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  1. Lopez JM, Sivanantham M
    Med J Malaysia, 1998 Sep;53 Suppl A:102-6.
    PMID: 10968191
    This paper summarises our experience of twenty one patients with degenerative arthritis treated by bilateral simultaneous total knee replacement (BSTKR) in Tawakal Hospital in a period of twenty two months vis. January 1994 to November 1995. The results were analysed according to the scoring system of Hospital for Special Surgery. The preliminary observations were encouraging, 90% excellent, 8% good and 2% fair results. The benefits, safety and cost effectiveness of the procedure as compared to the unilateral staged knee replacement are discussed. We recommend that BSTKR be routinely practised for appropriate situations in all institutions where the expertise and facilities are available.
  2. Lopez JB, Balasegaram M, Thambyrajah V
    Int. J. Biol. Markers, 1996 Jul-Sep;11(3):178-82.
    PMID: 8915714
    This study was undertaken to investigate whether serum CA 125 could complement alpha-fetoprotein (AFP) to improve the diagnosis of hepatocellular carcinoma (HCC). CA 125 showed a sensitivity of 92% for HCC against the 58.8% sensitivity of AFP at the cutoff value of 200 ng/ml. However, the former was less specific (48.5% versus 97.4%) in relation to benign liver diseases (BLD). CA 125 had a higher negative predictive value (NPV) of 84.6% compared to 69.2% for AFP; when both markers were combined, however, the NPV rose to 91.7%. Overall, AFP was more efficient than CA 125 for the diagnosis of HCC. While a positive AFP result was highly indicative of HCC, a negative result did not rule out the disease; however, negative AFP and CA 125 meant that the likelihood of the disease was low. In situations of low HCC prevalence, CA 125 could serve as a first-line screening test followed by confirmation of positives by AFP.
  3. Kamariah K, Lopez JB, Satgunasingam N
    Br J Biomed Sci, 1994 Sep;51(3):296-8.
    PMID: 7881328
    We assessed the analytical performance of the Abbott IMxTM immunoassay analyser for total beta human chorionic gonadotropin (Beta hCG), follicle-stimulating hormone (FSH) and luteinising hormone (LH). The within-run CVs for various analyte concentrations were 2% to 6% while those for between-run imprecision in routine assay ranged from 4% to 10%. IMxTM values correlated well with radioimmunoassay for beta hCG, and immunoradiometric assay for FSH and LH; the correlation coefficients (r) were 0.97, 0.99 and 0.98 for total beta hCG, FSH and LH respectively. The average sensitivities were approximately 3.1, 0.2 and 0.5 iu/l for beta hCG, FSH and LH, respectively. Sample carry-over was not detected and there was negligible cross-reaction between LH and beta hCG in the respective assays. The automatic sample dilution protocol for beta hCG was superior to the manual procedure. The IMxTM is easy to operate and is able to process 24 samples in 40-45 minutes.
  4. Lopez JB, Balasegaram M, Thambyrajah V, Timor J
    Malays J Pathol, 1996 Dec;18(2):95-9.
    PMID: 10879229
    This study was undertaken to see if liver function tests (LFT) served a worthwhile purpose in the investigation of hepatocellular carcinoma (HCC). Sera from 80 HCC, 76 benign liver disease (BLD) and 152 healthy adult (HA) subjects were assayed for alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase and lactate dehydrogenase, bilirubin and albumin. Cut-off values were determined from the HA. ALP, GGT, AST and albumin were abnormal in about 90% of the HCC. With the exception of bilirubin, the LFT were abnormal more frequently in HCC than in chronic hepatitis and cirrhosis, the conditions which preceed it. Raised ALP in the presence of normal bilirubin was more often a feature of HCC than BLD although this relationship was not statistically significant. It seems unlikely that LFT serve a useful function in HCC.
