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Combined optic neuropathy and central retinal artery occlusion in presumed ocular tuberculosis without detectable systemic infection

Ooi YL, Tai LY, Subrayan V, Tajunisah I

Ocul Immunol Inflamm, 2011 Oct;19(5):370-2.
PMID: 21834697 DOI: 10.3109/09273948.2011.594203

To report a rare case of combined optic neuropathy and central retinal artery occlusion in presumed ocular tuberculosis without systemic infection.

Matched MeSH terms: Optic Nerve Diseases/drug therapy; Tuberculosis, Ocular/drug therapy; Retinal Artery Occlusion/drug therapy
Fulltext Leveraging the advances in HIV for COVID-19

McMahon JH, Hoy JF, Kamarulzaman A, Bekker LG, Beyrer C, Lewin SR

Lancet, 2020 10 03;396(10256):943-944.
PMID: 33010825 DOI: 10.1016/S0140-6736(20)32012-2
Matched MeSH terms: Pneumonia, Viral/drug therapy; HIV Infections/drug therapy; Coronavirus Infections/drug therapy
Fulltext The effect of ketamine on emergence agitation in children: A systematic review and meta-analysis

Ng KT, Sarode D, Lai YS, Teoh WY, Wang CY

Paediatr Anaesth, 2019 12;29(12):1163-1172.
PMID: 31587414 DOI: 10.1111/pan.13752

BACKGROUND: Ketamine is believed to reduce the incidence of emergence agitation in children undergoing surgery or procedure. However, recent randomized controlled trials reported conflicting findings.
AIMS: To investigate the effect of ketamine on emergence agitation in children.
METHODS: Databases of MEDLINE, EMBASE, and CENTRAL were systematically searched from their start date until February 2019. Randomized controlled trials comparing intravenous ketamine and placebo in children were sought. The primary outcome was the incidence of emergence agitation. Secondary outcomes included postoperative pain score, duration of discharge time, and the adverse effects associated with the use of ketamine, namely postoperative nausea and vomiting, desaturation, and laryngospasm.
RESULTS: Thirteen studies (1125 patients) were included in the quantitative meta-analysis. The incidence of emergence agitation was 14.7% in the ketamine group and 33.3% in the placebo group. Children receiving ketamine had a lower incidence of emergence agitation, with an odds ratio being 0.23 (95% confidence interval: 0.11 to 0.46), certainty of evidence: low. In comparison with the placebo, ketamine group achieved a lower postoperative pain score (odds ratio: -2.42, 95% confidence interval: -4.23 to -0.62, certainty of evidence: very low) and lower pediatric anesthesia emergence delirium scale at 5 minutes after operation (odds ratio: -3.99, 95% confidence interval: -5.03 to -2.95; certainty of evidence: moderate). However, no evidence was observed in terms of incidence of postoperative nausea and vomiting, desaturation, and laryngospasm.
CONCLUSION: In this meta-analysis of 13 randomized controlled trials, high degree of heterogeneity and low certainty of evidence limit the recommendations of ketamine for the prevention of emergence agitation in children undergoing surgery or imaging procedures. However, the use of ketamine is well-tolerated without any notable adverse effects across all the included trials.
PROSPERO REGISTRATION: CRD42019131865.

Matched MeSH terms: Pain, Postoperative/drug therapy; Postoperative Nausea and Vomiting/drug therapy; Emergence Delirium/drug therapy*
Fulltext Mesenchymal chondrosarcoma of maxilla in paediatric patient

Choo CS, Wan Abdul Rahman WF, Jaafar H, Ramli RR

BMJ Case Rep, 2019 Mar 09;12(3).
PMID: 30852518 DOI: 10.1136/bcr-2018-228969

Chondrosarcoma (CS) is a malignant tumour of long and flat bone characterised by the formation of cartilage. Mesenchymal chondrosarcoma (MCS) is a rare subtype of CS that is more aggressive and may lead to erroneous diagnosis in a limited biopsy. The diagnosis is mainly based on the histopathological appearance of biphasic pattern of undifferentiated small round cells separated by islands of well-differentiated hyaline cartilage. We report a case of 13-year-old boy who initially presented with gum swelling and the biopsy result suggested a benign fibrous lesion. Following an extensive lesion shown in radiologic findings, the tumour excision was done and finally was diagnosed as an MCS of the maxilla. The patient was given postoperative chemotherapy (EURO-EWING 99 regimen), and now on regular follow-up for monitoring of local recurrence or tumour metastasis.

