Prevalence Trend and Clinical Profile of Leprosy Among the Indigenous Penan Community in Rural Baram, Sarawak, Malaysia: A Retrospective Study.

In Malaysia, despite achieving leprosy-elimination status in 1994, leprosy remains a public health issue among the indigenous Penan community in Sarawak. This study aimed to determine the prevalence trend and clinical profile of leprosy among the Penans in rural Baram, Sarawak, Malaysia. A retrospective records review was conducted on 10-year (2008-2018) time trend of annual prevalence rate and 5-year (2013-2018) Penan leprosy patient clinical profile. Out of the 257 new cases of leprosy reported in Sarawak, 42.8% were Penans, and 72.7% were from Baram. The annual Penan ethnic-specific prevalence rate ranged from 2.08 to 35.5/10 000. Forty-six cases were analyzed for clinical profile: There were more males, active case detection, and multibacillary leprosy. The prevalence trend of leprosy among the Penans in rural Baram exceeded recommended elimination targets. Majority of the cases were detected through active case detection, but cases were detected late. Interventions are needed to improve early diagnosis and detection to achieve elimination of leprosy.

Evaluating the impact of a pre-recorded online video on doctor's knowledge and attitude towards leprosy in Sabah and Labuan - a quasi experimental study.

INTRODUCTION: Global actions have been implemented worldwide to eliminate leprosy. However, under-recognition and stigmatisation continue to be the challenges. In Sabah, the grade two disability rate was 0.15/100,000 population in 2019, implicating a significant delay in diagnosis. This study aimed to assess the knowledge and attitude towards leprosy and the impact of lecture intervention among doctors in Sabah and Labuan, Malaysia. MATERIALS AND METHODS: This study consists of two parts. First, a cross-sectional study on the knowledge of and attitude towards leprosy using an online quesitonnaire was conducted among doctors working in the primary care clinics and hospitals in Sabah and Labuan. Subsequently, the participants were asked to watched an online prerecorded video lecture on leprosy and to answered the same questionnaire. RESULTS: Of the 310 participants, one fifth (20.6%) had good knowledge and 36.5% had positive attitude towards leprosy. Being a specialist (adjusted odds ratio [aOR] 4.55, 95% confidence interval [CI] 2.17-9.57, p < 0.001), managed ≥ 5 leprosy cases (aOR 3.37, 95% CI 1.52-7.47, p = 0.003), and involved in educational activities related to leprosy within last year (aOR 4.7, 95% CI 1.69-13.04, p < 0.001) were the significant predictors of good knowledge. Working in tertiary care was significantly associated with good attitude towards leprosy (OR 2.19, 95% CI 1.22-3.94, p = 0.025). There was a significant improvement in participants' knowledge post-intervention (87.0% participants post-lecture vs 20.6% participants pre-lecture with good knowledge, p < 0.001). CONCLUSION: The proportion of doctors in Sabah and Labuan with good knowledge and attitude towards leprosy was low. Knowledge of leprosy improved significantly postintervention. This highlights the need for educational and training programmes to improve doctors' knowledge of leprosy.

Current status of infectious diseases among migrants and non-citizens in Malaysia.

The mass movement of migrants to Malaysia for employment is one of the factors contributing to the emergence and re-emergence of infectious diseases in this country. Despite mandatory health screening for migrants seeking employment, prevalence records of infectious diseases amongst migrant populations in Malaysia are still within negligible proportions. Therefore, the present review highlights the incidence, mortality and overall status of infectious diseases amongst migrants' populations in Malaysia, which maybe be useful for impeding exacerbation of inequalities among them and improving our national health system thru robust and effective emergency responses in controlling the prevalent diseases found among these populations and maybe, Malaysian citizens too. Peer-reviewed articles from January 2016 to December 2020 were searched through online platform including SCOPUS, PubMed, Science Direct, and Google Scholar. Non-peer-reviewed reports and publications from ministry and government websites including data from related agencies were also scoured from in order to ensure that there are no cases being overlooked, as most published articles did not have migrants as the research subjects. A total of 29 studies had been selected in the final analysis. Migrants in Malaysia were at higher risk for tuberculosis, malaria, lymphatic filariasis, cholera, leprosy and leptospirosis. Lymphatic filariasis was still endemic among this population while thousand cases of TB and cholera had been reported among them due to cramp living conditions and poor sanitation in their settlements respectively. While malaria had gradually decreased and become sporadic, the influx of migrant workers had led to the rising of imported malaria cases. Low cases of leprosy had been recorded in Malaysia but a significant proportion of it was contributed by migrant workers. As for leptospirosis, studies found that there are prominent cases among migrant workers, which particularly highest within workers with lower educational attainment. Infectious diseases are still prevalent among migrants in Malaysia due to various interplay factors including their working sectors, country of origin, immunization status, type of settlement, impoverished living conditions, and language and cultural barriers that impeding access to health facilities.

