60 months, respectively. Younger age at diagnosis of CD [adjusted hazard ratio (HR): 1.04; 95% CI 1.01-1.09; P = .04] was associated with a higher chance of perianal CD relapse. Among those with perianal CD relapse (n = 44), retreatment with anti-TNF induced remission in 24 of 29 patients (82.8%). Twelve (27.3%) patients required defunctioning surgery and one (2.3%) required proctectomy. Maintenance with thiopurine was not associated with a reduced likelihood of relapse [HR = 1.10; 95% CI: 0.58-2.12; P = .77]. Among the 17 patients who achieved radiological remission of perianal CD, five (35.3%) developed relapse after stopping anti-TNF therapy after a median of 6 months.
CONCLUSIONS: More than half of the perianal CD patients developed relapse after stopping anti-TNF therapy. Most regained response after resuming anti-TNF. However, more than one-fourth of the perianal CD patients with relapse required defunctioning surgery. Radiological assessment before stopping anti-TNF is crucial in perianal CD.

Matched MeSH terms: Methotrexate/therapeutic use
Fulltext Sequential Proximal Tibial Stress Fractures associated with Prolonged usage of Methotrexate and Corticosteroids: A Case Report

Tan T, Ho W

Malays Orthop J, 2015 Nov;9(3):65-67.
PMID: 28611915 DOI: 10.5704/MOJ.1511.010

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.

Matched MeSH terms: Methotrexate
Fulltext Role of nitric oxide-scavenging activity of Karanjin and Pongapin in the treatment of Psoriasis

Ghosh A, Tiwari GJ

3 Biotech, 2018 Aug;8(8):338.
PMID: 30073123 DOI: 10.1007/s13205-018-1337-5

In the present study, Karanjin and Pongapin, two important furanoflavone, constituents of Pongamia pinnata were studied in the management of Psoriasis. Presently, we have experimentally studied the free radical quenching property of Karanjin and Pongapin. A modified method was used to estimate the scavenging effect of the Karanjin (the highest activity of 95.60%) and Pongapin (68.05%) compared to the ascorbic acid as standard (11.60%) against nitric oxide. Furthermore, Molecular docking studies were performed using CLC drug discovery workbench software version 3.0 of the studied flavones (Karanjin and Pongapin) with the receptors responsible for psoriasis (viz. IL-17A, IL-17F, IL-23, RORγt, and TLR-7). Docking scores of Karanjin and Pongapin with different studied receptors were found to be comparable to that of Methotrexate, a known drug for treating Psoriasis. Docking results suggest that Karanjin and Pongapin might also help in controlling the disease. Overall, our results indicate that flavones (Karanjin and Pongapin) could be a natural and better alternative in curing psoriasis without any side effects.

Matched MeSH terms: Methotrexate
Fulltext Rheumatoid arthritis serotype and synthetic disease-modifying anti-rheumatic drugs in patients with periodontitis: A case-control study

Nik-Azis NM, Mohd N, Mohd Fadzilah F, Mohamed Haflah NH, Mohamed Said MS, Baharin B

PLoS One, 2021;16(6):e0252859.
PMID: 34153036 DOI: 10.1371/journal.pone.0252859

Patients with rheumatoid arthritis (RA) experience a higher prevalence of periodontitis. This study aimed to examine the variation of periodontitis experienced with different serotypes suffered by RA patients and to examine the relationship between the different medications taken for RA that may influence this relationship. Two hundred and sixty RA and control participants underwent standardized periodontal examinations. Medical, serological and radiological (Sharp/van der Heijde) records were assessed. Functional status was assessed using the administered Health Assessment Questionnaire. Moreover, disease parameters, including disease activity (DAS28-ESR) and anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF) seropositivity were evaluated. Periodontitis was higher in RA (71.54%) compared with controls (54.62%). The stage of periodontitis experienced by ACPA-positive participants were higher than APCA-negative participants. The probing pocket depth and recession experienced by RF-positive participants were higher than those who were RF-negative. RA participants on methotrexate had lower clinical attachment loss and lower periodontal probing depth compared with participants on a combination methotrexate and other disease-modifying antirheumatic drugs. Participants taking corticosteroids had lower gingival index scores. The association between seropositivity and the type of medications taken with periodontal health parameters in this group of patients suggests that both seropositivity and medications taken are important modifiers in the relationship between periodontitis and RA.

Matched MeSH terms: Methotrexate/pharmacology
Relapsed lymphoma mimicking venous ulcer: A case report

Kamal WSA, Affandi AM, Bhullar A, Kamal WSZ

Med J Malaysia, 2018 08;73(4):253-254.
PMID: 30121690 MyJurnal

Lymphoma presenting with ulceration is not typical. We report a case of relapsed DLBCL in a 73-year-old man presenting with a chronic non-healing leg ulcer. He has underlying varicose veins with recurrent venous ulcers. This patient was diagnosed to have DLBCL six years earlier when he presented with recurrent epistaxis originating from a left nasal cavity nodule. Complete resolution was achieved after eight cycles of R-CHOP and intrathecal methotrexate. For this current problem, this patient was treated with rituximab combined with chemotherapy which resulted in healing of the ulcer.

Matched MeSH terms: Methotrexate/administration & dosage; Methotrexate/therapeutic use
Recent advances and prospects in gemcitabine drug delivery systems

Paroha S, Verma J, Dubey RD, Dewangan RP, Molugulu N, Bapat RA, et al.

