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Fulltext Influence of Cytochrome P450, Family 2, Subfamily D, Polypeptide 6 (CYP2D6) polymorphisms on pain sensitivity and clinical response to weak opioid analgesics

Zahari Z, Ismail R

Drug Metab. Pharmacokinet., 2014;29(1):29-43.
PMID: 23759977

CYP2D6 polymorphisms show large geographical and interethnic differences. Variations in CYP2D6 activity may impact upon a patient's pain level and may contribute to interindividual variations in the response to opioids. This paper reviews the evidence on how CYP2D6 polymorphisms might influence pain sensitivity and clinical response to codeine and tramadol. For example, it is shown that (1) CYP2D6 poor metabolizers (PMs) may be less efficient at synthesizing endogenous morphine compared with other metabolizers. In contrast, ultra-rapid metabolizers (UMs) may be more efficient than other metabolizers at synthesizing endogenous morphine, thus strengthening endogenous pain modulation. Additionally, for codeine and tramadol that are bioactivated by CYP2D6, PMs may undergo no metabolite formation, leading to inadequate analgesia. Conversely, UMs may experience quicker analgesic effects but be prone to higher mu-opioid-related toxicity. The literature suggested the potential usefulness of the determination of CYP2D6 polymorphisms in elucidating serious adverse events and in preventing subsequent inappropriate selection or doses of codeine and tramadol. Notably, even though many studies investigated a possible role of the CYP2D6 polymorphisms on pain sensitivity, pharmacokinetics and pharmacodynamics of these drugs, the results of analgesia and adverse effects are conflicting. More studies are required to demonstrate genetically determined unresponsiveness and risk of developing serious adverse events for patients with pain and these should involve larger numbers of patients in different population types.
Neonatal tumours in Malaysia: a call for heightened awareness

Yeap BH, Zahari Z

Pediatr Surg Int, 2010 Feb;26(2):207-12.
PMID: 19943053 DOI: 10.1007/s00383-009-2523-7

Neonatal neoplasms are rare tumours notorious for their atypical presentation and unpredictable behaviour. Their optimal treatment remains uncertain, a dilemma compounded by the deleterious effects of adjuvant chemo- or radiotherapy during this vulnerable period of growth. This paper examined the relatively high incidence of these tumours and its impact on paediatric surgery in Malaysia.
Gross anatomy and ultrasonographic images of the reproductive system of the Malayan tapir (Tapirus indicus)

Lilia K, Rosnina Y, Abd Wahid H, Zahari ZZ, Abraham M

Anat Histol Embryol, 2010 Dec;39(6):569-75.
PMID: 20809915 DOI: 10.1111/j.1439-0264.2010.01030.x

The Malayan tapir (Tapirus indicus) is the largest among the four tapir species and is listed as an endangered species. Ultrasound examination and description of the external anatomy of the female reproductive system of three adult females were performed, whereas the internal anatomy was investigated in necropsied samples of four adult females and one subadult female. Descriptions of the male external genitalia were conducted on one adult male. Gross examination revealed the presence of a bicornuate uterus. The uterine cervix is firm and muscular with projections towards its lumen, which is also evident on ultrasonography. The elongated and relatively small ovaries, which have a smooth surface, could not be imaged on ultrasonography, due to their anatomical position. The testes are located inside a slightly pendulous scrotum that is sparsely covered with soft, short hairs. The penis has one dorsal and two lateral penile projections just proximal to the glans penis.
Fulltext Effectiveness of Strengthening Exercises for the Elderly with Low Back Pain to Improve Symptoms and Functions: A Systematic Review