Matched MeSH terms: Drug Therapy/methods; Chondrosarcoma, Mesenchymal/drug therapy
Fulltext Treatment of Autosomal Dominant Hypocalcemia Type 1 With the Calcilytic NPSP795 (SHP635)

Roberts MS, Gafni RI, Brillante B, Guthrie LC, Streit J, Gash D, et al.

J. Bone Miner. Res., 2019 09;34(9):1609-1618.
PMID: 31063613 DOI: 10.1002/jbmr.3747

Autosomal dominant hypocalcemia type 1 (ADH1) is a rare form of hypoparathyroidism caused by heterozygous, gain-of-function mutations of the calcium-sensing receptor gene (CAR). Individuals are hypocalcemic with inappropriately low parathyroid hormone (PTH) secretion and relative hypercalciuria. Calcilytics are negative allosteric modulators of the extracellular calcium receptor (CaR) and therefore may have therapeutic benefits in ADH1. Five adults with ADH1 due to four distinct CAR mutations received escalating doses of the calcilytic compound NPSP795 (SHP635) on 3 consecutive days. Pharmacokinetics, pharmacodynamics, efficacy, and safety were assessed. Parallel in vitro testing with subject CaR mutations assessed the effects of NPSP795 on cytoplasmic calcium concentrations (Ca2+i ), and ERK and p38MAPK phosphorylation. These effects were correlated with clinical responses to administration of NPSP795. NPSP795 increased plasma PTH levels in a concentration-dependent manner up to 129% above baseline (p = 0.013) at the highest exposure levels. Fractional excretion of calcium (FECa) trended down but not significantly so. Blood ionized calcium levels remained stable during NPSP795 infusion despite fasting, no calcitriol supplementation, and little calcium supplementation. NPSP795 was generally safe and well-tolerated. There was significant variability in response clinically across genotypes. In vitro, all mutant CaRs were half-maximally activated (EC50 ) at lower concentrations of extracellular calcium (Ca2+o ) compared to wild-type (WT) CaR; NPSP795 exposure increased the EC50 for all CaR activity readouts. However, the in vitro responses to NPSP795 did not correlate with any clinical parameters. NPSP795 increased plasma PTH levels in subjects with ADH1 in a dose-dependent manner, and thus, serves as proof-of-concept that calcilytics could be an effective treatment for ADH1. Albeit all mutations appear to be activating at the CaR, in vitro observations were not predictive of the in vivo phenotype or the response to calcilytics, suggesting that other parameters impact the response to the drug. © 2019 American Society for Bone and Mineral Research.

Matched MeSH terms: Hypocalcemia/drug therapy*; Hypoparathyroidism/drug therapy; Hypercalciuria/drug therapy*
Fulltext The Potential Benefit of Telmisartan to Protect Overweight Patients with COPD from the Acquisition of COVID-19

Kow CS, Hasan SS

Obesity (Silver Spring), 2020 11;28(11):2035.
PMID: 32692903 DOI: 10.1002/oby.22976
Matched MeSH terms: Pneumonia, Viral/drug therapy*; Coronavirus Infections/drug therapy*; Overweight/drug therapy*
A Review on Biological Properties and Synthetic Methodologies of Diarylpentadienones

Abdullah MA, Mohd Faudzi SM, Nasir NM

Mini Rev Med Chem, 2021;21(9):1058-1070.
PMID: 33272171 DOI: 10.2174/1389557520999201203213957

Medicinal chemists have continuously shown interest in new curcuminoid derivatives, diarylpentadienones, owing to their enhanced stability feature and easy preparation using a one-pot synthesis. Thus far, methods such as Claisen-Schmidt condensation and Julia- Kocienski olefination have been utilised for the synthesis of these compounds. Diarylpentadienones possess a high potential as a chemical source for designing and developing new and effective drugs for the treatment of diseases, including inflammation, cancer, and malaria. In brief, this review article focuses on the broad pharmacological applications and the summary of the structure-activity relationship of molecules, which can be employed to further explore the structure of diarylpentadienone. The current methodological developments towards the synthesis of diarylpentadienones are also discussed.

