31 research outputs found

    Suppression of ERK1/2 and hypoxia pathways by four Phyllanthus species inhibits metastasis of human breast cancer cells

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    Chemotherapies remain far from ideal due to drug resistance; therefore, novel chemotherapeutic agents with higher effectiveness are crucial. The extracts of four Phyllanthus species, namely Phyllanthus niruri, Phyllanthus urinaria, Phyllanthus watsonii, and Phyllanthus amarus, were shown to induce apoptosis and inhibit metastasis of breast carcinoma cells (MCF-7). The main objective of this study was to determine the pathways utilized by these four Phyllanthus species to exert anti-metastatic activities. A cancer 10-pathway reporter was used to investigate the pathways affected by the four Phyllanthus species. Results indicated that these Phyllanthus species suppressed breast carcinoma metastasis and proliferation by suppressing matrix metalloprotein 2 and 9 expression via inhibition of the extracellular signal-related kinase (ERK) pathway. Additionally, inhibition of hypoxia-inducible factor 1-α in the hypoxia pathway caused reduced vascular endothelial growth factor and inducible nitric oxide synthase expression, resulting in anti-angiogenic effects and eventually anti-metastasis. Two-dimensional gel electrophoresis identified numerous proteins suppressed by these Phyllanthus species, including invasion proteins, anti-apoptotic protein, protein-synthesis proteins, angiogenic and mobility proteins, and various glycolytic enzymes. Our results indicated that ERK and hypoxia pathways are the most likely targets of the four Phyllanthus species for the inhibition of MCF-7 metastasis

    Quality of life index in patients with vitiligo

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    Objective: To ascertain the quality of life (QoL) impairment among the Pakistani population with vitiligo and to determine the relationship between sociodemographic and clinical characteristics. Study design: Cross-sectional study. Place and Duration of the Study: Dermatology Outpatients at the Aga Khan University in collaboration with outpatients of seven tertiary care hospitals of Sindh, Punjab, KPK, Balochistan, and AJK to collect data from March 2015 to April 2019. Methodology: All clinically diagnosed patients of vitiligo, who signed consent and assent forms, were included in the study. A validated 25-item, QoL scale for vitiligo was used. Socio-economic status of the patients, clinical assessment of the disease and patients\u27 engagement in social and domestic lives was noted. Results: Five hundred and seventy-three patients were enrolled in the study, having mean age 29.8 ± 16.2 years. In 306 (53.4%) males and 267 (46.65%) females; 21.8% were below 18 years. Mean vitiligo QoL index was 38.4 ± 11.8. Patients of vitiligo with disease duration 5-10 years, those affected on exposed parts, more than five body sites, rapidly progressing disease and of female gender had a higher impairment of quality of life. These scores were found significantly higher as compared to other levels of these parameters (p\u3c0.05). Conclusion: Patients with vitiligo experience low self-esteem. The disease adversely affects their quality of life. The authors recommend the use of disease-specific instruments to assess the quality of life which enables the treating physician to devise best possible management plan individuall

    Relapse of chronic melioidosis in a paediatric cystic fibrosis patient: first case report from Malaysia

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    Abstract Background Burkholderia pseudomallei is the causative agent of melioidosis, which is a potentially life threatening disease endemic in Southeast Asian countries. In Malaysia, cystic fibrosis (CF) is an uncommon condition. The association between CF and B.pseudomallei infections has been reported previously. However, this is the first case report of a pediatric melioidosis relapse and co-infection with other Gram-negative bacteria in Malaysia. Case presentation A 14-year-old Chinese Malaysian boy presented with a history of recurrent pneumonia, poor growth and steatorrhoea since childhood, and was diagnosed with CF. B. pseudomallei was cultured from his sputum during three different admissions between 2013 and 2016. However, the patient succumbed to end stage of respiratory failure in 2017 despite antibiotics treatment against B.pseudomallei. The isolates were compared using multilocus-sequence typing and repetitive-element polymerase chain reaction (PCR), and confirmed that two of the isolates were of same sequence type, which may indicate relapse. Conclusions CF patients should be aware of melioidosis in endemic regions, as it is an emerging infectious disease, especially when persistent or recurrent respiratory symptoms and signs of infection occur. The high prevalence rates of melioidosis in Malaysia warrants better management options to improve quality of life, and life expectancy in patients with CF. Travel activities to endemic regions should also be given more consideration, as this would be crucial to identify and initiate appropriate empiric treatment