Ishak NA, Zahari Z, Justine M

Scientifica (Cairo), 2016;2016:3230427.
PMID: 27293970 DOI: 10.1155/2016/3230427

Objective. To determine the effect of strengthening exercises for older people with low back pain (LBP). Methods. This study is a systematic review of experimental study which evaluated the evidence regarding exercises for older people with LBP by using EBSCO Academic Search Premier, EBSCO EconLit, Science Direct, PUBMED, and PEDro from 2006 to 2016. Search strategy for each database was conducted by using keywords such as "low back pain", "older people", and "strengthening exercise". Boolean operators were used to combine keywords and manual exclusion was conducted to verify studies which met the inclusion criteria. The articles reviewed were evaluated and critically appraised by using PEDro scale and SPSS version 20 was used to analyze the data. Results. Three articles were found regarding strengthening exercise for older people with LBP whereas one study was conducted on multicomponent exercise. The mean, standard deviation, and variance of the PEDro score of all the studies were 5.67, 2.33, and 1.528, respectively. Overall, the qualities of all studies reviewed were fair. Two articles showed significant results when compared to control group (p < 0.05). Conclusions. Strengthening exercise is a beneficial treatment for older people with LBP in reducing pain intensity, disability, and improved functional performances.
Gross anatomy and ultrasonographic images of the reproductive system of the Sumatran rhinoceros (Dicerorhinus sumatrensis)

Zahari ZZ, Rosnina Y, Wahid H, Jainudeen MR

Anat Histol Embryol, 2002 Dec;31(6):350-4.
PMID: 12693754

The Sumatran rhinoceros (Dicerorhinus sumatrensis) is the smallest of all the rhino species. It is one of the rarest mammals in the world and is in imminent danger of extinction. A study was carried out on seven wild-caught females, three wild-caught males and one captive born female Sumatran rhinoceros at the Sumatran Rhinoceros Breeding Centre in Sungai Dusun, Selangor, Malaysia, beginning 1990. As a result of the paucity of scientific information on the reproductive biology of the Sumatran rhinoceros, this study was conducted to obtain information, which could assist in the captive breeding of this endangered and near extinct species. The anatomy of the reproductive system was based on two post-mortem specimens and transrectal real-time ultrasonography in six adult females. Genitalia of the Sumatran rhinoceros were similar to those of other species of rhinoceroses. The cervix consisted of several folds, the uterus was bicornuate with a short body and prominent horns and the ovaries were completely covered by the fimbriated end of the fallopian tube. The internal genitalia could be imaged by ultrasonography. The testes were located within a pendulous scrotum. Two lateral projections were located at the base of the penis. A well-defined process glandis was present at the tip of the penis. The accessory sex glands and the testes could be imaged by ultrasonography.
Immunohistochemical expressions of p75, s100, PGP 9.5 and c-KIT in resected bowel of hirchsprung's disease and correlation with postoperative complication

Omar E, Adhwan F, Talib A, Zahari Z

Pathology, 2016 Feb;48 Suppl 1:S147.
PMID: 27772921 DOI: 10.1016/j.pathol.2015.12.401
Fulltext Kinesiophobia, Pain, Muscle Functions, and Functional Performances among Older Persons with Low Back Pain

Ishak NA, Zahari Z, Justine M

Pain Res Treat, 2017;2017:3489617.
PMID: 28634547 DOI: 10.1155/2017/3489617

OBJECTIVES: This study aims (1) to determine the association between kinesiophobia and pain, muscle functions, and functional performances and (2) to determine whether kinesiophobia predicts pain, muscle functions, and functional performance among older persons with low back pain (LBP).
METHODS: This is a correlational study, involving 63 institutionalized older persons (age = 70.98 ± 7.90 years) diagnosed with LBP. Anthropometric characteristics (BMI) and functional performances (lower limb function, balance and mobility, and hand grip strength) were measured. Muscle strength (abdominal and back muscle strength) was assessed using the Baseline® Mechanical Push/Pull Dynamometer, while muscle control (transverse abdominus and multifidus) was measured by using the Pressure Biofeedback Unit. The pain intensity and the level of kinesiophobia were measured using Numerical Rating Scale and Tampa Scale of Kinesiophobia, respectively. Data were analyzed using Pearson's correlation coefficients and multivariate linear regressions.
RESULTS: No significant correlations were found between kinesiophobia and pain and muscle functions (all p > 0.05). Kinesiophobia was significantly correlated with mobility and balance (p = 0.038, r = 0.263). Regressions analysis showed that kinesiophobia was a significant predictor of mobility and balance (p = 0.038).
CONCLUSION: We can conclude that kinesiophobia predicted mobility and balance in older persons with LBP. Kinesiophobia should be continuously assessed in clinical settings to recognize the obstacles that may affect patient's compliance towards a rehabilitation program in older persons with LBP.
Muscle Functions and Functional Performance among Older Persons with and without Low Back Pain