  5. Lopez JB, Balasegaram M, Timor J, Thambyrajah V
    Malays J Pathol, 1997 Jun;19(1):53-8.
    PMID: 10879242
    Although alpha-fetoprotein (AFP) is regarded as the reference marker for hepatocellular carcinoma (HCC), it sometimes produces false results. The objective of this study was to see if some of the readily available laboratory markers could complement AFP to improve the laboratory diagnosis of HCC. The markers tested and their sensitivities were: CA 125, 92%; ferritin, 71.3%; CA 19-9, 69.8%; beta-2-microglobulin (B2M), 53.3%; CA 72-4, 13.6%; and carcinoembryonic antigen (CEA), 10.6%. In comparison, AFP had a sensitivity of 58.8%. CA 72-4 and CEA (at the "tumour" cut-off level of 20 ng/ml) had specificities of 100%, and AFP, 97.4%. The specificities of the other markers were less impressive: CEA, 77.8% (at the cut-off level of 5 ng/ml); ferritin, 48.6%; CA 125, 48.5%; B2M, 39.6%; and CA 19-9, 37.3%. The efficiencies of the markers for HCC, which are based on the consideration of sensitivity and specificity together, were as follows: AFP, 77.6%; CA 125, 71.3%; ferritin, 60.5%; CA 19-9, 55.3; B2M, 46.9%; CEA, 40.8%; and CA 72-4, 34.5%. The receiver-operating characteristic plots confirmed AFP to be the most efficient marker for HCC. Nevertheless, it is proposed that CA 125 be combined with AFP for HCC screening because of their excellent sensitivity and specificity, respectively: a negative result for both, or even just CA 125 alone, would indicate that the disease is unlikely while a positive AFP (which would likely occur with a positive CA 125) would make its presence highly probable. A positive CA 125 and negative AFP would be equivocal for HCC. Other markers in combination with AFP are less useful.
  6. Lopez JB, Sahabudin RM, Chin LP
    Int. J. Biol. Markers, 2004 Apr-Jun;19(2):164-7.
    PMID: 15255551
    Increased concentrations of insulin-like growth factor I (IGF-I) and decreased insulin-like growth factor binding protein 3 (IGFBP-3) in serum have been proposed as markers of prostate cancer (CaP). The evidence for this, however, is contradictory. We assayed serum for IGF-I, IGFBP-3 and prostate-specific antigen (PSA) in patients with CaP and benign prostatic hyperplasia (BPH) and in healthy controls (HC). The mean +/- SD concentration of IGF-I in CaP (98.3 +/- 39.3 ng/mL; n = 15) was lower than in BPH (119 +/- 31.1 ng/mL; n=24) and HC (119 +/- 36.1 ng/mL; n=46), but the differences between the three groups were not statistically significant (p > 0.05). The mean IGFBP-3 concentrations in CaP (2691 +/- 1105 ng/mL; n = 16; p = 0.029) and BPH (2618 +/- 816 ng/mL; n = 26; p = 0.006) patients were significantly lower than that of the HC (3119 +/- 618 ng/mL; n=59), but the difference between the two groups of patients was not significant (p > 0.05). PSA concentrations in CaP (median = 80.8 ng/mL; n = 25) were significantly higher than those in BPH (median = 8.6 ng/mL; n = 39) (p < 0.001). Ninety-six percent of CaP and 72% of BPH patients had PSA concentrations >4.0 ng/mL; the proportions of patients with concentrations exceeding 20 ng/mL were 76% and 10%, respectively. We conclude that IGF-I and IGFBP-3 are inferior to PSA for CaP detection.
  7. Lai LC, Lopez J, Kallner A
    PMID: 27454667
  8. Lopez J, Lai LC, Kallner A
    PMID: 27438125
  9. Lopez JB, Thambyrajah V, Balasegaram M, Satgunasingam N
    Br J Biomed Sci, 1994 Jun;51(2):177-80.
    PMID: 7519505