Matched MeSH terms: Inflammation/drug therapy; Malaria/drug therapy; Neoplasms/drug therapy*
Trichosporon Asahii fungaemia in an immunocompetent polytrauma patient who received multiple antibiotics

Ding CH, Khaithir TMN, Wahab AA, Faiz MA, Saarah WR

Malays J Pathol, 2020 Aug;42(2):293-296.
PMID: 32860385

Trichosporon asahii is a yeast-like fungus that is emerging as an important cause of invasive infections in tertiary medical centres. A 58-year-old Chinese man with no known medical illnesses presented with liver lacerations and multiple fractures following an alleged 12-foot fall at a construction site. The gravity of his injuries and poor haemodynamic status necessitated an intensive care unit (ICU) admission, during which several febrile episodes were detected and multiple antibiotics were administered. After being in the ICU for at least two weeks, a urease-positive yeast was isolated from the patient's blood. The yeast formed dry, fuzzy and wrinkled white colonies on Sabouraud dextrose agar following prolonged incubation, and produced blastoconidia, true hyphae, pseudohyphae and arthroconidia on slide culture. It was identified biochemically by the ID 32 C kit as T. asahii. The yeast had elevated minimal inhibitory concentration (MIC) values to fluconazole, amphotericin B, flucytosine and all echinocandins tested. In view of this, the patient was treated with voriconazole and was successfully transferred to the general medical ward.

Matched MeSH terms: Multiple Trauma/drug therapy; Fungemia/drug therapy; Trichosporonosis/drug therapy*
Fulltext Enhanced efficacy of sequential administration of Albendazole for the clearance of Wuchereria bancrofti infection: Double blind RCT

De Britto RL, Vanamail P, Sankari T, Vijayalakshmi G, Das LK, Pani SP

Trop Biomed, 2015 Jun;32(2):198-209.
PMID: 26691247 MyJurnal

Till today, there is no effective treatment protocol for the complete clearance of Wuchereria bancrofti (W.b) infection that causes secondary lymphoedema. In a double blind randomized control trial (RCT), 146 asymptomatic W. b infected individuals were randomly assigned to one of the four regimens for 12 days, DEC 300 mg + Doxycycline 100 mg coadministration or DEC 300 mg + Albendazole 400 mg co-administration or DEC 300 mg + Albendazole 400 mg sequential administration or control regimen DEC 300 mg and were followed up at 13, 26 and 52 weeks post-treatment for the clearance of infection. At intake, there was no significant variation in mf counts (F(3,137)=0.044; P=0.988) and antigen levels (F(3,137)=1.433; P=0.236) between the regimens. Primary outcome analysis showed that DEC + Albendazole sequential administration has an enhanced efficacy over DEC + Albendazole co-administration (80.6 Vs 64.7%), and this regimen is significantly different when compared to DEC + doxycycline co-administration and control (P<0.05), in clearing microfilaria in 13 weeks. Secondary outcome analysis showed that, all the trial regimens were comparable to control regimen in clearing antigen (F(3, 109)=0.405; P=0.750). Therefore, DEC + Albendazole sequential administration appears to be a better option for rapid clearance of W. b microfilariae in 13 weeks time. (Clinical trials.gov identifier - NCT02005653).

Matched MeSH terms: Drug Therapy, Combination/methods; Filariasis/drug therapy*
Fulltext Antimalarial properties of Goniothalamin in combination with chloroquine against Plasmodium yoelii and Plasmodium berghei growth in mice

