Displaying publications 1 - 20 of 10657 in total

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  1. Castaño-Rodríguez N, Kaakoush NO, Pardo AL, Goh KL, Fock KM, Mitchell HM
    Hum Immunol, 2014 Aug;75(8):808-15.
    PMID: 24929142 DOI: 10.1016/j.humimm.2014.06.001
    Gastric cancer (GC) is a progressive process initiated by Helicobacter pylori-induced inflammation. Initial recognition of H. pylori involves Toll-like receptors (TLRs), central molecules in the host inflammatory response. Here, we investigated the association between novel polymorphisms in genes involved in the TLR signalling pathway, including TLR2, TLR4, LBP, MD-2, CD14 and TIRAP, and risk of H. pylori infection and related GC.
    Matched MeSH terms: Middle Aged
  2. Ji L, Han P, Liu Y, Yang G, Dieu Van NK, Vijapurkar U, et al.
    Diabetes Obes Metab, 2015 Jan;17(1):23-31.
    PMID: 25175734 DOI: 10.1111/dom.12385
    To evaluate the efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 inhibitor, in Asian patients with type 2 diabetes mellitus (T2DM) inadequately controlled by metformin or metformin in combination with sulphonylurea.
    Matched MeSH terms: Middle Aged
  3. Au A, Aziz Baba A, Goh AS, Wahid Fadilah SA, Teh A, Rosline H, et al.
    Biomed Pharmacother, 2014 Apr;68(3):343-9.
    PMID: 24581936 DOI: 10.1016/j.biopha.2014.01.009
    The introduction and success of imatinib mesylate (IM) has become a paradigm shift in chronic myeloid leukemia (CML) treatment. However, the high efficacy of IM has been hampered by the issue of clinical resistance that might due to pharmacogenetic variability. In the current study, the contribution of three common single nucleotide polymorphisms (SNPs) of ABCB1 (T1236C, G2677T/A and C3435T) and two SNPs of ABCG2 (G34A and C421A) genes in mediating resistance and/or good response among 215 CML patients on IM therapy were investigated. Among these patients, the frequency distribution of ABCG2 421 CC, CA and AA genotypes were significantly different between IM good response and resistant groups (P=0.01). Resistance was significantly associated with patients who had homozygous ABCB1 1236 CC genotype with OR 2.79 (95%CI: 1.217-6.374, P=0.01). For ABCB1 G2677T/A polymorphism, a better complete cytogenetic remission was observed for patients with variant TT/AT/AA genotype, compared to other genotype groups (OR=0.48, 95%CI: 0.239-0.957, P=0.03). Haplotype analysis revealed that ABCB1 haplotypes (C1236G2677C3435) was statistically linked to higher risk to IM resistance (25.8% vs. 17.4%, P=0.04), while ABCG2 diplotype A34A421 was significantly correlated with IM good response (9.1% vs. 3.9%, P=0.03). In addition, genotypic variant in ABCG2 421C>A was associated with a major molecular response (MMR) (OR=2.20, 95%CI: 1.273-3.811, P=0.004), whereas ABCB1 2677G>T/A variant was associated with a significantly lower molecular response (OR=0.49, 95%CI: 0.248-0.974, P=0.04). However, there was no significant correlation of these SNPs with IM intolerance and IM induced hepatotoxicity. Our results suggest the usefulness of genotyping of these single nucleotide polymorphisms in predicting IM response among CML patients.
    Matched MeSH terms: Middle Aged
  4. Wong KK, Gascoyne DM, Brown PJ, Soilleux EJ, Snell C, Chen H, et al.
    Leukemia, 2014 Feb;28(2):362-72.
    PMID: 23884370 DOI: 10.1038/leu.2013.224
    We previously identified autoantibodies to the endocytic-associated protein Huntingtin-interacting protein 1-related (HIP1R) in diffuse large B-cell lymphoma (DLBCL) patients. HIP1R regulates internalization of cell surface receptors via endocytosis, a process relevant to many therapeutic strategies including CD20 targeting with rituximab. In this study, we characterized HIP1R expression patterns, investigated a mechanism of transcriptional regulation and its clinical relevance in DLBCL patients treated with immunochemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone, R-CHOP). HIP1R was preferentially expressed in germinal center B-cell-like DLBCL (P<0.0001) and inversely correlated with the activated B-cell-like DLBCL (ABC-DLBCL) associated transcription factor, Forkhead box P1 (FOXP1). HIP1R was confirmed as a direct FOXP1 target gene in ABC-DLBCL by FOXP1-targeted silencing and chromatin immunoprecipitation. Lower HIP1R protein expression (≤ 10% tumoral positivity) significantly correlated with inferior overall survival (OS, P=0.0003) and progression-free survival (PFS, P=0.0148) in R-CHOP-treated DLBCL patients (n=157). Reciprocal expression with ≥ 70% FOXP1 positivity defined FOXP1(hi)/HIP1R(lo) patients with particularly poor outcome (OS, P=0.0001; PFS, P=0.0016). In an independent R-CHOP-treated DLBCL (n=233) microarray data set, patients with transcript expression in lower quartile HIP1R and FOXP1(hi)/HIP1R(lo) subgroups exhibited worse OS, P=0.0044 and P=0.0004, respectively. HIP1R repression by FOXP1 is strongly associated with poor outcome, thus further understanding of FOXP1-HIP1R and/or endocytic signaling pathways might give rise to novel therapeutic options for DLBCL.
    Matched MeSH terms: Middle Aged
  5. Khalilpour A, Santhanam A, Wei LC, Saadatnia G, Velusamy N, Osman S, et al.
    Asian Pac J Cancer Prev, 2013;14(3):1635-42.
    PMID: 23679248
    Helicobacter pylori antigen was prepared from an isolate from a patient with a duodenal ulcer. Serum samples were obtained from culture-positive H. pylori infected patients with duodenal ulcers, gastric ulcers and gastritis (n=30). As controls, three kinds of sera without detectable H. pylori IgG antibodies were used: 30 from healthy individuals without history of gastric disorders, 30 from patients who were seen in the endoscopy clinic but were H. pylori culture negative and 30 from people with other diseases. OFF-GEL electrophoresis, SDS-PAGE and Western blots of individual serum samples were used to identify protein bands with good sensitivity and specificity when probed with the above sera and HRP-conjugated anti-human IgG. Four H. pylori protein bands showed good (≥ 70%) sensitivity and high specificity (98-100%) towards anti-Helicobacter IgG antibody in culture- positive patients sera and control sera, respectively. The identities of the antigenic proteins were elucidated by mass spectrometry. The relative molecular weights and the identities of the proteins, based on MALDI TOF/ TOF, were as follows: CagI (25 kDa), urease G accessory protein (25 kDa), UreB (63 kDa) and proline/pyrroline- 5-carboxylate dehydrogenase (118 KDa). These identified proteins, singly and/or in combinations, may be useful for diagnosis of H. pylori infection in patients.
    Matched MeSH terms: Middle Aged
  6. Lim-Abrahan MA, Jain AB, Bebakar WM, Seah D, Soewondo P
    Diabetes Res Clin Pract, 2013 Apr;100 Suppl 1:S3-9.
    PMID: 23647715 DOI: 10.1016/S0168-8227(13)70003-2
    AIM:
    To determine the safety and effectiveness of biphasic insulin aspart 30 (BIAsp 30) in the ASEAN cohort of the A₁chieve study.

