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Fulltext ELISA seropositivity for Toxocara canis antibodies in Malaysia, 1989-1991

Hakim SL, Mak JW, Lam PL

Med J Malaysia, 1993 Sep;48(3):303-7.
PMID: 8183143

The laboratory test results for visceral larva migrans (VLM) using ELISA for Toxocara canis antibodies employed by the Institute for Medical Research, Kuala Lumpur, is described. A total of 331 serum samples received from hospitals and general practitioners all over Malaysia were tested. The test utilises excretory-secretory antigens obtained from in vitro culture of second stage T. canis larvae. The overall seropositivity rate was 19.6%, the highest positive rate being in Indians (35.5%), followed by the Malays (14.8%), Chinese (10.9%) and others (29.4%). Seropositivity rate was highest in children below the age of 10; 89% of patients presented with eosinophilia and 93% with VLM syndrome were children.
Fulltext Seroprevalence of Toxocara canis antibodies among Orang Asli (aborigines) in Peninsular Malaysia

Hakim SL, Mak JW, Lam PL, Nazma S, Normaznah Y

Southeast Asian J. Trop. Med. Public Health, 1992 Sep;23(3):493-6.
PMID: 1488706

An enzyme-linked immunosorbent assay using excretory-secretory antigens of the second stage larvae maintained in vitro was used to determine the seroprevalence of Toxocara antibodies in Orang Asli (aborigines) of Peninsular Malaysia. The mean + 3 SD optical density of 30 healthy subjects was used as the cut-off point. Overall prevalence was found to be 31.9%. No significant relationship was found between positive rates with sex and age groups, though children between 0 to 9 years recorded the highest positive rates. Eosinophil counts were found to be closely related to the proportion of positivity to toxocaral infection and mean optical densities. There was some degree of cross-reaction with Trichuris trichuria positive sera.
Effect of ivermectin against subperiodic Brugia malayi infection in the leaf monkey, Presbytis cristata

Mak JW, Lam PL, Rain AN, Suresh K

Parasitol Res, 1988;74(4):383-5.
PMID: 3387410

Ivermectin at single doses of 0.2-1.0 mg/kg body weight reduced the microfilarial counts of subperiodic Brugia malayi in Presbytis cristata by 59.9%-89.6% of initial counts, 4 weeks after treatment. Adult filaricidal activity was poor, live adult worms being recovered from all animals at autopsy. There was no serious side effect at these doses.
Experimental infection of the leaf-monkeys, Presbytis cristata and Presbytis melalophos with subperiodic Brugia malayi

Mak JW, Choong MF, Lam PL, Suresh K

Acta Trop, 1990 May;47(4):223-6.
PMID: 1973024

The leaf-monkeys, Presbytis cristata and Presbytis melalophos, experimentally infected with subperiodic Brugia malayi, have been used for studies on the pathoimmunology of the infection and the screening of potential filaricides during the last 6-8 years, and considerable information on the pattern of microfilaraemia and adult worm recoveries have been obtained. The prepatent periods in 97 P. cristata and 45 P. melalophos, each infected with about 200 infective larvae, were similar, these being approximately 70 and 68 days respectively. Although all infected animals became microfilaraemic, the peak geometric mean count was much higher in P. cristata than in P. melalophos, this being 182.0 and 65.8 per ml blood respectively. Mean adult worm recovery expressed as the percentage of the infective dose was 4.7% and 2.5%, respectively. Most worms were recovered from the sacral nodes/thoracic duct or inguinal lymph nodes in these animals. In view of the higher worm recovery and the higher peak microfilaraemia attained, it is concluded that P. cristata is a better model for the infection than P. melalophos.
Antifilarial activity of CGP 20376 against subperiodic Brugia malayi in the leaf-monkey Presbytis cristata

Mak JW, Suresh K, Lam PL, Choong MF, Striebel HP

Trop. Med. Parasitol., 1990 Mar;41(1):10-2.
PMID: 2339241

CGP 20376, a 5-methoxyl-6-dithiocarbamic-S- (2-carboxy-ethyl) ester derivative of benzothiazole was evaluated for its antifilarial properties and shown to be extremely effective against subperiodic Brugia malayi in the leaf-monkey, Presbytis cristata at oral doses of 20-100 mg/kg. The compound and/or its metabolites had complete micro- and microfilaricidal activities even when given at a single dose of 20 mg/kg. Lower doses had incomplete filaricidal action.
Experimental infection of the leaf-monkey, Presbytis cristata, with subperiodic Brugia malayi