Ishak NA, Zahari Z, Justine M

Curr Gerontol Geriatr Res, 2016;2016:8583963.
PMID: 27872641

This study aims to compare muscle functions and functional performances between older persons with and without low back pain (LBP) and to determine the association between muscle functions and functional performances. This is a cross-sectional study, involving 95 older persons (age = 70.27 ± 7.26 years). Anthropometric characteristics, muscle functions, and functional performances were measured. Data were analyzed using ANOVA, Pearson's correlation, and multiple linear regression. The functional performances showed no significant differences (females LBP versus non-LBP, males LBP versus non-LBP) (p < 0.05). For muscle functions, significant differences were found (females LBP versus non-LBP) for abdominal muscle strength (p = 0.006) and back muscle strength (p = 0.07). In the LBP group, significant correlations were found between back and abdominal muscle strength and hand grip strength (r = 0.377 and r = 0.396, resp.), multifidus control and lower limb function (r = 0.363) in females, and back muscle strength and lower limb function (r = 0.393) in males (all p < 0.05). Regression analysis showed that abdominal and back muscle strengths were significant predictors of hand grip strength (p = 0.041 and p = 0.049, resp.), and multifidus control was a significant predictor of lower limb function in females (p = 0.047). This study demonstrates that older women with LBP exhibit poorer muscle functions compared to older women without LBP.
The effectiveness of patient education in improving pain, disability and quality of life among older people with low back pain: A systematic review

Zahari Z, Ishak A, Justine M

J Back Musculoskelet Rehabil, 2020;33(2):245-254.
PMID: 31356191 DOI: 10.3233/BMR-181305

OBJECTIVES: This study aimed to gain an overview of patient education and the effects of patient education for older people with low back pain (LBP).
METHODS: The search strategies were performed via EBSCO MEDLINE, EBSCO CINAHL, Science Direct, PubMed, and PEDro databases from 2006 to 2016. The keywords "patient education", "low back pain", "elderly", "older adults", "older persons" and "older people" were used during the literature search. Boolean operators were used to expand or limit the searching scope and manual exclusion was performed to choose articles eligible for this study.
RESULTS: A total of 2799 articles were retrieved but only five articles were related with patient education for older people with LBP. Findings suggest that patient education for older people may differ in terms of its contents such as health education, self-management, video education, and postural education. The high methodological quality of the studies revealed that patient education showed improvement in terms of pain, disability and quality of life among older people with LBP.
CONCLUSIONS: Patient education improved pain and had positive effects on disability and quality of life among older people with LBP. However, due to the limited number of RCTs more studies are needed to provide evidence for its effectiveness.
Influence of DRD2 polymorphisms on the clinical outcomes of patients with schizophrenia

Zahari Z, Teh LK, Ismail R, Razali SM

Psychiatr Genet, 2011 Aug;21(4):183-9.
PMID: 21206399 DOI: 10.1097/YPG.0b013e3283437250

Variations in the gene for dopamine D2 receptor (DRD2) might have an influence on the outcome of antipsychotic treatment in schizophrenia. The objective of this study was to investigate the influence of DRD2 polymorphisms on treatment outcomes in patients with schizophrenia.
Reproductive behaviour of captive Sumatran rhinoceros (Dicerorhinus sumatrensis)