    METHODS:
    Type 2 diabetes patients from Indonesia, Malaysia, Philippines and Singapore prescribed BIAsp 30 therapy were included. The primary outcome was evaluation of serious adverse drug reactions including major hypoglycaemia over 24 weeks. Secondary outcomes were changes in hypoglycaemic events, serious adverse events (SAEs) and effectiveness parameters.

    RESULTS:
    This sub-analysis included 2798 patients (insulin-naive, 1903; insulin-experienced, 895) with mean age ± SD, 55.3 ± 10.8 years, BMI, 24.9 ± 4.6 kg/m(2) and diabetes duration, 7.5 ± 5.9 years. Baseline HbA1c in the entire cohort was poor (9.9%, 85 mmol/mol). A total of 15 SAEs were reported in 7 insulin-experienced patients (1 moderate event was related to BIAsp 30). Overall hypoglycaemia at Week 24 was 0.88 events/patient-year compared to 1.71 events/patient-year reported at baseline (change in proportion of patients affected, p < 0.0001). No major hypoglycaemia was reported at Week 24. BIAsp 30 significantly improved glucose control (HbA1c, fasting plasma glucose and postprandial plasma glucose, p < 0.001) at Week 24. The proportion of patients achieving HbA1c <7.0% at Week 24 was 35.3% compared to 3.5% at baseline. The lipid profile and systolic blood pressure also improved significantly (p < 0.001). Quality of life was positively impacted (mean change in visual analogue scores from EQ-5D = 10.6 ± 13.8 points, p < 0.001).