Mak JW, Choong MF, Suresh K, Lam PL

Parasitol Res, 1990;76(8):689-91.
PMID: 2251244

Presbytis cristata monkeys infected through the inoculation of between 200 and 400 subperiodic Brugia malayi infective larvae (L3) in the right thigh, in both thighs or in the dorsum of the right foot were followed up for varying periods of up to about 8 months after infection. All 148 inoculated animals became patent, with mean prepatent periods being between 66 and 76 days. In animals injected in the thigh, the patterns of microfilaraemia were similar, there being a rapid rise in the geometric mean counts (GMCs) of microfilariae during the first 10-12 weeks of patency, which then plateaued at levels of greater than 1000/ml. Adult worm recovery, expressed as the percentage of the infective dose, was significantly higher in animals injected with 100 L3 in each thigh, being 9.4% as compared with 2.8%-4.8% in other groups. It is therefore recommended that animals should be injected with 100 L3 in each thigh and that the testing of potential filaricides in this model be carried out during the phase of rapid increase in microfilaraemia to ensure that any microfilaricidal effect can easily be detected.
Application of phage display for T-cell receptor discovery

Ch'ng ACW, Lam P, Alassiri M, Lim TS

Biotechnol Adv, 2021 Nov 18;54:107870.
PMID: 34801662 DOI: 10.1016/j.biotechadv.2021.107870

The immune system is tasked to keep our body unharmed and healthy. In the immune system, B- and T-lymphocytes are the two main components working together to stop and eliminate invading threats like virus particles, bacteria, fungi and parasite from attacking our healthy cells. The function of antibodies is relatively more direct in target recognition as compared to T-cell receptors (TCR) which recognizes antigenic peptides being presented on the major histocompatibility complex (MHC). Although phage display has been widely applied for antibody presentation, this is the opposite in the case of TCR. The cell surface TCR is a relatively large and complex molecule, making presentation on phage surfaces challenging. Even so, recombinant versions and modifications have been introduced to allow the growing development of TCR in phage display. In addition, the increasing application of TCR for immunotherapy has made it an important binding motif to be developed by phage display. This review will emphasize on the application of phage display for TCR discovery as well as the engineering aspect of TCR for improved characteristics.
Left bundle branch area pacing for heart failure patients requiring cardiac resynchronization therapy: A meta-analysis

Jin C, Dai Q, Li P, Lam P, Cha YM

J Cardiovasc Electrophysiol, 2023 Sep;34(9):1933-1943.
PMID: 37548113 DOI: 10.1111/jce.16013

INTRODUCTION: Left bundle branch area pacing (LBBP) is a novel conduction system pacing method to achieve effective physiological pacing and an alternative to cardiac resynchronization therapy (CRT) with biventricular pacing (BVP) for patients with heart failure with reduced ejection fraction (HFrEF). We conduted this meta-analysis and systemic review to review current data comparing BVP and LBBP in patients with HFrEF and indications for CRT.
METHODS: We searched PubMed/Medline, Web of Science, and Cochrane Library from the inception of the database to November 2022. All studies that compared LBBP with BVP in patients with HFrEF and indications for CRT were included. Two reviewers performed study selection, data abstraction, and risk of bias assessment. We calculated risk ratios (RRs) with the Mantel-Haenszel method and mean difference (MD) with inverse variance using random effect models. We assessed heterogeneity using the I2 index, with I2 > 50% indicating significant heterogeneity.
RESULTS: Ten studies (9 observational studies and 1 randomized controlled trial; 616 patients; 15 centers) published between 2020 and 2022 were included. We observed a shorter fluoroscopy time (MD: 9.68, 95% confidence interval [CI]: 4.49-14.87, I2 = 95%, p p p p p = .04, millimeter). There was a greater improvement in New York Heart Association function class with LBBP (MD: 0.37, 95% CI: 0.05-0.68, I2 = 61%, p = .02). LBBP was also associated with a lower risk of a composite of heart failure hospitalizations (HFH) and all-cause mortality (RR: 0.48, 95% CI: 0.25-0.90, I2 = 0%, p = .02) driven by reduced HFH (RR: 0.39, 95% CI: 0.19-0.82, I2 = 0%, p = .01). However, all-cause mortality rates were low in both groups (1.52% vs. 1.13%) and similar (RR: 0.98, 95% CI: 0.21-4.68, I2 = 0%, p = .87).
CONCLUSION: This meta-analysis of primarily nonrandomized studies suggests that LBBP is associated with a greater improvement in left ventricular systolic function and a lower rate of HFH compared to BVP. There was uniformity of these findings in all of the included studies. However, it would be premature to conclude based solely on the current meta-analysis alone, given the limitations stated. Dedicated, well-designed, randomized controlled trials and observational studies are needed to elucidate better the comparative long-term efficacy and safety of LBBP CRT versus BIV CRT.
Antifilarial activity of intravenous suramin and oral diethylcarbamazine citrate on subperiodic Brugia malayi in the leaf-monkey, Presbytis cristata

