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1.  Prevalence of Oral Mucosal Lesions in Patients with Type 2 Diabetes Attending Hospital Universiti Sains Malaysia 
Diabetes mellitus is associated with a greater likelihood of developing certain oral mucosal disorders. This study was aimed at assessing the prevalence of oral mucosal lesions (OMLs) in patients with type 2 diabetes (DM2) and to investigate the association of such lesions with metabolic control of the disease.
This cross-sectional study involved 391 patients with DM2 and 391 non-diabetic control subjects. Demographic information and data on the duration and type of diabetes, glycosylated hemoglobin (HbA1c) values, medical history, and current use of medication were obtained from medical records. Detailed oral examination was performed in accordance with international criteria.
The prevalence of OMLs was significantly higher among diabetic patients (45.5%) than among control subjects (38.4%) (P = 0.042). Patients with diabetes had a higher prevalence of geographic tongue (GT) (P = 0.017), denture stomatitis (P = 0.018), and angular cheilitis (P = 0.006) than controls. Overall, diabetic patients with poor metabolic control had a significantly higher prevalence of OMLs and xerostomia than patients with moderately and well-controlled disease (P < 0.05).
The prevalence of OMLs was significantly higher in diabetic patients than in control subjects. Higher occurrence of OMLs was significantly associated with poor metabolic control.
PMCID: PMC3773351  PMID: 24043995
diabetes mellitus type 2; prevalence; mouth mucosa; oral pathology
2.  Parasitism Performance and Fitness of Cotesia vestalis (Hymenoptera: Braconidae) Infected with Nosema sp. (Microsporidia: Nosematidae): Implications in Integrated Pest Management Strategy 
PLoS ONE  2014;9(6):e100671.
The diamondback moth (DBM) Plutella xylostella (L.) has traditionally been managed using synthetic insecticides. However, the increasing resistance of DBM to insecticides offers an impetus to practice integrated pest management (IPM) strategies by exploiting its natural enemies such as pathogens, parasitoids, and predators. Nevertheless, the interactions between pathogens and parasitoids and/or predators might affect the effectiveness of the parasitoids in regulating the host population. Thus, the parasitism rate of Nosema-infected DBM by Cotesia vestalis (Haliday) (Hym., Braconidae) can be negatively influenced by such interactions. In this study, we investigated the effects of Nosema infection in DBM on the parasitism performance of C. vestalis. The results of no-choice test showed that C. vestalis had a higher parasitism rate on non-infected host larvae than on Nosema-treated host larvae. The C. vestalis individuals that emerged from Nosema-infected DBM (F1) and their progeny (F2) had smaller pupae, a decreased rate of emergence, lowered fecundity, and a prolonged development period compared to those of the control group. DBM infection by Nosema sp. also negatively affected the morphometrics of C. vestalis. The eggs of female C. vestalis that developed in Nosema-infected DBM were larger than those of females that developed in non-infected DBM. These detrimental effects on the F1 and F2 generations of C. vestalis might severely impact the effectiveness of combining pathogens and parasitoids as parts of an IPM strategy for DBM control.
PMCID: PMC4072679  PMID: 24968125
3.  A Giant Juvenile Nasopharyngeal Angiofibroma 
The Journal of craniofacial surgery  2013;24(3):e207-e209.
Juvenile nasopharyngeal angiofibroma (JNA) are locally growing highly vascular tumours. They are treated primarily by surgical excision ranging from open approach to endoscopic approach. We presented a 20-year-old male with a giant nasopharyngeal juvenile angiofibroma obliterating the pterygopalatine fossa bilaterally, invasing the sphenoid bone and extending to the left nasal passage. His complaints were epistaxis and nasal obstruction. After embolization, the patient was treated surgically with endoscopic approach and discharged as cured without any complication.
PMCID: PMC3668308  PMID: 23714961
Juvenile nasopharyngeal angiofibroma; Endoscopic surgery; Bipolar cautery
4.  Indications of Brain Computed Tomography Scan in Children Younger Than 3 Years of Age with Minor Head Trauma 
Objective. To investigate the indications to receive brain computed tomography (CT) scan and to define the pathological findings in children younger than three years of age with minor head trauma in emergency departments. Methods. In this study, hospital case notes of 1350 children attending the emergency department of Bitlis State Hospital between January 2011 and June 2013 were retrospectively reviewed. 508 children under 3 years of age with minor head trauma were included in this study. We also asked 37 physicians about the indications for requiring CT in these children. Results. This study included 508 children, 233 (45,9%) of whom were female and 275 were male. In 476 (93,7%) children, the brain CT was completely normal. 89,2% of physicians asked in the emergency department during that time interval reported that they requested CT scan to protect themselves against malpractice litigation. Conclusion. In infants and children with minor head trauma, most CT scans were unnecessary and the fear of malpractice litigation of physicians was the most common reason for requesting a CT.