Zainal Zahari Z, Rosnina Y, Wahid H, Yap KC, Jainudeen MR

Anim. Reprod. Sci., 2005 Feb;85(3-4):327-35.
PMID: 15581515

The Sumatran rhinoceros (Dicerorhinus sumatrensis) is on the verge of extinction in Malaysia. At the Sumatran rhinoceros Conservation Centre in Sungai Dusun, the reproductive behaviour of two female and two male rhinoceroses were studied for 8-10 months during attempts to breed them in captivity. Due to the paucity of scientific information on the reproductive biology of the Sumatran rhinoceros, this study was conducted to obtain information on the reproductive behaviour of this species. The male rhino was introduced to a female rhino in the morning for 1-2 h daily in order to observe for behavioural oestrus. Observations were made on the signs of oestrus and mating behaviour. Oestrus was determined by receptivity towards the male and lasted about 24 h. Common signs of oestrus were an increase in frequency of urine spraying, tail raising or swinging, anogenital and other contacts. Although the males exhibited mounting, the inability of the male to achieve intromission was poor. The study demonstrated that the pattern of courtship and copulation of the captive Sumatran rhinos were comparable with those of other rhino species, reported previously by other scientists and flehmen reflex was also exhibited by the male Sumatran rhinos. In a captive breeding programme, it is recommended that only an oestral female is introduced into a male enclosure due to the male solitary behaviour and to avoid serious injuries inflicted onto the females.
Development of resazurin-based assay in 384-well format for high throughput whole cell screening of Trypanosoma brucei rhodesiense strain STIB 900 for the identification of potential anti-trypanosomal agents

Lim KT, Zahari Z, Amanah A, Zainuddin Z, Adenan MI

Exp Parasitol, 2016 Mar;162:49-56.
PMID: 26772786 DOI: 10.1016/j.exppara.2016.01.002

To accelerate the discovery of novel leads for the treatment of Human African Trypanosomiasis (HAT), it is necessary to have a simple, robust and cost-effective assay to identify positive hits by high throughput whole cell screening. Most of the fluorescence assay was made in black plate however in this study the HTS assay developed in 384-well format using clear plate and black plate, for comparison. The HTS assay developed is simple, sensitive, reliable and reproducible in both types of plates. Assay robustness and reproducibility were determined under the optimized conditions in 384-well plate was well tolerated in the HTS assay, including percentage of coefficient of variation (% CV) of 4.68% and 4.74% in clear and black 384-well plate, signal-to-background ratio (S/B) of 12.75 in clear 384-well plate and 12.07 in black 384-well plate, Z' factor of 0.79 and 0.82 in clear 384-well plate and black 384-well plate, respectively and final concentration of 0.30% dimethylsulfoxide (DMSO) in both types of plate. Drug sensitivity was found to be comparable to the reported anti-trypanosomal assay in 96-well format. The reproducibility and sensitivity of this assay make it compliant to automated liquid handler use in HTS applications.
Fine needle aspiration cytology of undifferentiated embryonal sarcoma of the liver: a case report

Sharifah NA, Muhaizan WM, Rahman J, Zulfikar A, Zahari Z

Malays J Pathol, 1999 Dec;21(2):105-9.
PMID: 11068415

The cytological features of a rare case of undifferentiated (embryonal) sarcoma of the liver are presented. The cytology smears showed singly dispersed polygonal and spindle cells as well as loose clusters of cells held together in myxoid material. Neoplastic cells were generally large with round, oval or lobulated nuclei. The cytoplasm was variable in amount with ill-defined borders. Occasional multinucleated cells were also present. Hyaline globules were present on sections of the cell block. Immunohistochemical studies performed showed positivity for vimentin, cytokeratin and alpha-1-antitrypsin (AAT) in the tumour cells.
An analysis of genetic association in opioid dependence susceptibility