The genome of Shorea leprosula (Dipterocarpaceae) highlights the ecological relevance of drought in aseasonal tropical rainforests.

Hyperdiverse tropical rainforests, such as the aseasonal forests in Southeast Asia, are supported by high annual rainfall. Its canopy is dominated by the species-rich tree family of Dipterocarpaceae (Asian dipterocarps), which has both ecological (e.g., supports flora and fauna) and economical (e.g., timber production) importance. Recent ecological studies suggested that rare irregular drought events may be an environmental stress and signal for the tropical trees. We assembled the genome of a widespread but near threatened dipterocarp, Shorea leprosula, and analyzed the transcriptome sequences of ten dipterocarp species representing seven genera. Comparative genomic and molecular dating analyses suggested a whole-genome duplication close to the Cretaceous-Paleogene extinction event followed by the diversification of major dipterocarp lineages (i.e. Dipterocarpoideae). Interestingly, the retained duplicated genes were enriched for genes upregulated by no-irrigation treatment. These findings provide molecular support for the relevance of drought for tropical trees despite the lack of an annual dry season.

Investigating the myth of smokeless industry: environmental sustainability in the ASEAN countries and the role of service sector and renewable energy.

Since the development of the service sector and renewable energy reduce fossil-based energy consumption which mitigates CO2 emissions and this nexus provides a better understanding of the environmental sustainability. Considering the substantially increasing contribution of service sector and tremendous potential for renewable energy in ASEAN5 countries, leaning forward from ASEAN's energy and growth nexus, this study examines the impact of service sector contribution and renewable energy on the environmental quality of ASEAN5 using annual data from 1990 to 2018. The results of the fully modified ordinary least squared, dynamic ordinary least squared, and canonical co-integrating regressions depicted that the service sectors of Thailand, the Philippines, and Singapore augment CO2 emissions; however, the service sectors of Malaysia and Indonesia could reduce CO2 emissions. The increasing share of renewable energy can enhance environmental quality, but its magnitude varies in ASEAN5 economies; non-renewable energy, population, and economic development deteriorate the environment. Our results confirm the existence of environmental Kuznets curve in all the ASEAN5; the Gregory-Hansen test confirmed that results are robust. Finally, the Granger causality designated that economic development and non-renewable energy have a significant causal relationship with CO2 emission of ASEAN5 countries. These findings suggest that the ASEAN5 economies need to optimize their economic structure for promoting sustainable development in the long run.Graphical abstract.

Quality of life of leprosy patients in Sabah.