Mohd Ridzuan MA, Ruenruetai U, Noor Rain A, Khozirah S, Zakiah I

Trop Biomed, 2006 Dec;23(2):140-6.
PMID: 17322815 MyJurnal

Malaria is a disease which is still endemic and has become a disastrous scourge because of the emergence of antimalarial drug resistant Plasmodium falciparum. A new approach in addressing this is in developing a combination drug. This study is to show the enhancement of antimalarial properties, when single compound, goniothalamin combine with standard drug, chloroquine. Based on 4 Day Test, percentage of parasite growth on treated infected mice were determined. Oral treatment with 1 mg/kg BW of chloroquine on experimental mice suppressed 70% and 76.7% of both Plasmodium yoelii and Plasmodium berghei, respectively. The infection of P. berghei in mice was inhibited less than 50% by goniothalamin individual treatment at all doses in this study. About 27.8% and 18.5% inhibition of infection were observed in P. yoelii infected mice treated with 30 mg/kg and 60 mg/kg of goniothalamin respectively and the suppression exceed more than 50% at higher doses (90 and 120 mg/kg). Combination of 1 mg/kg chloroquine with either 30 mg/kg or 60 mg/kg of goniothalamin decreased the parasitemia of P. yoelii infected mice more than 90% and prolong the survival up to 100% after treatment. Similar treatment to P. berghei infected mice only shows about 60% reduction of parasitemia. The study findings showed that antimalarial property of goniothalamin was enhanced by combination with chloroquine at lower dose of each drug.

Matched MeSH terms: Drug Therapy, Combination; Malaria/drug therapy*; Parasitemia/drug therapy
Fulltext Anti-Diabetic Activity and Metabolic Changes Induced by Andrographis paniculata Plant Extract in Obese Diabetic Rats

Akhtar MT, Bin Mohd Sarib MS, Ismail IS, Abas F, Ismail A, Lajis NH, et al.

Molecules, 2016 Aug 09;21(8).
PMID: 27517894 DOI: 10.3390/molecules21081026

Andrographis paniculata is an annual herb and widely cultivated in Southeast Asian countries for its medicinal use. In recent investigations, A. paniculata was found to be effective against Type 1 diabetes mellitus (Type 1 DM). Here, we used a non-genetic out-bred Sprague-Dawley rat model to test the antidiabetic activity of A. paniculata against Type 2 diabetes mellitus (Type 2 DM). Proton Nuclear Magnetic Resonance (¹H-NMR) spectroscopy in combination with multivariate data analyses was used to evaluate the A. paniculata and metformin induced metabolic effects on the obese and obese-diabetic (obdb) rat models. Compared to the normal rats, high levels of creatinine, lactate, and allantoin were found in the urine of obese rats, whereas, obese-diabetic rats were marked by high glucose, choline and taurine levels, and low lactate, formate, creatinine, citrate, 2-oxoglutarate, succinate, dimethylamine, acetoacetate, acetate, allantoin and hippurate levels. Treatment of A. paniculata leaf water extract was found to be quite effective in restoring the disturbed metabolic profile of obdb rats back towards normal conditions. Thisstudy shows the anti-diabetic potential of A. paniculata plant extract and strengthens the idea of using this plant against the diabetes. Further classical genetic methods and state of the art molecular techniques could provide insights into the molecular mechanisms involved in the pathogenesis of diabetes mellitus and anti-diabetic effects of A. paniculata water extract.

Matched MeSH terms: Diabetes Mellitus, Experimental/drug therapy*; Diabetes Mellitus, Type 2/drug therapy*; Obesity/drug therapy*
Antithrombotic effects of hydroxychloroquine in a pregnant patient with Antiphospholipid syndrome and recurrent venous thromboembolism

Gan SP, Ong SG

Med J Malaysia, 2017 04;72(2):124-125.
PMID: 28473677 MyJurnal

A pregnant woman with antiphospholipid syndrome presented with repeated venous thromboembolism (VTE) in the first and second trimesters of pregnancy despite receiving combination therapy with low-molecular-weight heparin and aspirin. The addition of hydroxychloroquine prevented further VTE recurrence, thus demonstrating its potential antithrombotic effects.