    CONCLUSION:
    BIAsp 30 was well-tolerated and improved glucose control while decreasing the risk of hypoglycaemia.
    Matched MeSH terms: Middle Aged
  7. Hussein Z, Lim-Abrahan MA, Jain AB, Goh SY, Soewondo P
    Diabetes Res Clin Pract, 2013 Apr;100 Suppl 1:S24-9.
    PMID: 23647714 DOI: 10.1016/S0168-8227(13)70006-8
    Aim: To evaluate the safety and effectiveness of biphasic insulin aspart 30 (BIAsp 30) in ASEAN type 2 diabetes (T2D) patients switched from biphasic human insulin (BHI) in the non-interventional 24-week A₁chieve study.

    Methods: Indonesian, Malaysian, Filipino and Singaporean patients switched from BHI to BIAsp 30 at their physicians' discretion were included. The incidence of serious adverse drug reactions (SADRs), including major hypoglycaemia was the primary endpoint. Changes in hypoglycaemia, glycated haemoglobin A1c (HbA1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPPG), lipids, body weight and systolic blood pressure were also evaluated. Quality of life (QoL) was measured using the EQ-5D questionnaire.

    Results: For the 465 patients included (mean ± SD age: 56 ± 10.3 years, diabetes duration: 9.7 ± 7.1 years, baseline HbA1c: 9.4 ± 1.8%), the mean pre-study BHI dose was 0.62 ± 0.28 IU/kg and 63.4% were dosing BHI twice daily (bid). The mean baseline BIAsp 30 dose was 0.65 ± 0.27 U/kg, titrated up to 0.71 ± 0.28 U/kg over 24 weeks, and most patients continued bid dosing. No SADRs or major hypoglycaemic episodes were reported. The proportion of patients reporting overall hypoglycaemia decreased significantly from 10.8% at baseline to 3.4% at Week 24 (p < 0.0001). Significant improvements in glycaemic control were noted (HbA1c: -1.4 ± 1.7%, FPG: -56.7 ± 72.5 mg/dL, post-breakfast PPPG: -84.8 ± 82.8 mg/dL, p < 0.001). Mean QoL improved by +6.6 ± 14.6 points (p < 0.001).

    Conclusion: BIAsp 30 was well-tolerated and significantly increased glycaemic control in this ASEAN subgroup poorly controlled on BHI.
    Matched MeSH terms: Middle Aged
  8. Bebakar WM, Lim-Abrahan MA, Jain AB, Seah D, Soewondo P
    Diabetes Res Clin Pract, 2013 Apr;100 Suppl 1:S17-23.
    PMID: 23647713 DOI: 10.1016/S0168-8227(13)70005-6
    AIM:
    To examine the clinical safety and effectiveness of insulin aspart (IAsp) therapy in type 2 diabetes (T2D) patients from the ASEAN cohort of the international, 24-week, non-interventional A₁chieve study.

    METHODS:
    T2D patients from Indonesia, Malaysia, Philippines and Singapore, who started IAsp therapy with or without oral glucose-lowering drugs, were included. The primary endpoint was the incidence of serious adverse drug reactions (SADRs), including major hypoglycaemic events. Secondary endpoints included hypoglycaemia, glycated haemoglobin A1c [HbA1c], fasting plasma glucose [FPG], postprandial plasma glucose [PPPG], systolic blood pressure [SBP], body weight and lipids. Quality of life (QoL) was assessed using the EQ-5D questionnaire.