OBJECTIVE: To determine the Dermatology Life Quality Index (DLQI) among the subtypes of leprosy and to examine correlation with deformity and lepra reactions. METHODS: This was a cross-sectional study done at Dermatology Outpatient Clinic, Queen Elizabeth Hospital and two health clinics in Kota Kinabalu between 1st April 2019 and 30th November 2019. A standardised case report form was formulated to collect the demographic data and disease profile of the leprosy patients. The quality of life (QoL) was assessed using Dermatology Life Quality Index (DLQI) questionnaire. RESULTS: A total of 54 patients were included with a male to female ratio of 2.4:1 (38 males and 16 females). The mean DLQI score was 8.31±6.15. The difference between the mean DLQI scores among the leprosy subtypes was not significant. The most affected domain was symptoms and feeling followed by daily activities and leisure. Twenty-one patients (38.9%) had facial deformity and they were found to have significantly higher DLQI score. WHO grade 1 and 2 disability were observed in 37 patients (68.5%) with higher DLQI score compared to those without any disability. More than half of patients with MB leprosy (52.2%) developed lepra reactions but the difference of mean DLQI scores were not significant. CONCLUSIONS: Leprosy-related disabilities may predispose patients to develop psychosocial problems which may have negative impact on QoL. Thus, periodic assessment of QoL should be incorporated into the management of leprosy patients.

A systematic review on Piper longum L.: Bridging traditional knowledge and pharmacological evidence for future translational research.

ETHNOPHARMACOLOGICAL RELEVANCE: Piper longum, commonly referred as 'Pippali', has found its traditional use in India, Malaysia, Singapore and other South Asian countries as an analgesic, carminative, anti-diarrhoeic, immunostimulant, post childbirth to check postpartum hemorrhage and to treat asthma, insomnia, dementia, epilepsy, diabetes, rheumatoid arthritis, asthma, spleen disorder, puerperal fever, leprosy etc. AIM OF THE REVIEW: This review offers essential data focusing on the traditional use, phytochemistry and pharmacological profile of Piper longum thereby identifying research gaps and future opportunities for investigation on this plant. MATERIALS AND METHODS: This systematic survey was accomplished as per the PRISMA guidelines. The information was collected from books, and electronic search (PubMed, Science Direct, Lilca and Scielo) during 1967-2019. RESULTS: Many phytochemicals have been identified till date, including alkaloids as its major secondary metabolites (piperine and piperlongumine), essential oil, flavonoids and steroids. These exhibit a wide range of activities including anti-inflammatory, analgesic, anti-oxidant, anti-microbial, anti-cancer, anti-parkinsonian, anti-stress, nootropic, anti-epileptic, anti-hyperglycemic, hepatoprotective, anti-hyperlipidemic, anti-platelet, anti-angiogenic, immunomodulatory, anti-arthritic, anti-ulcer, anti-asthmatic, anthelmintic action, anti-amebic, anti-fungal, mosquito larvicidal and anti-snake venom. CONCLUSION: Amongst various activities, bioscientific clarification in relation to its ethnopharmacological perspective has been evidenced mainly for anti-amebic, anthelminthic, anti-tumor and anti-diabetic activity. However, despite traditional claims, insufficient scientific validation for the treatment of insomnia, dementia, epilepsy, rheumatoid arthritis, asthma, spleen disorder, puerperal fever and leprosy, necessitate future investigations in this direction. It is also essential and critical to generate toxicological data and pharmacokinetics on human subjects so as to confirm its conceivable bio-active components in the body.

Resistencia a los medicamentos del Mycobacterium Leprae detectados en cultivo de almohadilla plantar de ratón entre 1997 y 2013 en Malasia / No disponible