Matched MeSH terms: Pregnancy Complications/drug therapy*; Pregnancy Complications, Cardiovascular/drug therapy*; Antiphospholipid Syndrome/drug therapy
Painful Rashes on the Palms and Soles

Bhullar M, Bhullar A, Arachchi NJ

Ann Acad Med Singap, 2016 Oct;45(10):479-480.
PMID: 27832225
Matched MeSH terms: Carcinoma, Hepatocellular/drug therapy*; Liver Neoplasms/drug therapy*; Neoplasms, Multiple Primary/drug therapy*
Single-dose and short course regimens of metronidazole in the treatment of amoebiasis in Malaysia

O'Holohan DR, Hugoe-Matthews J

Ann Trop Med Parasitol, 1972 Jun;66(2):181-6.
PMID: 4338870
Matched MeSH terms: Amebiasis/drug therapy*; Dysentery, Amebic/drug therapy; Intestinal Diseases, Parasitic/drug therapy
Appetite stimulation and weight gain with cyproheptadine (periactin) in tuberculosis patients (double-blind clinical study)

Rahman KM

Med J Malaysia, 1975 Jun;29(4):270-4.
PMID: 1105100
Matched MeSH terms: Anorexia/drug therapy*; Feeding and Eating Disorders/drug therapy*; Tuberculosis, Pulmonary/drug therapy
Autism and trichotillomania in an adolescent boy

Masiran R

BMJ Case Rep, 2018 Sep 05;2018.
PMID: 30185454 DOI: 10.1136/bcr-2018-226270

An adolescent with autism spectrum disorder and improperly treated attention deficit hyperactivity disorder presented with recurrent hair pulling. Treatment with selective serotonin reuptake inhibitor and stimulant improved these conditions.

Matched MeSH terms: Attention Deficit Disorder with Hyperactivity/drug therapy*; Autistic Disorder/drug therapy*; Trichotillomania/drug therapy*
Unusual ocular manifestations following viper bite

Aye MTH, Naing T, Myint KT

BMJ Case Rep, 2018 Sep 05;2018.
PMID: 30185451 DOI: 10.1136/bcr-2018-225040

We report a case of a 70-year-old farmer admitted for viper bite who presented with bilateral hyphema and angle closure attack. He was managed conservatively with topical steroids and cycloplegics. He responded well and was discharged after 2 weeks.

Matched MeSH terms: Hyphema/drug therapy; Snake Bites/drug therapy; Glaucoma, Angle-Closure/drug therapy
In vivo antitumour properties of tribenzyltin carboxylates in a 4T1 murine metastatic mammary tumour model: Enhanced efficacy by PLGA nanoparticles

Anasamy T, Chee CF, Kiew LV, Chung LY

Eur J Pharm Sci, 2020 Jan 15;142:105140.
PMID: 31704345 DOI: 10.1016/j.ejps.2019.105140

This study reports the in vivo performance of two tribenzyltin carboxylate complexes, tri(4-fluorobenzyl)tin[(N,N-diisopropylcarbamothioyl)sulfanyl]acetate (C1) and tribenzyltin isonicotinate (C9), in their native form as well as in a poly(lactic-co-glycolic acid) (PLGA)-based nanoformulation, to assess their potential to be translated into clinically useful agents. In a 4T1 murine metastatic mammary tumour model, single intravenous administration of C1 (2.7 mg/kg) and C9 (2.1 mg/kg; 2.1 mg/kg C9 is equivalent to 2.7 mg/kg C1) induced greater tumour growth delay than cisplatin and doxorubicin at equivalent doses, while a double-dose regimen demonstrated a much greater tumour growth delay than the single-dose treated groups. To improve the efficacy of the complexes in vivo, C1 and C9 were further integrated into PLGA nanoparticles to yield nanosized PLGA-C1 (183.7 ± 0.8 nm) and PLGA-C9 (163.2 ± 1.2 nm), respectively. Single intravenous administration of PLGA-C1 (2.7 mg C1 equivalent/kg) and PLGA-C9 (2.1 mg C9 equivalent/kg) induced greater tumour growth delay (33% reduction in the area under curve compared to that of free C1 and C9). Multiple-dose administration of PLGA-C1 (5.4 mg C1 equivalent/kg) and PLGA-C9 (4.2 mg C9 equivalent/kg) induced tumour growth suppression at the end of the study (21.7 and 34.6% reduction relative to the size on day 1 for the double-dose regimen; 73.5 and 79.0% reduction relative to the size on day 1 for the triple-dose regimen, respectively). Such tumour growth suppression was not observed in mice receiving multiple-dose regimens of free C1 and C9. Histopathological analysis revealed that metastasis to the lung and liver was inhibited in mice receiving PLGA-C1 and PLGA-C9. The current study has demonstrated the improved in vivo antitumour efficacies of C1 and C9 compared with conventional chemotherapy drugs and the enhancement of the efficacies of these agents via a robust PLGA-based nanoformulation and multiple-drug administration approach.