PMCID: PMC3958781  PMID: 24724031
5.  Induction of apoptosis through oxidative stress-related pathways in MCF-7, human breast cancer cells, by ethyl acetate extract of Dillenia suffruticosa 
Breast cancer is one of the most dreading types of cancer among women. Herbal medicine has becoming a potential source of treatment for breast cancer. Herbal plant Dillenia suffruticosa (Griff) Martelli under the family Dilleniaceae has been traditionally used to treat cancerous growth. In this study, the anticancer effect of ethyl acetate extract of D. suffruticosa (EADs) was examined on human breast adenocarcinoma cell line MCF-7 and the molecular pathway involved was elucidated.
EADs was obtained from the root of D. suffruticosa by using sequential solvent extraction. Cytotoxicity was determined by using MTT assay, mode of cell death by cell cycle analysis and apoptosis induction by Annexin-FITC/PI assay. Morphology changes in cells were observed under inverted light microscope. Involvement of selected genes in the oxidative stress-mediated signaling pathway was explored using multiplex gene expression analysis.
The treatment of EADs caused cytotoxicity to MCF-7 cells in a dose- and time-dependent manner at 24, 48 and 72 hours with IC50 of 76 ± 2.3, 58 ± 0.7 and 39 ± 3.6 μg/mL, respectively. The IC50 of tamoxifen-treated MCF-7 cells was 8 ± 0.5 μg/mL. Induction of apoptosis by EADs was dose- and time- dependent. EADs induced non-phase specific cell cycle arrest at different concentration and time point. The multiplex mRNA expression study indicated that EADs-induced apoptosis was accompanied by upregulation of the expression of SOD1, SOD2, NF-κB, p53, p38 MAPK, and catalase, but downregulation of Akt1.
It is suggested that EADs induced apoptosis in MCF-7 cells by modulating numerous genes which are involved in oxidative stress pathway. Therefore, EADs has the potential to act as an effective intervention against breast cancer cells.
PMCID: PMC3927215  PMID: 24524627
Dillenia suffruticosa; Breast cancer; Cytotoxic; Apoptosis; Oxidative stress pathway
6.  Effect of pheniramine maleate on reperfusion injury in brain tissue 
The aim of this study was to investigate the protective effects of methylprednisolone (Pn), which is a potent anti-inflammatory agent, and pheniramine maleate (Ph), which is an antihistaminic with some anti-inflammatory effects, on reperfusion injury in brain developing after ischemia of the left lower extremity of rats.
Twenty-eight randomly selected male Sprague-Dawley rats were divided into 4 groups: Group 1 was the control group, Group 2 was the sham group (I/R), Rats in Group 3 were subjected to I/R and given Ph, and rats in Group 4 were subjected to I/R and given Pn. A tourniquet was applied at the level of left groin region of subjects in the I/R group after induction of anesthesia. One h of ischemia was performed with no drug administration. In the Ph group, half of a total dose of 10 mg/kg Ph was administered intraperitoneally before ischemia and the remaining half before reperfusion. In the Pn group, subjects received a single dose of 50 mg/kg Pn intraperitoneally at the 30th min of ischemia. Brains of all subjects were removed after 24 h for examination.
Malondialdehyde (MDA) levels of the prefrontal cortex were significantly lower in the Ph group than in the I/R group (p<0.05). Superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzyme activities were found to be significantly higher in the Ph group than in the I/R group (p<0.05). Histological examination demonstrated that Ph had protective effects against I/R injury developing in the brain tissue.
Ph has a protective effect against ischemia/reperfusion injury created experimentally in rat brains.
PMCID: PMC3867399  PMID: 24309384
ischemia/reperfusion injury; pheniramine maleate; brain
7.  Generating temporal model using climate variables for the prediction of dengue cases in Subang Jaya, Malaysia 
To develop a forecasting model for the incidence of dengue cases in Subang Jaya using time series analysis.