    Pitfalls in diagnosis and management of suspected urinary tract infection in an urban tropical primary care setting

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    Introduction: Diagnosis and management of urinary tract infection (UTI) are complex, and do not always follow guidelines. The aim of this study was to determine adherence to the 2014 Malaysian Ministry of Health guidelines for managing suspected UTI in a Malaysian primary care setting. Methodology: We retrospectively reviewed computerized medical records of adults with suspected UTI between July-December 2016. Excluded were consultations misclassified by the search engine, duplicated records of the same patient, consultations for follow-up of suspected UTI, patients who were pregnant, catheterised, or who had a renal transplant. Records were reviewed by two primary care physicians and a clinical microbiologist. Results: From 852 records, 366 consultations were a fresh episode of possible UTI. Most subjects were female (78.2%) with median age of 61.5 years. The major co-morbidities were hypertension (37.1%), prostatic enlargement in males (35.5%) and impaired renal function (31.1%). Symptoms were reported in 349 (95.4%) consultations. Antibiotics were prescribed in 307 (83.9%) consultations, which was appropriate in 227/307 (73.9%), where the subject had at least one symptom, and leucocytes were raised in urine full examination and microscopic examination (UFEME). In 73 (23.8%) consultations antibiotics were prescribed inappropriately, as the subjects were asymptomatic (14,4.6%), urine was clear (17,5.5%), or UFEME did not show raised leucocytes (42,13.7%). In 7 (2.3%) consultations appropriateness of antibiotics could not be determined as UFEME was not available. Conclusion: Several pitfalls contributed to suboptimal adherence to guidelines for diagnosis and management of suspected UTI. This illustrates the complexity of managing suspected UTI in older subjects with multiple co-morbidities. © 2019 Jackson et al

    Knowledge, perception, and antibiotic prescribing practice in the intensive care unit: findings from the Malaysian public setting

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    Introduction:\ua0Approach to managing infection in the intensive care unit (ICU) often varies between institutions and not many readily adapt to available local guidelines despite it was constructed to suite local clinical scenario. Malaysia already has two published guidelines on managing infection in the ICU but data on its compliance are largely unknown.\ua0Objectives:\ua0A cross-sectional survey was carried out and sent to a total of 868 specialists working primarily in the ICU. The aim of this study was to explore knowledge, perception, and the antibiotic prescribing practice among specialists and advanced trainees in Malaysian ICU.\ua0Materials and Methods:\ua0A cross-sectional survey was used, consisted of three sections: knowledge, perception, and antibiotic prescribing practice in ICU. Three case vignettes on hospital-acquired pneumonia (HAP), infected necrotizing pancreatitis (INP), and catheter-related bloodstream infection (CRBSI) were used to explore antibiotic prescribing practice.\ua0Results:\ua0A total of 868 eligible subjects were approached with 104 responded to the survey. Three hundred eighty-nine antibiotics were chosen from seven different classes in the case vignettes. All respondents acknowledged the importance of pharmacokinetic/pharmacodynamic (PK/PD) in antibiotic optimization and majority (97.2%) perceived that current dosing is inadequate to achieve optimal PK/PD target in ICU patients. Majority (85.6%) believed that antibiotic dose should be streamlined to the organisms’ minimum inhibitory concentration (MIC). In terms of knowledge, only 64.4% provided the correct correlations between antibiotics and their respective PK/PD targets. Compliance rates in terms of antibiotic choices were at 79.8%, 77.8%, and 27.9% for HAI, INP, and CRBSI, respectively.\ua0Conclusion:\ua0Malaysian physicians are receptive to use PK/PD approach to optimize antibiotic dosing in ICU patients. Nonetheless, there are still gaps in the knowledge of antibiotic PK/PD as well as its application in the critically ill, especially for β-lactams
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