Mak JW, Lam PL, Choong MF, Suresh K

J Helminthol, 1990 Jun;64(2):96-9.
PMID: 2387979

The known filaricides, suramin and diethylcarbamazine citrate, were tested against subperiodic Brugia malayi infection in the leaf-monkey, Presbytis cristata. As expected, intravenous suramin at 10 mg/kg daily x 5 days or 17 mg/kg weekly x 5 weeks, did not show any microfilaricidal activity, but substantially reduced the recovery of live adult worms to 50.6% and 13.6% of controls respectively. Oral diethylcarbamazine citrate at 6 mg/kg daily x 6 or 10 days reduced final microfilarial counts to 30% of initial counts four weeks post-treatment and adult worm recovery was reduced to 4.5% and 0% of controls respectively. Although the antifilarial activity of these drugs against the infection in this non-human primate model appears to be similar to that seen in man, these results have to be confirmed using larger groups of animals.
Chemoprophylactic studies with ivermectin against subperiodic Brugia malayi infection in the leaf monkey, Presbytis cristata

Mak JW, Lam PL, Rain AN, Suresh K

J Helminthol, 1987 Dec;61(4):311-4.
PMID: 3437112

Four Presbytis cristata were treated with oral ivermectin at the same time as the subcutaneous inoculation of 100 infective larvae monthly for three months. Two animals given 0.2 mg/kg monthly and two others given 0.3 mg/kg monthly as well as three control animals became patent for microfilaraemia. However, only 1% of the infective dose was recovered as adult worms from animals in the higher drug dosage group compared to 8.2% and 6.2% in the lower dosage and control groups respectively.
Fulltext Pharmacokinetics and Acceptability of Subcutaneous Injection of Testosterone Undecanoate

Turner L, Ly LP, Desai R, Singh GKS, Handelsman TD, Savkovic S, et al.

J Endocr Soc, 2019 Aug 01;3(8):1531-1540.
PMID: 31384715 DOI: 10.1210/js.2019-00134

Context: Can injectable testosterone undecanoate (TU) be administered effectively and acceptably by the subcutaneous (SC) route?
Objective: To investigate the acceptability and pharmacokinetics (PK) of SC injection of TU.
Design: Randomized sequence, crossover clinical study of SC vs IM TU injections.
Setting: Ambulatory clinic of an academic andrology center.
Participants: Twenty men (11 hypogonadal, 9 transgender men) who were long-term users of TU. injections. Intervention: Injection of 1000 mg TU (in 4 mL castor oil vehicle) by SC or IM route. Main Outcome Measures: Patient-reported pain, acceptability, and preference scales. PK by measurement of serum testosterone, dihydrotestosterone (DHT), and estradiol (E2) concentrations with application of population PK methods and dried blood spot (DBS) sampling.
Results: Pain was greater after SC compared with IM injection 24 hours (but not immediately) after injection but both routes were equally acceptable. Ultimately 11 preferred IM, 6 preferred SC, and 3 had no preference. The DBS-based PK analysis of serum testosterone revealed a later time of peak testosterone concentration after SC vs IM injection (8.0 vs 3.3 days) but no significant route differences in model-predicted peak testosterone concentration (8.4 vs 9.6 ng/mL) or mean resident time (183 vs 110 days). The PK of venous serum testosterone, DHT, and E2 did not differ according to route of injection.
Conclusions: We conclude that SC TU injection is acceptable but produces greater pain 24 hours after injection that may contribute to the overall majority preference for the IM injection. The PK of testosterone, DHT, or E2 did not differ substantially between SC and IM routes. Hence whereas further studies are required, the SC route represents an alternative to IM injections without a need to change dose for men for whom IM injection is not desired or recommended.
Diffusion-in-gel enzyme-linked immunosorbent assay, ELISA and IFA test in the detection of malarial antibodies