Antecedentes: Después de tres décadas de implementación de la multiterapia (MDT), consistente en una combinación de rifampicina, dapsona y clofazimina, en Malasia la aparición de resistencia farmacológica del Mycobacterium leprae constituye una preocupación, ya que puede llevar al fracaso del tratamiento y la recidiva de la enfermedad. Objetivos: Determinar el modelo de resistencia farmacológica del M. leprae en Malasia. Métodos: Se analizaron los cultivos en almohadilla plantar de ratón (MFP) de todas las biopsias cutáneas de pacientes con lepra borderline lepromatosa y lepra lepromatosa enviados a la Unidad de la Lepra, Laboratorio Nacional de Salud Publica, Sungai Buloh, Malasia, entre 1997-2013. Resultados: Se realizaron 651 cultivos MFP. La edad media de los pacientes fue de 41 anos (rango: 6-88). La proporción varón/hembra era de 3·8:1. Cuatrocientos cuarenta y cuatro pacientes (69·1%) eran malayos. La proporción de M. leprae positivo en cultivo era del 66·6% (433 of 651). El Índice Bacteriologico (IB) y el Índice Morfológico (IM) promedios para los cultivos positivos fue de 3·7 and 2·8 respectivamente. El IB y el IM de los que no crecieron en la MFP eran significativamente menores que los que presentaban cultivos positivos (P < 0·001). La dapsona presento el mayor índice de resistencia del 55% (238 of 433). Sin embargo, el elevado grado de resistencia a la dapsona (0·01%) fue de 6·24%. Hubo 407 MFP con rifampicina 0·003% y 12 (2·9%) resultaron resistentes a la misma. La clofazimina presento el menor grado de resistencia intermedia (0·001%) que fue del 0·2% (1 of 429). No había diferencias significativas entre el patrón de resistencia y género o nacionalidad de los pacientes. Conclusiones: Mas de la mitad de los cultivos MFP presentaron resistencia de baja intensidad a la dapsona; menos del 3% eran resistentes a la rifampicina y la resistencia a la clofazimina resulto muy baja

Background: After three decades of implementing multidrug therapy (MDT) consisting of rifampicin, dapsone and clofazimine in Malaysia, the drug resistance pattern of Mycobacterium leprae is a growing concern as it may lead to failure of treatment and relapse of disease. Objective: To determine the drug resistance patterns of M. leprae in Malaysia. Methods: Mouse footpad (MFP) culture of all skin biopsy samples from patients with borderline lepromatous and lepromatous leprosy sent to the Leprosy Unit, National Public Health Laboratory, Sungai Buloh, Malaysia between 1997-2013 were retrospectively studied. Results: There were 651 MFP cultures performed. The mean age of patients was 41 years old (range: 6-88). The male: female ratio was 3·8:1. Four hundred and forty four patients (69·1%) were Malaysian. The rate of positive M. leprae culture was 66·6% (433 of 651). The mean Bacteriological Index (BI) and median Morphological Index (MI) for those with positive culture were 3·7 and 2·8 respectively. The mean BI and MI of those which failed to grow in the MFP were significantly lower than those with positive cultures (P < 0·001). Dapsone has the highest resistance rate of 55% (238 of 433). Nevertheless, high degree dapsone resistance (0·01%) was 6·24%. There were 407 MFP tests using rifampicin 0·003% and 12 (2·9%) were resistant to it. Clofazimine has the lowest intermediate degree (0·001%) resistance rate of 0·2% (1 of 429). There were no significant differences between the drug resistance pattern and the gender or the nationality of the patients. Conclusion: More than half of our positive MFP cultures showed low-level resistance to dapsone; less than 3% were resistant to rifampicin, and clofazimine resistance remained very low

The Function of HLA-B*13:01 Involved in the Pathomechanism of Dapsone-Induced Severe Cutaneous Adverse Reactions.

Dapsone-induced hypersensitivity reactions may cause severe cutaneous adverse reactions, such as drug reaction with eosinophilia and systemic symptoms (DRESS). It has been reported that HLA-B*13:01 is strongly associated with dapsone-induced hypersensitivity reactions among leprosy patients. However, the phenotype specificity and detailed immune mechanism of HLA-B*13:01 remain unclear. We investigated the genetic predisposition, HLA-B*13:01 function, and cytotoxic T cells involved in the pathogenesis of dapsone-induced severe cutaneous adverse reactions. We enrolled patients from Taiwan and Malaysia with DRESS and maculopapular eruption with chronic inflammatory dermatoses. Our results showed that the HLA-B*13:01 allele was present in 85.7% (6/7) of patients with dapsone DRESS (odds ratio = 49.64, 95% confidence interval = 5.89-418.13; corrected P = 2.92 × 10-4) but in only 10.8% (73/677) of general population control individuals in Taiwan. The level of granulysin, the severe cutaneous adverse reaction-specific cytotoxic protein released from cytotoxic T cells, was increased in both the plasma of DRESS patients (36.14 ± 9.02 ng/ml, P < 0.05) and in vitro lymphocyte activation test (71.4%, 5/7 patients) compared with healthy control individuals. Furthermore, dapsone-specific cytotoxic T cells were significantly activated when co-cultured with HLA-B*13:01-expressing antigen presenting cells in the presence of dapsone (3.9-fold increase, compared with cells with no HLA-B*13:01 expression; P < 0.01). This study indicates that HLA-B*13:01 is strongly associated with dapsone DRESS and describes a functional role for the HLA-restricted immune mechanism induced by dapsone.