    RESULTS:
    Overall, 312 T2D patients (222 insulin-naive and 90 insulin-experienced) with a mean ± SD age of 56.6 ± 11.2 years, BMI of 24.2 ± 3.9 kg/m(2) and diabetes duration of 7.0 ± 5.7 years were included. The mean daily IAsp dose was 0.51 ± 0.31 U/kg at baseline titrated up to 0.60 ± 0.29 U/kg at Week 24. No SADRs or major hypoglycaemic events were reported in the entire subgroup. The proportion of patients who reported overall hypoglycaemia decreased from baseline to Week 24 (7.1% vs. 0.3%, p < 0.0001). The mean HbA1c improved from 9.5 ± 1.6% at baseline to 7.6 ± 1.3% after 24 weeks (p < 0.001). The mean FPG, post-breakfast PPPG and SBP also improved (p < 0.001). Health-related QoL scores increased in the entire subgroup (mean increase: 9.8 ± 14.6 points, p < 0.001).

    CONCLUSIONS:
    Starting IAsp therapy was well-tolerated and was associated with significantly improved overall glycaemic control in the ASEAN cohort.
    Matched MeSH terms: Middle Aged
  9. Soewondo P, Mohamed M, Jain AB, Sy RA, Khoo CM
    Diabetes Res Clin Pract, 2013 Apr;100 Suppl 1:S10-6.
    PMID: 23647712 DOI: 10.1016/S0168-8227(13)70004-4
    AIM:
    To determine the safety and effectiveness of insulin detemir (IDet) in type 2 diabetes patients from the ASEAN cohort of the A1chieve study.

    METHODS:
    Patients from Indonesia, Malaysia, Philippines and Singapore prescribed IDet at the discretion of their physicians were included. The primary outcome was the incidence of serious adverse drug reactions including major hypoglycaemia over 24 weeks. Secondary endpoints included changes in the frequency of hypoglycaemia, serious adverse events and effectiveness assessments.

    RESULTS:
    This sub-analysis included 1540 patients (insulin-naive, 1239; insulin-experienced, 301) with mean age ± SD 56.4 ± 10.9 years, BMI 25.4 ± 4.6 kg/m(2) and diabetes duration 6.9 ± 5.3 years. Insulin-naive patients received a baseline IDet dose of 0.24 ± 0.11 U/kg titrated up to 0.37 ± 0.21 U/kg by Week 24. The pre-study insulin dose in insulin-experienced patients was 0.41 ± 0.25 U/kg and baseline IDet dose was 0.31 ± 0.24 U/kg titrated up to 0.40 ± 0.20 U/kg by Week 24. Overall hypoglycaemia decreased from 1.73 to 0.46 events/patient-year from baseline to Week 24 (change in proportion of patients affected, p < 0.0001). At Week 24, 1 major hypoglycaemic event was reported in 1 insulin-experienced patient. IDet significantly improved glucose control (p < 0.001) at Week 24. The lipid profile and systolic blood pressure improved (p < 0.001) and body weight did not change significantly. Quality of life was positively impacted (p < 0.001).