The model was performed using the Autoregressive Integrated Moving Average (ARIMA) based on data collected from 2005 to 2010. The fitted model was then used to predict dengue incidence for the year 2010 by extrapolating dengue patterns using three different approaches (i.e. 52, 13 and 4 weeks ahead). Finally cross correlation between dengue incidence and climate variable was computed over a range of lags in order to identify significant variables to be included as external regressor.
The result of this study revealed that the ARIMA (2,0,0) (0,0,1)52 model developed, closely described the trends of dengue incidence and confirmed the existence of dengue fever cases in Subang Jaya for the year 2005 to 2010. The prediction per period of 4 weeks ahead for ARIMA (2,0,0)(0,0,1)52 was found to be best fit and consistent with the observed dengue incidence based on the training data from 2005 to 2010 (Root Mean Square Error=0.61). The predictive power of ARIMA (2,0,0) (0,0,1)52 is enhanced by the inclusion of climate variables as external regressor to forecast the dengue cases for the year 2010.
The ARIMA model with weekly variation is a useful tool for disease control and prevention program as it is able to effectively predict the number of dengue cases in Malaysia.
PMCID: PMC4027327
Dengue; Forecasting; ARIMA model; Climate; Malaysia
8.  Noise-Induced Hearing Loss Among Quarry Workers in a North-Eastern State of Malaysia: A Study on Knowledge, Attitude and Practice 
Oman Medical Journal  2013;28(5):331-336.
Noise is known to be one of the environmental and occupational hazards listed in the Factory and Machinery Act 1967. Quarries with loud deafening sounds from trucks and machineries pose the risk of noise-induced hearing loss to workers. This study was designed to assess the knowledge, attitude and practice towards noise-induced hearing loss and to determine the prevalence of noise-induced hearing loss and its associated factors among quarry workers in a north-eastern state of Malaysia.
A cross-sectional study was conducted at six quarries in a north-eastern state of Malaysia, with 97 consented respondents who answered a validated version of a questionnaire and underwent pure tone audiogram. The respondents were male, aged between 18 to 50 years, working in the quarry area for at least 6-months duration with no family history of ear diseases.
The mean percentage scores of knowledge, attitude and practice were 44 (11), 70 (10) and 28 (16) percent, respectively. The prevalence of noise-induced hearing loss was found to be 57 (95% CI: 47, 67) with 46 (84%) having mild and moderate noise-induced hearing loss, and 34 (62%) involved both ears. Multiple logistic regressions showed that age and practice score were the associated factors with odd ratios of 1.1 (95% CI: 1.1, 1.2; p<0.001) and 0.9 (95% CI: 0.8, 1.0; p=0.008), respectively.
The knowledge, attitude and practice scores of the respondents were poor and the high prevalence of noise-induced hearing loss was contributed by factors such as poor practice and old age.
PMCID: PMC3769125  PMID: 24044059
Noise-induced hearing loss; Knowledge, attitude and practice; Prevalence; Quarry workers
9.  Ethyl acetate extract of germinated brown rice attenuates hydrogen peroxide-induced oxidative stress in human SH-SY5Y neuroblastoma cells: role of anti-apoptotic, pro-survival and antioxidant genes 
There are reports of improved metabolic outcomes due to consumption of germinated brown rice (GBR). Many of the functional effects of GBR can be linked to its high amounts of antioxidants. Interestingly, dietary components with high antioxidants have shown promise in the prevention of neurodegenerative diseases like Alzheimer’s disease (AD). This effect of dietary components is mostly based on their ability to prevent apoptosis, which is believed to link oxidative damage to pathological changes in AD. In view of the rich antioxidant content of GBR, we studied its potential to modulate processes leading up to AD.
The total phenolic content and antioxidant capacity of the ethyl acetate extract of GBR were compared to that of brown rice (BR), and the cytotoxicity of both extracts were determined on human SH-SY5Y neuronal cells using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) Assay. Based on its higher antioxidant potentials, the effect of the GBR extract on morphological changes due to hydrogen peroxide (H2O2)-induced oxidative damage in human SH-SY5Y neuronal cells was examined using inverted light microscope and fluorescence microscope by means of acridine orange-propidium iodide (AO/PI) staining. Also, evaluation of the transcriptional regulation of antioxidant and apoptotic genes was carried out using Multiplex Gene Expression System.