    Sera from 80 Malaysians with confirmed hepatocellular carcinoma were tested for five markers of the hepatitis B virus, anti-HCV and anti-HDV by enzyme immunoassay, and alpha fetoprotein (AFP) was measured by radioimmunoassay. Of the patients, 98.8% had evidence of HBV infection and 75% were positive for HBsAg--which latter correlated with AFP raised above cut-off values of 500 ng/ml (P = 0.0001) and 200 ng/ml (P = 0.005). Males correlated significantly with the presence of HBsAg (P = 0.002). Thirty-one per cent of HBsAg positive patients were also positive for HBeAg and 74% for anti-HBe. Twenty per cent of the cases were concurrently positive for both HBsAg and anti-HBs. Six of 70 (8.6%) patients were positive for anti-HCV, of whom four were also positive for HBsAg. None of 67 patients tested for anti-HDV were positive. The results strongly indicate an important aetiological role for hepatitis B virus in causation of hepatocellular carcinoma among Malaysians.
  10. Singh PN, Kheam T, Lopez J, Job JS, Yel D
    Asia Pac J Public Health, 2013 Sep;25(5 Suppl):54S-63S.
    PMID: 23666842 DOI: 10.1177/1010539513487014
    Although current trends indicate that the rate of cigarette smoking tends to be low among women in the Western Pacific Region (<10%), recent epidemiologic data from South Asia (India, Bangladesh) and Southeast Asia (Cambodia, Vietnam, Indonesia, Malaysia) identify that a large proportion of women of reproductive age and older chew tobacco--often as part of a betel quid mixture that includes other potentially harmful ingredients (eg, areca nut). Our findings from currently pregnant women identified during a nationwide survey of adult tobacco use in Cambodia indicate that 13.0% (95% confidence interval [CI] = 8% to 17%) were current users of smoked or smokeless (in the form of a betel quid) tobacco. Most pregnant women who used tobacco indicated that their habit was either initiated (29.1%; 95% CI = 16.3-46.3) or increased (33.7%; 95% CI = 18.3-53.5) during pregnancy. Pregnancy-related symptoms such as morning sickness were reported as the reason for more than half (54.9%; 95% CI = 34.8-73.4) of the currently pregnant users to have started a tobacco habit during their lifetime. Among those pregnant women who did not use tobacco, we found strong associations (odds ratios from 2 to 14) with beliefs about the harmful effects of tobacco on adult health, faith-based beliefs in addictive substances, and beliefs that influential members of the community, health professionals, and children should not use tobacco. Our findings indicate that tobacco cessation and prevention programs in Cambodia should specifically target pregnant and reproductive-age women.
  11. Berhane Y, Weingartl HM, Lopez J, Neufeld J, Czub S, Embury-Hyatt C, et al.
    Transbound Emerg Dis, 2008 May;55(3-4):165-74.
    PMID: 18405339 DOI: 10.1111/j.1865-1682.2008.01021.x
    Nipah virus (NiV; Paramyxoviridae) caused fatal encephalitis in humans during an outbreak in Malaysia in 1998/1999 after transmission from infected pigs. Our previous study demonstrated that the respiratory, lymphatic and central nervous systems are targets for virus replication in experimentally infected pigs. To continue the studies on pathogenesis of NiV in swine, six piglets were inoculated oronasally with 2.5 x 10(5) PFU per animal. Four pigs developed mild clinical signs, one exudative epidermitis, and one neurologic signs due to suppurative meningoencephalitis, and was euthanized at 11 days post-inoculation (dpi). Neutralizing antibodies reached in surviving animals titers around 1280 at 16 dpi. Nasal and oro-pharyngeal shedding of the NiV was detected between 2 and 17 dpi. Virus appeared to be cleared from the tissues of the infected animals by 23 dpi, with low amount of RNA detected in submandibular and bronchial lymph nodes of three pigs, and olfactory bulb of one animal. Despite the presence of neutralizing antibodies, virus was isolated from serum at 24 dpi, and the viral RNA was still detected in serum at 29 dpi. Our