Kumar GS, Mak JW, Lam PL, Tan MA, Lim PK

Southeast Asian J. Trop. Med. Public Health, 1987 Dec;18(4):502-6.
PMID: 3129797

Malarial antibodies in 80 patients were measured using the diffusion-in-gel enzyme linked immunosorbent assay (DIG-ELISA), enzyme-linked immunosorbent assay (ELISA) and the indirect fluorescent antibody (IFA) test. Good correlations were obtained between all three tests in terms of sensitivity and reliability. DIG-ELISA has the advantage of being a rapid diagnostic tool for the detection of malarial antibodies.
Self-perceived disease control in childhood eczema

Lam PH, Hon KL, Leung K, Leong KF, Li CK, Leung TF

J Dermatolog Treat, 2020 Sep 22.
PMID: 32962454 DOI: 10.1080/09546634.2020.1826395

BACKGROUND: Atopic eczema (AE) is a common relapsing inflammatory skin disease in children which is often associated with chronicity and poor quality of life. Unlike atopic asthma, control of AE is seldom assessed in therapeutics.
AIM: To investigate the utility of a Traffic Light Control (TLC) system as a measurement/assessment of self-perceived eczema control.
METHODS: This is a prospectively study of all Chinese children (aged 6 to 18 years old) with eczema attending the paediatric dermatology clinic of a tertiary hospital from Jan to June 2020. Eczema control, eczema severity, quality of life and biophysical skin condition of consecutive patients at the paediatric dermatology clinic of a teaching hospital were evaluated with the validated Chinese versions of Depressive, Anxiety, Stress Scales (DASS-21), Patient Oriented Eczema Measure (POEM), transepidermal water loss (TEWL), and stratum corneum skin hydration (SH), respectively. With a visual TLC analogy, patients were asked if their eczema is under control (green light), worsening (yellow) or in flare-up (red light).
RESULTS: Among AE patients (n = 36), self-perceived TLC as green (under control), amber (worsening) and red (flare up) reflected acute and chronic severity (SCORAD, NESS, POEM) and quality of life (CDLQI) (p< 0.0001), but not SH, TEWL or Depression, anxiety and stress.
CONCLUSIONS: Eczema control can be semi-quantified with a child-friendly TLC self-assessment system. AE patients reporting worse eczema control have worse acute and chronic eczema severity, more impairment of quality of life; but not the psychologic symptoms of depression, anxiety and stress or skin hydration or transepidermal water loss. TLC can be linked to an eczema action plan to guide patient management.
Fulltext Prevalence of simian malaria parasites in macaques of Singapore

Li MI, Mailepessov D, Vythilingam I, Lee V, Lam P, Ng LC, et al.

PLoS Negl Trop Dis, 2021 Jan;15(1):e0009110.
PMID: 33493205 DOI: 10.1371/journal.pntd.0009110

Plasmodium knowlesi is a simian malaria parasite currently recognized as the fifth causative agent of human malaria. Recently, naturally acquired P. cynomolgi infection in humans was also detected in Southeast Asia. The main reservoir of both parasites is the long-tailed and pig-tailed macaques, which are indigenous in this region. Due to increased urbanization and changes in land use, there has been greater proximity and interaction between the long-tailed macaques and the general population in Singapore. As such, this study aims to determine the prevalence of simian malaria parasites in local macaques to assess the risk of zoonosis to the general human population. Screening for the presence of malaria parasites was conducted on blood samples from 660 peridomestic macaques collected between Jan 2008 and Mar 2017, and 379 wild macaques collected between Mar 2009 and Mar 2017, using a Pan-Plasmodium-genus specific PCR. Positive samples were then screened using a simian Plasmodium species-specific nested PCR assay to identify the species of parasites (P. knowlesi, P. coatneyi, P. fieldi, P. cynomolgi, and P. inui) present. All the peridomestic macaques sampled were tested negative for malaria, while 80.5% of the 379 wild macaques were infected. All five simian Plasmodium species were detected; P. cynomolgi being the most prevalent (71.5%), followed by P. knowlesi (47.5%), P. inui (42.0%), P. fieldi (32.5%), and P. coatneyi (28.5%). Co-infection with multiple species of Plasmodium parasites was also observed. The study revealed that Singapore's wild long-tailed macaques are natural hosts of the five simian malaria parasite species, while no malaria was detected in all peridomestic macaques tested. Therefore, the risk of simian malaria transmission to the general human population is concluded to be low. However, this can be better demonstrated with the incrimination of the vectors of simian malaria parasites in Singapore.

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