Nagaya D, Zahari Z, Saleem M, Yahaya BH, Tan SC, Yusoff NM

J Clin Pharm Ther, 2018 Feb;43(1):80-86.
PMID: 28656735 DOI: 10.1111/jcpt.12585

WHAT IS KNOWN: Drug addiction is a novelty-seeking personality trait that is associated with the candidate genes OPRD1 (opioid delta receptors), OPRK1 (opioid kappa receptors) and PDYN (prodynorphin). However, associations between single nucleotide polymorphisms (SNPs) rs1042114 (80G>T) of the OPRD1 gene, rs702764 (843 A>G) of the OPRK1 gene, and rs910080 (3' UTR _743T>C), rs1997794 (5' UTR -381A>G) and rs1022563 (3' UTR) of the PDYN gene and novelty seeking remain controversial as reported results have not been reproducible.
OBJECTIVE: The goal of this study was to determine the frequencies of SNPs rs1042114, rs702764, rs1997794, rs1022563 and rs910080 in the Malaysian population and to study their association with opioid dependence in Malaysian Malays.
METHODS: A total of 459 Malay male with opioid dependence and 543 healthy male (controls) subjects were included in this study. SNPs were genotyped using the TaqMan SNP genotyping assay. Statistical analysis was performed using Golden Helix SVS software suite to identify the distribution of allele and genotype frequencies, and SNP-SNP interactions were also analysed in this study.
RESULTS AND DISCUSSION: SNP rs1042114 in the OPRD1 gene is strongly associated with opiate addiction (P=.0001). In individuals homozygous for this risk allele, the likelihood of opiate addiction is increased by a factor 1.62 (95% confidence interval (CI) 1.412-1.875). Polymorphic alleles at SNP rs702764 of OPRK1 were not associated with opioid dependence. A significant association between opioid dependence and SNP rs910080 of PDYN (P=.0217) was detected, but there was no association for SNPs rs199774 and rs1022563. A significant interaction was also identified between homozygous wild-type genotype TT of rs702764 with the risk genotypes TG/GG of rs1042114 (odds ratio (OR)=2.111 (95% CI 1.227-3.631), P=.0069) and with the risk genotypes GA/AA of rs910080 (OR=1.415 (95% CI 1.04-1.912), P=.0239).
WHAT IS NEW AND CONCLUSION: The results indicate that SNPs rs1042114 and rs910080 contribute to vulnerability to opioid dependence in the Malaysian Malay population. These results will help us to understand the effect of the SNPs and the SNP-SNP interaction on opioid dependence and may assist in efforts to screen vulnerable individuals and match them with individually tailored prevention and treatment strategies.
Sleep quality in opioid-naive and opioid-dependent patientson methadone maintenance therapy in Malaysia

Zahari Z, Inrahim MA, Tan SC, Mohamad N, Ismail R

Turk J Med Sci, 2016 Dec 20;46(6):1743-1748.
PMID: 28081321 DOI: 10.3906/sag-1507-132

BACKGROUND/AIM: Sleep disturbances may contribute to poor treatment outcomes in opioid-dependent patients. The extent to which the sleep profiles of opioid-dependent patients differ from those of the general Malaysian population is not documented. This study compared opioid-naive subjects and opioid-dependent patients on methadone maintenance therapy (MMT) in terms of their sleep quality.
MATERIALS AND METHODS: Participants comprised Malay male opioid-naive subjects (n = 159) and opioid-dependent patients (n = 160) from MMT clinics in Kelantan, Malaysia, between March and October 2013. Sleep quality was evaluated using the translated and validated Malay version of the Pittsburgh Sleep Quality Index (PSQI).
RESULTS: The opioid-dependent patients exhibited higher global PSQI scores [adjusted mean (95% CI) = 5.46 (5.02, 5.90)] than the opioid-naive group [4.71 (4.26, 5.15)] [F (1, 313) = 4.77, P = 0.030].
CONCLUSION: This study confirmed the poorer sleep quality among opioid-dependent patients on MMT, as manifested by their higher global PSQI scores. The sleep complaints in this patient population are a factor to consider and, when necessary, sleep evaluation and treatment should be undertaken to improve MMT patients' quality of sleep and overall treatment outcome.
Fulltext A Case of Persistent Urogenital Sinus: Pitfalls and challenges in diagnosis

Tan HH, Tan SK, Shunmugan R, Zakaria R, Zahari Z

Sultan Qaboos Univ Med J, 2017 Nov;17(4):e455-e459.
PMID: 29372089 DOI: 10.18295/squmj.2017.17.04.013

Persistent urogenital sinus (PUGS) is a rare anomaly whereby the urinary and genital tracts fail to separate during embryonic development. We report a three-year-old female child who was referred to the Sabah Women & Children Hospital, Sabah, Malaysia, in 2016 with a pelvic mass. She had been born prematurely at 36 gestational weeks via spontaneous vaginal delivery in 2013 and initially misdiagnosed with neurogenic bladder dysfunction. The external genitalia appeared normal and an initial sonogram and repeat micturating cystourethrograms did not indicate any urogenital anomalies. She therefore underwent clean intermittent catheterisation. Three years later, the diagnosis was corrected following the investigation of a persistent cystic mass posterior to the bladder. At this time, a clinical examination of the perineum showed a single opening into the introitus. Magnetic resonance imaging of the pelvis revealed gross hydrocolpos and a genitogram confirmed a diagnosis of PUGS, for which the patient underwent surgical separation of the urinary and genital tracts.
Fulltext Influence of CYP2D6 polymorphisms on symptomatology and side-effects of patients with schizophrenia in Malaysia