Int J Pharm, 2021 Jan 05;592:120043.
PMID: 33152476 DOI: 10.1016/j.ijpharm.2020.120043

Cancer is a community health hazard which progress at a fatal rate in various countries across the globe. An agent used for chemotherapy should exhibit ideal properties to be an effective anticancer medicine. The chemotherapeutic medicines used for treatment of various cancers are, gemcitabine, paclitaxel, etoposide, methotrexate, cisplatin, doxorubicin and 5-fluorouracil. However, many of these agents present nonspecific systemic toxicity that prevents their treatment efficiency. Of all, gemcitabine has shown to be an active agent against colon, pancreatic, colon, ovarian, breast, head and neck and lung cancers in amalgamation with various anticancer agents. Gemcitabine is considered a gold-standard and the first FDA approved agent used as a monotherapy in management of advanced pancreatic cancers. However due to its poor pharmacokinetics, there is need of newer drug delivery system for efficient action. Nanotechnology has shown to be an emerging trend in field of medicine in providing novel modalities for cancer treatment. Various nanocarriers have the potential to deliver the drug at the desired site to obtain information about diagnosis and treatment of cancer. This review highlights on various nanocarriers like polymeric nanoparticles, solid lipid nanoparticles, mesoporous silica nanoparticles, magnetic nanoparticles, micelles, liposomes, dendrimers, gold nanoparticles and combination approaches for delivery of gemcitabine for cancer therapy. The co-encapsulation and concurrent delivery of Gem with other anticancer agents can enhance drug action at the cancer site with reduced side effects.

Matched MeSH terms: Methotrexate
Fulltext Real-world experiences of folic acid supplementation (5 versus 30 mg/week) with methotrexate in rheumatoid arthritis patients: a comparison study

Koh KT, Teh CL, Cheah CK, Ling GR, Yong MC, Hong HC, et al.

Reumatismo, 2016 Sep 09;68(2):90-6.
PMID: 27608797 DOI: 10.4081/reumatismo.2016.872

The objective of this study was to compare the tolerability of methotrexate in two different regimes of folic acid (FA) supplementation in rheumatoid arthritis (RA). We performed a multicenter, cross-sectional observational cohort study on 240 RA patients with 120 patients each in 5 mg of FA weekly and 30 mg of FA weekly supplementation. There were no significant differences for side effects (14.2 versus 22.5%, P=0.523) and discontinuation of methotrexate (3.6 versus 13.3%, P=0.085). RA patients given 5 mg of FA weekly supplementation had a lower disease activity score 28 compared to 30 mg of FA weekly supplementation [3.44 (1.10) versus 3.85 (1.40), P=0.014]. FA supplementation of 5 mg per week and 30 mg per week was associated with similar tolerability of methotrexate in RA patients.

Matched MeSH terms: Methotrexate/therapeutic use*
Real-world clinical experience of biological disease modifying anti-rheumatic drugs in Malaysia rheumatoid arthritis patients

Tan BE, Lim AL, Kan SL, Lim CH, Tsang EEL, Ch'ng SS, et al.

Rheumatol Int, 2017 Oct;37(10):1719-1725.
PMID: 28695274 DOI: 10.1007/s00296-017-3772-8

The effect of biologic disease modifying anti-rheumatic drugs (bDMARDs) in treating rheumatoid arthritis (RA) in real-world clinical practice remains unknown in Southeast Asia. We aimed to assess the efficacy and safety of bDMARDs among Malaysian RA patients treated in routine clinical practice. A retrospective medical chart review of RA patients from 11 government hospitals were conducted from January 2003 to January 2014. A standardized questionnaire was used to abstract patient's demographic, clinical and treatment data. Level of disease activity was measured by DAS28 collected at baseline, 3, 6 and 12 months. Three hundred and one patients were available for analysis, mean age 41 (SD, 10.8) years, mean RA duration 12.3 (SD, 6.9) years and 98% had history of two or more conventional-synthetic DMARDs. There were 467 bDMARD courses prescribed with mean bDMARDs duration use of 12.9 months (SD 14.7). Tumour necrosis factor alpha inhibitors were the most common prescribed bDMARDs (77.1%), followed by Tocilizumab (14.6%) and Rituximab (8.4%). We observed significant improvement in mean DAS28 values from baseline to 3, 6 and 12 months (p

Matched MeSH terms: Methotrexate/adverse effects; Methotrexate/therapeutic use
Raynaud's phenomenon associated with psoriatic arthritis

Che Rahim MJ, Lim JA, Wan Ghazali WS

BMJ Case Rep, 2024 Mar 05;17(3).
PMID: 38442964 DOI: 10.1136/bcr-2023-258215

We report a case of Raynaud's phenomenon in a patient with psoriatic arthritis (PsA). A middle-aged right-handed housewife presented with complaints of severely painful hand discolouration for 1 week, which usually worsened with cold exposure. She was diagnosed with PsA 6 months earlier. Her PsA was well controlled with weekly methotrexate. Physical examination showed no features of scleroderma or skin necrosis of her right hand. Both radial pulses were strong and symmetrical. Her nailfolds were visibly normal. The extractable nuclear antigen panel and other blood investigations were negative for scleroderma and other possible causes of secondary Raynaud's phenomenon. Occupational or environmental factors were also excluded. Dermatoscope examination of the nailfolds revealed some areas of dilated capillary loops, areas of vascular sparing and proximal nail fold telangiectasia. The diagnosis of secondary Raynaud's phenomenon was made, and an oral calcium channel blocker was started. The patient had significant improvement in symptoms shortly afterwards.

Matched MeSH terms: Methotrexate

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