Unravelling proximate cues of mass flowering in the tropical forests of South-East Asia from gene expression analyses.

Elucidating the physiological mechanisms of the irregular yet concerted flowering rhythm of mass flowering tree species in the tropics requires long-term monitoring of flowering phenology, exogenous and endogenous environmental factors, as well as identifying interactions and dependencies among these factors. To investigate the proximate factors for floral initiation of mast seeding trees in the tropics, we monitored the expression dynamics of two key flowering genes, meteorological conditions and endogenous resources over two flowering events of Shorea curtisii and Shorea leprosula in the Malay Peninsula. Comparisons of expression dynamics of genes studied indicated functional conservation of FLOWERING LOCUS T (FT) and LEAFY (LFY) in Shorea. The genes were highly expressed at least 1 month before anthesis for both species. A mathematical model considering the synergistic effect of cool temperature and drought on activation of the flowering gene was successful in predicting the observed gene expression patterns. Requirement of both cool temperature and drought for floral transition suggested by the model implies that flowering phenologies of these species are sensitive to climate change. Our molecular phenology approach in the tropics sheds light on the conserved role of flowering genes in plants inhabiting different climate zones and can be widely applied to dissect the flowering processes in other plant species.

Leprosy--an imported disease.

OBJECTIVES: Leprosy remains a public health concern in Malaysia and globally. We aim to review the characteristics of leprosy patients in a tertiary institution in urban Malaysia. DESIGN: This is a case series of 27 leprosy patients who presented between 2008 and 2013. RESULTS: The majority of our patients consisted of male (74.1%), Malaysian (63.0%), blue collar workers (51.9%) and married (59.3%) patients; 48.1% had lepromatous leprosy. All except one of the patients presented with skin lesions, 25.9% had nerve involvement and 33.3% developed lepra reactions. Forty-four point four percent (44.4%) of the cases seen initially in the primary care setup were misdiagnosed. CONCLUSIONS: Doctors need to have a high index of suspicion for leprosy when patients present with suggestive skin, nerve or musculoskeletal lesions. Immigrants accounted for 37% of cases and these patients may become a reservoir of infection, thus accounting for the rise in incidence. An increasing trend in multibacillary cases may be attributed to the spread from migrants from countries with a high burden of leprosy.

Analysis of the leprosy agents Mycobacterium leprae and Mycobacterium lepromatosis in four countries.

OBJECTIVES: To differentiate the leprosy agents Mycobacterium leprae and Mycobacterium lepromatosis and correlate them with geographic distribution and clinicopathologic features. METHODS: Species-specific polymerase chain reactions were used to detect each bacillus in archived skin biopsy specimens from patients with leprosy from Brazil (n = 52), Malaysia (n = 31), Myanmar (n = 9), and Uganda (n = 4). Findings were correlated with clinical and pathologic data. RESULTS: Etiologic species was detected in 46 of the 52 Brazilian patients, including 36 patients with M leprae, seven with M lepromatosis, and three with both bacilli. The seven patients with sole M lepromatosis all had tuberculoid leprosy, whereas only nine of the 36 patients infected with M leprae exhibited this type, and the rest were lepromatous (P < .001). All patients with dual infections had lepromatous leprosy. Of the nine patients from Myanmar, six were test positive: four with M leprae and two with M lepromatosis. Of the Malaysian and Ugandan patients, only M leprae was detected in 27 of the 31 Malaysians and two of the four Ugandans. CONCLUSIONS: The leprosy agents vary in geographic distribution. Finding M lepromatosis in Brazil and Myanmar suggests wide existence of this newly discovered species. The leprosy manifestations likely vary with the etiologic agents.