    CONCLUSION:
    IDet was well-tolerated and improved glycaemic control without increasing the risk of hypoglycaemia or weight gain.
    Matched MeSH terms: Middle Aged
  10. Sazlina SG, Mastura I, Ahmad Z, Cheong AT, Adam BM, Jamaiyah H, et al.
    Geriatr Gerontol Int, 2014 Jan;14(1):130-7.
    PMID: 23581598 DOI: 10.1111/ggi.12070
    The aims of the present study were to assess the control of glycemia and other cardiovascular disease risk factors, and the association between age and these controls among older adults with type 2 diabetes in Malaysia.
    Matched MeSH terms: Middle Aged
  11. Menon R, Mohd Noor FS, Draman CR, Seman MR, Ghani AS
    Saudi J Kidney Dis Transpl, 2012 Sep;23(5):1109-14.
    PMID: 22982937 DOI: 10.4103/1319-2442.100972
    Diabetic nephropathy (DN) has become the most common cause of end-stage renal failure. Early referral and specific nephrology treatment could delay the disease progression and should reduce the treatment cost, mortality and morbidity rate in these patients. This is a single-center, retrospective review of all DN patients referred to the nephrology clinic in Hospital Sultan Ahmad Shah, Temerloh, from 2000 to 2009, to study and define the clinical characteristics of DN patients at the time of the referral to the nephrology clinic. A total of 75 patient case records were reviewed. Forty-three (57.3%) of them were males, with a median age of 64.3 ± 8.5 years at the time of referral. Only 14.7% of them had blood pressure lower than 125/75 mmHg. Co-morbid and disease-related complications were also commonly diagnosed and 28.4% (n = 21) had ischemic heart disease, 23% (n = 17) had diabetic retinopathy and 20.3% (n = 15) had diabetic neuropathy. The mean serum creatinine at the time of referral was 339.8 ± 2.3 μmol/L, gylcated hemoglobin A 1c (HbA1C) was 8.1 ± 2.0 %, serum fasting glucose was 9.6 ± 4.7 mmol/L, serum cholesterol was 5.4 ± 1.2 mmol/L and hemoglobin level was 10.6 ± 2.9 g/dL. Although female patients were less frequently seen in the early stages of chronic kidney disease (CKD), they comprised at least 72.7% of CKD stage 5 (male:female; 6:16, P <0.05). Twenty-nine percent (n=22) of them were referred at CKD stage 5, 48% (n=36) were at CKD stage 4, 17.3% (n=13) were at CKD stage 3, 4% (n=3) were at CKD stage 2 and 1.3% (n=1) was at CKD stage 1. Advanced CKD patients were frequently prescribed with more antihypertensives. CKD stage 5 patients were prescribed with two-and-half types of antihypertensive as compared to two types of anti-hypertensive in CKD stage 2 and stage 3. Furthermore, ACE-inhibitors (ACE-I) were less frequently prescribed to them. Only 22.7% (n=5) of CKD stage 5 patients received ACE-I and 30% (n=11) in CKD stage 4 patients as compared to 53.4% (n=7) in CKD patients stage 3. This review shows that DN patients were referred late to the nephrologists and the overall disease management was suboptimal. Antihypertensive requirement was also increased and ACEIs were less frequently prescribed in the advanced diabetic nephropathy patients.
    Study site: Nephrology Clinic, Hospital Sultan Ahmad Shah, Temerloh, Pahang, Malaysia
    Matched MeSH terms: Middle Aged
  12. Zubaidah NH, Azim MI, Osama MH, Harunarashid H, Das S
    Clin Ter, 2012;163(1):27-9.
    PMID: 22362230
    The incidence of infection following TEVAR is low. To the best of our knowledge, this is the first case report of post thoracic endovascular aortic repair (TEVAR) with Streptococcus viridans graft infection. A 54-year-old male underwent TEVAR for dissecting thoracic aneurysm with spinal ischaemia. He had an eventful recovery with prolonged period of stay in intensive care unit. Three months later, he presented with persistent chest discomfort and fever. Computed tomography (CT) of the thorax revealed evidence of graft infection and the blood culture grew Streptococcus viridans. The rarity of TEVAR graft infection due to Streptococcus viridans and its management are being discussed.
    Matched MeSH terms: Middle Aged
  13. Sidi H, Asmidar D, Hod R, Jaafar NR, Guan NC
    Int J Psychiatry Clin Pract, 2012 Mar;16(1):41-7.
    PMID: 22122658 DOI: 10.3109/13651501.2011.617457
    To determine the risk of hypoactive sexual desire (HSD) in depressed female patients treated with selective serotonin reuptake inhibitors, comparing escitalopram and fluoxetine. The associated factors were also examined.
    Matched MeSH terms: Middle Aged
  14. Maha A, Cheong SK, Leong CF, Seow HF
    Malays J Pathol, 2009 Dec;31(2):81-91.
    PMID: 20514850 MyJurnal
    Signal transduction pathways are constitutively expressed in leukaemic cells resulting in aberrant survival of the cells. It is postulated that in cells of chemo-sensitive patients, chemotherapy induces apoptotic signals leading to cell death while survival signals are maintained in cells of chemo-resistant patients. There is very little information currently, on the expression of these mediators in patients immediately after chemotherapy initiation. We examined the expression pattern of proinflammatory cytokines, signaling molecules of the PI3K and MAPK pathways molecules and death receptor, DR5 on paired samples at diagnosis and during chemotherapy in acute myeloid leukaemia patients treated with cytosine arabinoside and daunorubicin. The results were correlated with remission status one month after chemotherapy. We found that in chemo-sensitive patients, chemotherapy significantly increased the percentage of cases expressing TNF-alpha (p = 0.025, n = 9) and IL-6 (p = 0.002, n = 11) compared to chemo-resistant cases. We also observed an increased percentage of chemo-sensitive cases expressing DR5 and phosphorylated p38, and Jnk. Thus, expression of TNF-alpha, IL-6, DR5, phospho-p38 and phospho-Jnk may regulate cell death in chemo-sensitive cases. In contrast, a significantly higher percentage of chemo-resistant cases expressed phospho-Bad (p = 0.027, n = 9). IL-beta and IL-18 were also found to be higher in chemo-resistant cases at diagnosis and during chemotherapy. Thus, expression of various cellular molecules in leukaemic blasts during chemotherapy may be useful in predicting treatment outcome. These cellular molecules may also be potential targets for alternative therapy.
    Matched MeSH terms: Middle Aged
  15. Gan GG, Phipps ME, Lee MM, Lu LS, Subramaniam RY, Bee PC, et al.
    Ann Hematol, 2011 Jun;90(6):635-41.
    PMID: 21110192 DOI: 10.1007/s00277-010-1119-6
    Within the Asian populations, Indian patients had been reported to require higher warfarin dose compared with the Chinese and Malay patients, and this could not entirely be explained by cytochrome P450 (CYP)2C9 gene variants. Genetic variants of vitamin K epoxide oxidase reductase complex subunit 1 (VKORC1) has been well established as one of key determinants in the different responses of warfarin amongst patients. Adult patients who attended an anticoagulation clinic with stable INR were recruited. VKORC1 and CYP2C9 genotype were sequenced, and clinical characteristics were assessed. A total of 91 Malays, 96 Chinese, and 46 Indian patients were recruited. The mean age was 55 years and 51.5% were males. The mean dose of warfarin for all patients was 3.7 mg, and the mean daily dose of warfarin was significantly higher in Indians compared with the Chinese and Malay patients, 4.9 versus 3.5 and 3.3 mg, respectively (p 
    Matched MeSH terms: Middle Aged
  16. Daneshvar C, Davis TM, Cox-Singh J, Rafa'ee MZ, Zakaria SK, Divis PC, et al.
    Clin Infect Dis, 2009 Sep 15;49(6):852-60.
    PMID: 19635025 DOI: 10.1086/605439
    BACKGROUND: Plasmodium knowlesi is increasingly recognized as a cause of human malaria in Southeast Asia but there are no detailed prospective clinical studies of naturally acquired infections.