The ethyl acetate extract of GBR had higher total phenolic content and antioxidant capacity compared to BR. The cytotoxicity results showed that GBR extract did not cause any damage to the human SH-SY5Y neuronal cells at concentrations of up to 20 ppm, and the morphological analyses showed that the GBR extract (up to 10 ppm) prevented H2O2-induced apoptotic changes in the cells. Furthermore, multiplex gene expression analyses showed that the protection of the cells by the GBR extract was linked to its ability to induce transcriptional changes in antioxidant (SOD 1, SOD 2 and catalase) and apoptotic (AKT, NF-Kβ, ERK1/2, JNK, p53 and p38 MAPK) genes that tended towards survival.
Taken together, the results of our study showed that the ethyl acetate extract of GBR, with high antioxidant potentials, could prevent H2O2-induced oxidative damage in SH-SY5Y cells. The potential of GBR and its neuroprotective mechanism in ameliorating oxidative stress-related cytotoxicity is therefore worth exploring further.
PMCID: PMC3726323  PMID: 23866310
Germinated brown rice; Antioxidant; Oxidative stress; Neuroprotective; SH-SY5Y
10.  Cytotoxic Activity of Kenaf Seed Oils from Supercritical Carbon Dioxide Fluid Extraction towards Human Colorectal Cancer (HT29) Cell Lines 
Kenaf (Hibiscus cannabinus) from the family Malvaceae, is a valuable fiber plant native to India and Africa and is currently planted as the fourth commercial crop in Malaysia. Kenaf seed oil contains alpha-linolenic acid, phytosterol such as β-sitosterol, vitamin E, and other antioxidants with chemopreventive properties. Kenaf seeds oil (KSO) was from supercritical carbon dioxide extraction fluid (SFE) at 9 different permutations of parameters based on range of pressures from 200 to 600 bars and temperature from 40 to 80°C. They were 200/40, 200/60, 200/80, 400/40, 400/60, 400/80, 600/40, 600/60, and 600/80. Extraction from 9 parameters of KSO-SFE was screened for cytotoxicity towards human colorectal cancer cell lines (HT29) and mouse embryonic fibroblast (NIH/3T3) cell lines using MTS assay. KSO-SFE at 600/40 showed the strongest cytotoxicity towards HT29 with IC50 of 200 µg/mL. The IC50 for NIH/3T3 was not detected even at highest concentration employed. Cell cycle analysis showed a significant increase in the accumulation of KSO-SFE-treated cells at sub-G1 phase, indicating the induction of apoptosis by KSO-SFE. Further apoptosis induction was confirmed by Annexin V/PI and AO/PI staining.
PMCID: PMC3626181  PMID: 23606884
11.  Gender, airborne chemical monitoring, and physical work environment are related to indoor air symptoms among nonindustrial workers in the Klang Valley, Malaysia 
The purpose of this study was to analyze the relationship of airborne chemicals and the physical work environment risk element on the indoor air symptoms of nonindustrial workers.
A cross-sectional study consisting of 200 office workers. A random selection of 200 buildings was analyzed for exposure and indoor air symptoms based on a pilot study in the Klang Valley, Malaysia.
A set of modified published questionnaires by the Department of Occupational Safety and Health (DOSH), Malaysia and a previous study (MM040NA questionnaire) pertaining to indoor air symptoms was used in the evaluation process of the indoor air symptoms. Statistical analyses involving logistic regression and linear regression were used to determine the relationship between exposure and indoor air symptoms for use in the development of an indoor risk matrix.
The results indicate that some indoor air pollutants (carbon monoxide, formaldehyde, total volatile organic compound, and dust) are related to indoor air symptoms of men and women. Temperature and relative humidity showed a positive association with complaints related to the perceived indoor environmental condition (drafts and inconsistency of temperature). Men predominantly reported general symptoms when stratification of gender involved exposure to formaldehyde. Women reported high levels of complaints related to mucosal and general symptoms from exposure to the dust level indoors.
Exposure to pollutants (total volatile organic compounds, carbon monoxide, and formaldehyde) and physical stressors (air temperature and relative humidity) influence reported symptoms of office workers. These parameters should be focused upon and graded as one of the important elements in the grading procedure when qualitatively evaluating the indoor environment.