results indicate slower clearance of NiV from some of the infected pigs. Bacteria were detected in the cerebrospinal fluid of five NiV inoculated animals, with isolation of Streptococcus suis and Enterococcus faecalis. Staphylococcus hyicus was isolated from the skin lesions of the animal with exudative epidermitis. Along with the observed lymphoid depletion in the lymph nodes of all NiV-infected animals, and the demonstrated ability of NiV to infect porcine peripheral blood mononuclear cells in vitro, this finding warrants further investigation into a possible NiV-induced immunosuppression of the swine host.
  12. Lopez JB, Royan GP, Lakhwani MN, Mahadaven M, Timor J
    Int. J. Biol. Markers, 1999 Jul-Sep;14(3):172-7.
    PMID: 10569140
    The objective of this study was to compare CA 72-4 with CEA and CA 19-9 in gastrointestinal malignancies. CA 72-4 was assayed by radioimmunoassay and CEA and CA 19-9 with the Abbott IMx analyser. The study included 52 patients with gastrointestinal cancer and 20 controls with benign gastrointestinal diseases. The 52 cases showed marker sensitivities of 39%, 49% and 35% for CA 72-4, CEA and CA 19-9, respectively, and 64% when the markers were combined. Marker expression in serum was highest in colorectal carcinoma followed by gastric and esophageal carcinoma. The sensitivities of the individual markers in colorectal, gastric and esophageal carcinomas, respectively, were: CA 72-4, 56%, 32% and 18%; CEA, 83%, 33% and 18%; CA 19-9, 53%, 25% and 18%. The sensitivity of the three markers in combination was 89%, 50% and 46% in colorectal, gastric and esophageal cancer, respectively. The specificity of CA 72-4, CEA and CA 19-9 was 100%, 72% and 86%, respectively. However, CA 72-4 is not a useful a marker for gastrointestinal cancers because of its poor sensitivity. CEA, which had the best overall sensitivity and a reasonable specificity, was the most useful single marker, especially for colorectal cancer. Whereas the single markers were not useful in gastric and esophageal cancer, the combination of the three may be.
  13. Lai LC, Cheong SK, Goh KL, Leong CF, Loh CS, Lopez JB, et al.
    Malays J Pathol, 2003 Dec;25(2):83-105.
    PMID: 16196365
    Tumour markers are substances related to the presence or progress of a tumour. An ideal tumour marker is (1) detectable only when malignancy is present, (2) specific for the type and site of malignancy, (3) correlates with the amount of malignant tissue present and (4) responds rapidly to a change in tumour size. At present, no tumour marker fulfills all of the above criteria. The first part of the review discusses the clinical usefulness of the commonly requested serum tumour markers, namely, prostate-specific antigen (PSA), CA 19-9, carcinoembryonic antigen (CEA), CA 125, CA 15-3, human chorionic gonadotrophin (hCG) and alpha-foetoprotein (AFP). It is hoped that this review article will decrease the abuse and misuse of these commonly requested serum tumour markers. The second part of the review discusses the clinical usefulness of catecholamines and their metabolites, calcitonin, thyroglobulin, parathyroid hormone, prolactin, adrenocorticotrophic hormone, oestrogen and progesterone receptors, p53, HER-2/c-erbB2, BRCA1 and BRCA2.
  14. Schwalm JR, McCready T, Lamelas P, Musa H, Lopez-Jaramillo P, Yusoff K, et al.
    Am Heart J, 2018 09;203:57-66.
    PMID: 30015069 DOI: 10.1016/j.ahj.2018.06.004
    BACKGROUND: Cardiovascular disease is the leading cause of death throughout the world, with the majority of deaths occurring in low- and middle-income countries. Despite clear evidence for the benefits of blood pressure reduction and availability of safe and low-cost medications, most individuals are either unaware of their condition or not adequately treated.