Association of leptin/receptor and TNF-α gene variants with adolescent obesity in Malaysia.

BACKGROUND: Leptin (LEP) G-2548A (rs7799039), leptin receptor (LEPR) Q223R (rs1137101) and tumor necrosis factor (TNF)-α G-308A (rs1800629) gene variants have been reported to be associated with obesity, although results for subjects from different countries have been controversial. The aim of this study was to determine the prevalence of overweight and obesity in Malaysian adolescents and the association of these polymorphisms with overweight and obese or over-fat adolescents. METHODS: A total of 613 adolescents (241 Malay, 219 Chinese, 153 Indian) were enrolled. Anthropometric measurements of body mass index (BMI) and body fat percentage were used to classify subjects as controls (non-overweight/obese or normal fat) or as cases (overweight/obese or over-fat). Genomic DNA was extracted from oral buccal mucosa cells for genotyping using polymerase chain reaction-restriction fragment length polymorphism and data obtained were statistically analyzed. RESULTS: A total of 23.3% of subjects were overweight/obese whereas 11.4% were over-fat; there were significantly more overweight/obese and over-fat Indian and Malay adolescents compared to Chinese (P < 0.001). A allele was the minor one for LEPR Q223R and TNF-α G-308A in all ethnic groups, whereas G allele was minor for LEP G-2548A in Chinese and Malay adolescents, except for Indian adolescents. Indian male adolescents with AA genotype for LEP G-2548A were associated with overweight/obesity (P = 0.025; odds ratio, 3.64; 95% confidence interval: 1.15-11.54). Despite the lack of association observed for LEPR Q223R and TNF-α G-308A, Indian and Chinese subjects with AA risk genotype for LEPR Q223R/LEP G-2548A and TNF-α G-308A/LEP G-2548A, respectively, had increased mean BMI (P = 0.049, P = 0.016). CONCLUSIONS: Genotype distribution and association of these polymorphisms with overweight/obesity vary between ethnic groups and genders. Nevertheless, the LEP G-2548A risk allele may be associated with overweight/obese Indian male adolescents in Malaysia.

Multiple rare opportunistic and pathogenic fungi in persistent foot skin infection.

Persistent superficial skin infection caused by multiple fungi is rarely reported. Recently, a number of fungi, both opportunistic and persistent in nature were isolated from the foot skin of a 24-year old male in Malaysia. The fungi were identified as Candida parapsilosis, Rhodotorula mucilaginosa, Phoma spp., Debaryomyces hansenii, Acremonium spp., Aureobasidium pullulans and Aspergillus spp., This is the first report on these opportunistic strains were co-isolated from a healthy individual who suffered from persistent foot skin infection which was diagnosed as athlete's foot for more than 12 years. Among the isolated fungi, C. parapsilosis has been an increasingly common cause of skin infections. R. mucilaginosa and D. hansenii were rarely reported in cases of skin infection. A. pullulans, an emerging fungal pathogen was also being isolated in this case. Interestingly, it was noted that C. parapsilosis, R. mucilaginosa, D. hansenii and A. pullulans are among the common halophiles and this suggests the association of halotolerant fungi in causing persistent superficial skin infection. This discovery will shed light on future research to explore on effective treatment for inhibition of pathogenic halophiles as well as to understand the interaction of multiple fungi in the progress of skin infection.

Nuclear and chloroplast DNA phylogeography reveals Pleistocene divergence and subsequent secondary contact of two genetic lineages of the tropical rainforest tree species Shorea leprosula (Dipterocarpaceae) in South-East Asia.