    METHODS: In a systematic study of the presentation and course of patients with acute P. knowlesi infection, clinical and laboratory data were collected from previously untreated, nonpregnant adults admitted to the hospital with polymerase chain reaction-confirmed acute malaria at Kapit Hospital (Sarawak, Malaysia) from July 2006 through February 2008.

    RESULTS: Of 152 patients recruited, 107 (70%) had P. knowlesi infection, 24 (16%) had Plasmodium falciparum infection, and 21 (14%) had Plasmodium vivax. Patients with P. knowlesi infection presented with a nonspecific febrile illness, had a baseline median parasitemia value at hospital admission of 1387 parasites/microL (interquartile range, 6-222,570 parasites/microL), and all were thrombocytopenic at hospital admission or on the following day. Most (93.5%) of the patients with P. knowlesi infection had uncomplicated malaria that responded to chloroquine and primaquine treatment. Based on World Health Organization criteria for falciparum malaria, 7 patients with P. knowlesi infection (6.5%) had severe infections at hospital admission. The most frequent complication was respiratory distress, which was present at hospital admission in 4 patients and developed after admission in an additional 3 patients. P. knowlesi parasitemia at hospital admission was an independent determinant of respiratory distress, as were serum creatinine level, serum bilirubin, and platelet count at admission (p < .002 for each). Two patients with knowlesi malaria died, representing a case fatality rate of 1.8% (95% confidence interval, 0.2%-6.6%).

    CONCLUSIONS: Knowlesi malaria causes a wide spectrum of disease. Most cases are uncomplicated and respond promptly to treatment, but approximately 1 in 10 patients develop potentially fatal complications.