    OBJECTIVE: The primary objective of this study is to evaluate whether a community-based, multifaceted intervention package primarily provided by nonphysician health workers can improve long-term cardiovascular risk in people with hypertension by addressing identified barriers at the patient, health care provider, and health system levels.

    METHODS/DESIGN: HOPE-4 is a community-based, parallel-group, cluster randomized controlled trial involving 30 communities (1,376 participants) in Colombia and Malaysia. Participants ≥50 years old and with newly diagnosed or poorly controlled hypertension were included. Communities were randomized to usual care or to a multifaceted intervention package that entails (1) detection, treatment, and control of cardiovascular risk factors by nonphysician health workers in the community, who use tablet-based simplified management algorithms, decision support, and counseling programs; (2) free dispensation of combination antihypertensive and cholesterol-lowering medications, supervised by local physicians; and (3) support from a participant-nominated treatment supporter (either a friend or family member). The primary outcome is the change in Framingham Risk Score after 12 months between the intervention and control communities. Secondary outcomes including change in blood pressure, lipid levels, and Interheart Risk Score will be evaluated.

    SIGNIFICANCE: If successful, the study could serve as a model to develop low-cost, effective, and scalable strategies to reduce cardiovascular risk in people with hypertension.

  15. Dooley NL, Chabikwa TG, Pava Z, Loughland JR, Hamelink J, Berry K, et al.
    Nat Commun, 2023 Nov 15;14(1):7387.
    PMID: 37968278 DOI: 10.1038/s41467-023-43181-7
    Plasmodium falciparum malaria drives immunoregulatory responses across multiple cell subsets, which protects from immunopathogenesis, but also hampers the development of effective anti-parasitic immunity. Understanding malaria induced tolerogenic responses in specific cell subsets may inform development of strategies to boost protective immunity during drug treatment and vaccination. Here, we analyse the immune landscape with single cell RNA sequencing during P. falciparum malaria. We identify cell type specific responses in sub-clustered major immune cell types. Malaria is associated with an increase in immunosuppressive monocytes, alongside NK and γδ T cells which up-regulate tolerogenic markers. IL-10-producing Tr1 CD4 T cells and IL-10-producing regulatory B cells are also induced. Type I interferon responses are identified across all cell types, suggesting Type I interferon signalling may be linked to induction of immunoregulatory networks during malaria. These findings provide insights into cell-specific and shared immunoregulatory changes during malaria and provide a data resource for further analysis.
  16. Khan M, Lamelas P, Musa H, Paty J, McCready T, Nieuwlaat R, et al.
    Glob Heart, 2018 Jun;13(2):93-100.e1.
    PMID: 29331282 DOI: 10.1016/j.gheart.2017.11.002
    BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death worldwide. The need to address CVD is greatest in low- and middle-income countries where there is a shortage of trained health workers in CVD detection, prevention, and control.

    OBJECTIVES: Based on the growing evidence that many elements of chronic disease management can be shifted to nonphysician health care workers (NPHW), the HOPE-4 (Heart Outcomes Prevention and Evaluation Program) aimed to develop, test, and implement a training curriculum on CVD prevention and control in Colombia, Malaysia, and low-resource settings in Canada.

    METHODS: Curriculum development followed an iterative and phased approach where evidence-based guidelines, revised blood pressure treatment algorithms, and culturally relevant risk factor counseling were incorporated. Through a pilot-training process with high school students in Canada, the curriculum was further refined. Implementation of the curriculum in Colombia, Malaysia, and Canada occurred through partner organizations as the HOPE-4 team coordinated the program from Hamilton, Ontario, Canada. In addition to content on the burden of disease, cardiovascular system pathophysiology, and CVD risk factors, the curriculum also included evaluations such as module tests, in-class exercises, and observed structured clinical examinations, which were administered by the local partner organizations. These evaluations served as indicators of adequate uptake of curriculum content as well as readiness to work as an NPHW in the field.

    RESULTS: Overall, 51 NPHW successfully completed the training curriculum with an average score of 93.19% on module tests and 84.76% on the observed structured clinical examinations. Since implementation, the curriculum has also been adapted to the World Health Organization's HEARTS Technical Package, which was launched in 2016 to improve management of CVD in primary health care.

    CONCLUSIONS: The robust curriculum development, testing, and implementation process described affirm that NPHW in diverse settings can be trained in implementing measures for CVD prevention and control.

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