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PMCID: PMC3596155  PMID: 23526736
sick building syndrome (SBS); regression analysis; environmental climate factor; occupational exposure; asthma; allergy
12.  Sedation depth and long-term mortality in mechanically ventilated critically ill adults: a prospective longitudinal multicentre cohort study 
Intensive Care Medicine  2013;39(5):910-918.
To ascertain the relationship among early (first 48 h) deep sedation, time to extubation, delirium and long-term mortality.
We conducted a multicentre prospective longitudinal cohort study in 11 Malaysian hospitals including medical/surgical patients (n = 259) who were sedated and ventilated ≥24 h. Patients were followed from ICU admission up to 28 days in ICU with 4-hourly sedation and daily delirium assessments and 180-day mortality. Deep sedation was defined as Richmond Agitation Sedation Score (RASS) ≤−3.
The cohort had a mean (SD) age of 53.1 (15.9) years and APACHE II score of 21.3 (8.2) with hospital and 180-day mortality of 82 (31.7 %) and 110/237 (46.4 %). Patients were followed for 2,657 ICU days and underwent 13,836 RASS assessments. Midazolam prescription was predominant compared to propofol, given to 241 (93 %) versus 72 (28 %) patients (P < 0.0001) for 966 (39.6 %) versus 183 (7.5 %) study days respectively. Deep sedation occurred in (182/257) 71 % patients at first assessment and in 159 (61 %) patients and 1,658 (59 %) of all RASS assessments at 48 h. Multivariable Cox proportional hazard regression analysis adjusting for a priori assigned covariates including sedative agents, diagnosis, age, APACHE II score, operative, elective, vasopressors and dialysis showed that early deep sedation was independently associated with longer time to extubation [hazard ratio (HR) 0.93, 95 % confidence interval (CI) 0.89–0.97, P = 0.003], hospital death (HR 1.11, 95 % CI 1.05–1.18, P < 0.001) and 180-day mortality (HR 1.09, 95 % CI 1.04–1.15, P = 0.002), but not time to delirium (HR 0.98, P = 0.23). Delirium occurred in 114 (44 %) of patients.
Irrespective of sedative choice, early deep sedation was independently associated with delayed extubation and higher mortality, and thus was a potentially modifiable risk in interventional trials.
PMCID: PMC3625407  PMID: 23344834
Sedation depth; Mechanical ventilation; Delirium; Critically ill; Mortality
13.  Statistical Methods Used to Test for Agreement of Medical Instruments Measuring Continuous Variables in Method Comparison Studies: A Systematic Review 
PLoS ONE  2012;7(5):e37908.
Accurate values are a must in medicine. An important parameter in determining the quality of a medical instrument is agreement with a gold standard. Various statistical methods have been used to test for agreement. Some of these methods have been shown to be inappropriate. This can result in misleading conclusions about the validity of an instrument. The Bland-Altman method is the most popular method judging by the many citations of the article proposing this method. However, the number of citations does not necessarily mean that this method has been applied in agreement research. No previous study has been conducted to look into this. This is the first systematic review to identify statistical methods used to test for agreement of medical instruments. The proportion of various statistical methods found in this review will also reflect the proportion of medical instruments that have been validated using those particular methods in current clinical practice.
Five electronic databases were searched between 2007 and 2009 to look for agreement studies. A total of 3,260 titles were initially identified. Only 412 titles were potentially related, and finally 210 fitted the inclusion criteria. The Bland-Altman method is the most popular method with 178 (85%) studies having used this method, followed by the correlation coefficient (27%) and means comparison (18%). Some of the inappropriate methods highlighted by Altman and Bland since the 1980s are still in use.
This study finds that the Bland-Altman method is the most popular method used in agreement research. There are still inappropriate applications of statistical methods in some studies. It is important for a clinician or medical researcher to be aware of this issue because misleading conclusions from inappropriate analyses will jeopardize the quality of the evidence, which in turn will influence quality of care given to patients in the future.
PMCID: PMC3360667  PMID: 22662248
14.  CBX4-mediated SUMO modification regulates BMI1 recruitment at sites of DNA damage 
Nucleic Acids Research  2012;40(12):5497-5510.