    Matched MeSH terms: Middle Aged
  17. Chan CY, Kwan MK, Saw LB
    Eur Spine J, 2010 Jan;19(1):78-84.
    PMID: 19763636 DOI: 10.1007/s00586-009-1157-8
    The objective of this cadaveric study is to determine the safety and outcome of thoracic pedicle screw placement in Asians using the funnel technique. Pedicle screws have superior biomechanical as well as clinical data when compared to other methods of instrumentation. However, misplacement in the thoracic spine can result in major neurological implications. There is great variability of the thoracic pedicle morphometry between the Western and the Asian population. The feasibility of thoracic pedicle screw insertion in Asians has not been fully elucidated yet. A pre-insertion radiograph was performed and surgeons were blinded to the morphometry of the thoracic pedicles. 240 pedicle screws were inserted in ten Asian cadavers from T1 to T12 using the funnel technique. 5.0 mm screws were used from T1 to T6 while 6.0 mm screws were used from T7 to T12. Perforations were detected by direct visualization via a wide laminectomy. The narrowest pedicles are found between T3 and T6. T5 pedicle width is smallest measuring 4.1 +/- 1.3 mm. There were 24 (10.0%) Grade 1 perforations and only 1 (0.4%) Grade 2 perforation. Grade 2 or worse perforation is considered significant perforation which would threaten the neural structures. There were twice as many lateral and inferior perforations compared to medial perforations. 48.0% of the perforations occurred at T1, T2 and T3 pedicles. Pedicle fracture occurred in 10.4% of pedicles. Intra-operatively, the absence of funnel was found in 24.5% of pedicles. In conclusion, thoracic pedicle screws using 5.0 mm at T1-T6 and 6.0 mm at T7-T12 can be inserted safely in Asian cadavers using the funnel technique despite having smaller thoracic pedicle morphometry.
    Matched MeSH terms: Middle Aged
  18. Kim YH, Kim KH, Han CS, Park SH, Yang HC, Lee BY, et al.
    J Cosmet Sci, 2008 Sep-Oct;59(5):419-30.
    PMID: 18841306
    Crinum asiaticum Linne var. japonicum has long been used as a rheumatic remedy, as an anti-pyretic and as an anti-ulcer treatment, and for the alleviation of local pain and fever in Korea and Malaysia. In order to investigate the possibility of Crinum asiaticum Linne var. japonicum extract as a cosmetic ingredient, we measured its anti-inflammatory effect by its inhibition of iNOS (inducible nitric oxide synthase) and the release of PGE2, IL-6, and IL-8. We also measured its anti-allergic effect by its inhibition of beta-hexosamidase release. An HPLC experiment after extraction with 95% EtOH at pH 3.5 showed that Crinum asiaticum Linne var. japonicum was mainly composed of lycorine (up to 1%), a well-known immunosuppressor. The content of lycorine varied, depending on the type of plant tissue analyzed and the extraction method. In an anti-inflammatory assay for inhibition of nitric oxide formation on lipopolysaccharide (LPS)-activated mouse macrophage RAW 264.7 cells, the ethanol extract of Crinum asiaticum showed an inhibitory activity of NO production in a dose-dependent manner (IC50 = 58.5 microg/ml). Additional study by RT-PCR demonstrated that the extract of Crinum asiaticum significantly suppressed the expression of the iNOS gene. Moreover, the extract of Crinum asiaticum did not show any cytotoxicity, but did show a cell proliferation effect against LPS (a 10 approximately 60% increase in cell viability). In an assay to determine inhibition of the H2O2-activated release of PGE2, IL-6, and IL-8 in human normal fibroblast cell lines, the release of PGE2 and IL-6 was almost completely inhibited above concentrations of 0.05% and 1%, respectively. Moreover, the release of IL-8 was completely inhibited over the entire range of concentration (>0.0025%). In order to investigate the skin-sensitizing potentials of the extract of Crinum asiaticum, a human clinical test was performed after repeated epicutaneous 48-h applications under an occlusive patch (RIPT). The repeated and single cutaneous applications of Crinum asiaticum Linne var. japonicum extract under the occlusive patch did not provoke any cumulative irritation and sensitization reactions. The result showed that the extract of Crinum asiaticum Linne var. japonicum has a sufficient anti-inflammatory effect. Therefore, Crinum asiaticum Linne var. japonicum extract may be useful for development as an ingredient in cosmetic products.