Matched MeSH terms: Liver Neoplasms/drug therapy; Lung Neoplasms/drug therapy; Mammary Neoplasms, Animal/drug therapy*
Fulltext Onychomycosis: An Updated Review

Leung AKC, Lam JM, Leong KF, Hon KL, Barankin B, Leung AAM, et al.

Recent Pat Inflamm Allergy Drug Discov, 2020;14(1):32-45.
PMID: 31738146 DOI: 10.2174/1872213X13666191026090713

BACKGROUND: Onychomycosis is a common fungal infection of the nail.
OBJECTIVE: The study aimed to provide an update on the evaluation, diagnosis, and treatment of onychomycosis.
METHODS: A PubMed search was completed in Clinical Queries using the key term "onychomycosis". The search was conducted in May 2019. The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews published within the past 20 years. The search was restricted to English literature. Patents were searched using the key term "onychomycosis" in www.freepatentsonline.com.
RESULTS: Onychomycosis is a fungal infection of the nail unit. Approximately 90% of toenail and 75% of fingernail onychomycosis are caused by dermatophytes, notably Trichophyton mentagrophytes and Trichophyton rubrum. Clinical manifestations include discoloration of the nail, subungual hyperkeratosis, onycholysis, and onychauxis. The diagnosis can be confirmed by direct microscopic examination with a potassium hydroxide wet-mount preparation, histopathologic examination of the trimmed affected nail plate with a periodic-acid-Schiff stain, fungal culture, or polymerase chain reaction assays. Laboratory confirmation of onychomycosis before beginning a treatment regimen should be considered. Currently, oral terbinafine is the treatment of choice, followed by oral itraconazole. In general, topical monotherapy can be considered for mild to moderate onychomycosis and is a therapeutic option when oral antifungal agents are contraindicated or cannot be tolerated. Recent patents related to the management of onychomycosis are also discussed.
CONCLUSION: Oral antifungal therapies are effective, but significant adverse effects limit their use. Although topical antifungal therapies have minimal adverse events, they are less effective than oral antifungal therapies, due to poor nail penetration. Therefore, there is a need for exploring more effective and/or alternative treatment modalities for the treatment of onychomycosis which are safer and more effective.

Matched MeSH terms: Foot Dermatoses/drug therapy; Hand Dermatoses/drug therapy; Onychomycosis/drug therapy*
Fulltext Surveillance of adverse events in the treatment of drug-resistant tuberculosis: A global feasibility study

Akkerman O, Aleksa A, Alffenaar JW, Al-Marzouqi NH, Arias-Guillén M, Belilovski E, et al.

Int J Infect Dis, 2019 Jun;83:72-76.
PMID: 30953827 DOI: 10.1016/j.ijid.2019.03.036

The World Health Organization launched a global initiative, known as aDSM (active TB drug safety monitoring and management) to better describe the safety profile of new treatment regimens for drug-resistant tuberculosis (TB) in real-world settings. However, comprehensive surveillance is difficult to implement in several countries. The aim of the aDSM project is to demonstrate the feasibility of implementing national aDSM registers and to describe the type and the frequency of adverse events (AEs) associated with exposure to the new anti-TB drugs. Following a pilot study carried out in 2016, official involvement of TB reference centres/countries into the project was sought and cases treated with bedaquiline- and/or delamanid-containing regimens were consecutively recruited. AEs were prospectively collected ensuring potential attribution of the AE to a specific drug based on its known safety profile. A total of 309 cases were fully reported from 41 centres in 27 countries (65% males; 268 treated with bedaquiline, 20 with delamanid, and 21 with both drugs) out of an estimated 781 cases the participating countries had committed to report by the first quarter of 2019.

Matched MeSH terms: Drug Therapy, Combination; Tuberculosis/drug therapy; Tuberculosis, Multidrug-Resistant/drug therapy*

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