Zahari Z, Salleh MR, Teh LK, Ismail R

Malays J Med Sci, 2009 Jul;16(3):12-20.
PMID: 22589660 MyJurnal

Our objective was to investigate the association of CYP2D6 polymorphisms with symptoms and side-effects of patients with schizophrenia.
A cross sectional study on assessing the knowledge, attitude and perception towards allergic reactions of paracetamol in Malaysia

Dellemin NA, Zahari Z, Ahmad Hassali MA, Rashid SA

Pak J Pharm Sci, 2020 May;33(3):1057-1061.
PMID: 33191229

Recent years, the prevalence of paracetamol allergy becomes great concerns. However, data on knowledge, attitude and perception towards allergic reactions of paracetamol are lacking. This study aimed to investigate knowledge, attitude, and perception towards allergic reactions of paracetamol (KAP-ARP). A cross-sectional survey was conducted using a validated self-administered questionnaire around Pasar Siti Khadijah, Kelantan from February 2016 to January 2017 among the general population. A total of 177 respondents participated in this study. The mean percentage scores for knowledge, attitude and perception towards allergic reactions of paracetamol were 31.7% (SD 23.6), 53.1% (SD 19.2) and 53.3% (SD 23.9), respectively. This study revealed that respondents demonstrated a poor level of knowledge, a fair level of attitude and negative perception towards allergic reactions of paracetamol. These results may lay a basis for conducting a study of knowledge, attitude and perception towards allergic reactions among general population in other different setting or around Malaysia.
Bioassay-guided isolation of a sesquiterpene lactone of deoxyelephantopin from Elephantopus scaber Linn. active on Trypanosome brucei rhodesience

Zahari Z, Jani NA, Amanah A, Latif MN, Majid MI, Adenan MI

Phytomedicine, 2014 Feb 15;21(3):282-5.
PMID: 24269185 DOI: 10.1016/j.phymed.2013.09.011

Methanolic extracts of 70 Malaysia plants were screened for their in vitro antitrypanosomal activity using Trypanosome brucei rhodesience, strain STIB 900 and mouse skeletal cell (L-6) in cytotoxicity activity assay. Results indicated that methanol extract from Elephantopus scaber Linn. (E. scaber) possessed the highest value of antitrypanosomal activity with good selectivity index (antitrypanosomal IC50 of 0.22±0.02 μg/ml, SI value of 204.55). Based on these results, E. scaber was chosen for further study by applying bioassay guided fractionation to isolate its antiprotozoal principle. The antiprotozoal principle was isolated from the ethyl acetate partition through solvent fractionation and crystallization process. The isolated active compound 1 was identified as deoxyelephantopin on the basis of its spectral analysis (FTIR, MS, 1D and 2D NMR).
Fulltext Case series of foreign body aspiration in Paediatric Institute, Hospital Kuala Lumpur

Sahadan DZ, Zainudin NM, Kassim A, Zahari Z, Mahadzir M, Daud CZ, et al.

Med J Malaysia, 2011 Dec;66(5):484-6.
PMID: 22390106 MyJurnal

A retrospective case series was conducted to determine the clinical characteristics and bronchoscopy findings of children with foreign body aspiration in Paediatric Institute, Hospital Kuala Lumpur. Ten boys and two girls were included (range 2-177 months; median 26 months old). They commonly presented with cough (12/100%) and difficulty in breathing (9/75%). All patients had unilateral auscultatory findings and the commonest radiographic findings were unilateral hyperinflation (7/58.3%). The majority of foreign bodies removed was organic (8/66.6%) and more frequently found in the left bronchial tree (7/58.3%). Major complications were pneumonia (11/91.6%) and airway oedema (11/ 91.6%). Eight patients had delayed diagnosis due to parents unawareness (6/50%) and missed diagnosis (2/16.7%).

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