    Matched MeSH terms: Middle Aged
  19. Hor SY, Lee SC, Wong CI, Lim YW, Lim RC, Wang LZ, et al.
    Pharmacogenomics J, 2008 Apr;8(2):139-46.
    PMID: 17876342
    Previously studied candidate genes have failed to account for inter-individual variability of docetaxel and doxorubicin disposition and effects. We genotyped the transcriptional regulators of CYP3A and ABCB1 in 101 breast cancer patients from 3 Asian ethnic groups, that is, Chinese, Malays and Indians, in correlation with the pharmacokinetics and pharmacodynamics of docetaxel and doxorubicin. While there was no ethnic difference in docetaxel and doxorubicin pharmacokinetics, ethnic difference in docetaxel- (ANOVA, P=0.001) and doxorubicin-induced (ANOVA, P=0.003) leukocyte suppression was observed, with Chinese and Indians experiencing greater degree of docetaxel-induced myelosuppression than Malays (Bonferroni, P=0.002, P=0.042), and Chinese experiencing greater degree of doxorubicin-induced myelosuppression than Malays and Indians (post hoc Bonferroni, P=0.024 and 0.025). Genotyping revealed both PXR and CAR to be well conserved; only a PXR 5'-untranslated region polymorphism (-24381A>C) and a silent CAR variant (Pro180Pro) were found at allele frequencies of 26 and 53%, respectively. Two non-synonymous variants were identified in HNF4alpha (Met49Val and Thr130Ile) at allele frequencies of 55 and 1%, respectively, with the Met49Val variant associated with slower neutrophil recovery in docetaxel-treated patients (ANOVA, P=0.046). Interactions were observed between HNF4alpha Met49Val and CAR Pro180Pro, with patients who were wild type for both variants experiencing least docetaxel-induced neutropenia (ANOVA, P=0.030). No other significant genotypic associations with pharmacokinetics or pharmacodynamics of either drug were found. The PXR-24381A>C variants were significantly more common in Indians compared to Chinese or Malays (32/18/21%, P=0.035) Inter-individual and inter-ethnic variations of docetaxel and doxorubicin pharmacokinetics or pharmacodynamics exist, but genotypic variability of the transcriptional regulators PAR, CAR and HNF4alpha cannot account for this variability.
    Matched MeSH terms: Middle Aged
  20. Fazlina N, Maha A, Jamal R, Zarina AL, Cheong SK, Hamidah H, et al.
    Hematology, 2007 Feb;12(1):33-7.
    PMID: 17364990
    The expression of the multidrug resistance (MDR) proteins may influence the outcome of treatment in patients with acute leukemia. The aim of this study was to determine the IC50 of cytotoxic drugs (cytosine arabinoside, ara-C and daunorubicin, dnr) using the in vitro 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)2H-tetrazolium, inner salt (MTS) assay method. A total of 82 newly diagnosed acute leukemia cases (43 adult myeloid leukaemia, AML cases and 39 acute lymphoblastic leukaemia, ALL cases) and 16 relapsed cases (8 AML cases and 8 ALL cases) were studied. The MTS assay was performed using two cytotoxic drugs, dnr and ara-C. Cells were incubated with different concentrations of drugs for 4 days and the IC50 was extrapolated from the viability curve. In newly diagnosed cases, we found that childhood ALL samples showed higher IC50 values of dnr (0.040 +/- 2.320) compared to adult AML samples (0.021 +/- 0.158). In contrast, newly diagnosed adult AML samples showed higher IC50 values of ara-C (0.157 +/- 0.529) compared to childhood ALL samples (0.100 +/- 2.350). In relapsed cases, two samples of childhood ALL showed IC50 values of dnr (0.910 +/- 1.760) and ara-C (1.310 +/- 2.390), which was higher compared to childhood AML samples (0.129 +/- 0.214 and 0.210 +/- 0.003, respectively). However, there was no correlation between IC50 values of these drugs tested with clinical outcome. In conclusion, we found that MTS assay is an easy, rapid and non laborious method to study in vitro drug resistance in acute leukaemia cases.
    Matched MeSH terms: Middle Aged
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