Tropical rainforests in South-East Asia have been affected by climatic fluctuations during past glacial eras. To examine how the accompanying changes in land areas and temperature have affected the genetic properties of rainforest trees in the region, we investigated the phylogeographic patterns of a widespread dipterocarp species, Shorea leprosula. Two types of DNA markers were used: expressed sequence tag-based simple sequence repeats and chloroplast DNA (cpDNA) sequence variations. Both sets of markers revealed clear genetic differentiation between populations in Borneo and those in the Malay Peninsula and Sumatra (Malay/Sumatra). However, in the south-western part of Borneo, genetic admixture of the lineages was observed in the two marker types. Coalescent simulation based on cpDNA sequence variation suggested that the two lineages arose 0.28-0.09 million years before present and that following their divergence migration from Malay/Sumatra to Borneo strongly exceeded migration in the opposite direction. We conclude that the genetic structure of S. leprosula was largely formed during the middle Pleistocene and was subsequently modified by eastward migration across the subaerially exposed Sunda Shelf.

An epidemiological and clinical analysis of cutaneous adverse drug reactions seen in a tertiary hospital in Johor, Malaysia.

BACKGROUND: The prevalence, clinical patterns, and causative drugs of cutaneous adverse drug reactions (cADR) vary among the different populations previously studied. AIM: To determine the prevalence, the clinical patterns of drug eruptions, and the common drugs implicated, particularly in severe cADR such as Stevens-Johnson Syndrome/Toxic epidermal necrolysis (SJS/TEN) and drug rash with eosinophilia and systemic symptoms (DRESS) in our population. METHODS: We analyzed the database established for all cADR seen by the department of Dermatology from January 2001 till December 2010. RESULTS: A total of 362 cADR were seen among 42 170 new clinic attendees, yielding an incidence rate of 0.86%. The most common reaction pattern seen was maculopapular eruption (153 cases) followed by SJS/TEN (110 cases) and DRESS (34 cases). Antibiotics was the most commonly implicated drug group (146 cases) followed by anticonvulsants (81 cases) and antigout drugs (50 cases). The most frequently implicated drug was allopurinol (50 cases). Carbamazepine, allopurinol, and cotrimoxazole were the three main causative drugs of SJS/TEN accounting for 21.8%, 20.9%, and 12.7%, respectively, of the 110 cases seen, whereas DRESS was mainly caused by allopurinol (15 cases). Mortality rates for TEN, SJS, and DRESS were 28.6%, 2.2%, and 5.9%, respectively. CONCLUSIONS: The low rate of cADR with a high proportion of severe reactions observed in this study was probably due to referral bias. Otherwise, the reaction patterns and drugs causing cADR in our population were similar to those seen in other countries. Carbamazepine, allopurinol, and cotrimoxazole were the three main causative drugs of SJS/TEN in our population.

Patchy stomatal behavior during midday depression of leaf CO2 exchange in tropical trees.

We investigated effects of heterogeneous stomatal behavior on diurnal patterns of leaf gas exchange in 10 tree species. Observations were made in middle and upper canopy layers of potted tropical rainforest trees in a nursery at the Forest Research Institute Malaysia. Measurements were taken from 29 January to 3 February 2010. We measured in situ diurnal changes in net photosynthetic rate and stomatal conductance in three leaves of each species under natural light. In both top-canopy and sub-canopy species, midday depression of net assimilation rate occurred in late morning. Numerical analysis showed that patchy bimodal stomatal behavior occurred only during midday depression, suggesting that the distribution pattern of stomatal apertures (either uniform or non-uniform stomatal behavior) varies flexibly within single days. Direct observation of stomatal aperture using Suzuki's Universal Micro-Printing (SUMP) method demonstrated midday patchy stomatal closure that fits a bimodal pattern in Shorea leprosula Miq., Shorea macrantha Brandis. and Dipterocarpus tempehes V.Sl. Inhibition of net assimilation rate and stomatal conductance appears to be a response to changes in vapor pressure deficit (VPD). Variable stomatal closure with increasing VPD is a mechanism used by a range of species to prevent excess water loss from leaves through evapotranspiration (viz., inhibition of midday leaf gas exchange). Bimodal stomatal closure may occur among adjacent stomata within a single patch, rather than among patches on a single leaf. Our results suggest the occurrence of patches at several scales within single leaves. Further analysis should consider variable spatial scales in heterogeneous stomatal behavior between and within patches and within single leaves.