Polycomb group (PcG) proteins are involved in epigenetic silencing where they function as major determinants of cell identity, stem cell pluripotency and the epigenetic gene silencing involved in cancer development. Recently numerous PcG proteins, including CBX4, have been shown to accumulate at sites of DNA damage. However, it remains unclear whether or not CBX4 or its E3 sumo ligase activity is directly involved in the DNA damage response (DDR). Here we define a novel role for CBX4 as an early DDR protein that mediates SUMO conjugation at sites of DNA lesions. DNA damage stimulates sumoylation of BMI1 by CBX4 at lysine 88, which is required for the accumulation of BMI1 at DNA damage sites. Moreover, we establish that CBX4 recruitment to the sites of laser micro-irradiation-induced DNA damage requires PARP activity but does not require H2AX, RNF8, BMI1 nor PI-3-related kinases. The importance of CBX4 in the DDR was confirmed by the depletion of CBX4, which resulted in decreased cellular resistance to ionizing radiation. Our results reveal a direct role for CBX4 in the DDR pathway.
PMCID: PMC3384338  PMID: 22402492
15.  Neuroprotective Effects of Germinated Brown Rice against Hydrogen Peroxide Induced Cell Death in Human SH-SY5Y Cells 
The neuroprotective and antioxidative effects of germinated brown rice (GBR), brown rice (BR) and commercially available γ-aminobutyric acid (GABA) against cell death induced by hydrogen peroxide (H2O2) in human neuroblastoma SH-SY5Y cells have been investigated. Results show that GBR suppressed H2O2-mediated cytotoxicity and induced G0/G1 phase cell cycle arrest in SH-SY5Y cells. Moreover, GBR reduced mitochondrial membrane potential (MMP) and prevented phosphatidylserine (PS) translocation in SH-SY5Y cells, key features of apoptosis, and subsequent cell death. GBR exhibited better neuroprotective and antioxidative activities as compared to BR and GABA. These results indicate that GBR possesses high antioxidative activities and suppressed cell death in SH-SY5Y cells by blocking the cell cycle re-entry and apoptotic mechanisms. Therefore, GBR could be developed as a value added functional food to prevent neurodegenerative diseases caused by oxidative stress and apoptosis.
PMCID: PMC3431823  PMID: 22949825
germinated brown rice; γ-aminobutyric acid; hydrogen peroxide; neuroprotective; SH-SY5Y cell death
16.  BMI1-mediated histone ubiquitylation promotes DNA double-strand break repair 
The Journal of Cell Biology  2010;191(1):45-60.
The polycomb repressor complex ubiquitylates γ-H2AX and other components of the DNA damage response pathway to facilitate genomic repair.
Polycomb group (PcG) proteins are major determinants of cell identity, stem cell pluripotency, and epigenetic gene silencing during development. The polycomb repressive complex 1, which contains BMI1, RING1, and RING2, functions as an E3-ubuiquitin ligase. We found that BMI1 and RING2 are recruited to sites of DNA double-strand breaks (DSBs) where they contribute to the ubiquitylation of γ-H2AX. In the absence of BMI1, several proteins dependent on ubiquitin signaling, including 53BP1, BRCA1, and RAP80, are impaired in recruitment to DSBs. Loss of BMI1 sensitizes cells to ionizing radiation to the same extent as loss of RNF8. The simultaneous depletion of both proteins revealed an additive increase in radiation sensitivity. These data uncover an unexpected link between the polycomb and the DNA damage response pathways, and suggest a novel function for BMI1 in maintaining genomic stability.
PMCID: PMC2953429  PMID: 20921134
17.  Adenomatous Colorectal Polyps in Patients Referred for Colonoscopy in a Regional Hospital in Kuwait 
Adenomatous colorectal polyps (ACPs) are known to be the precursor lesions for colorectal cancer. The aim of the study was to determine the prevalence, endoscopic and pathological features of ACPs in patients referred for colonoscopy.
Patients and Methods:
The endoscopic and histological reports of adult patients who underwent complete colonoscopy in the gastroenterology unit of a regional Kuwaiti hospital between January 2008 and December 2008 were retrospectively studied. The specimens of polyps were reviewed by an experienced pathologist who was blinded to the clinical or endoscopic information. Non-neoplastic polyps were not included in the analysis.
Of 530 eligible patients (mean age, 45 years; male-female ratio, 2:1), 54 (10%) had 103 ACPs. Of the patients with ACPs (mean age, 57 years), 43 (80%) were males and 36 (67%) were Kuwaitis. Histopathological examination of the most significant polyp in each patient revealed that 40 (74%) polyps were tubular adenomas (TAs); 11 (20%), tubulovillous (TV) adenomas; and 3 (6%), villous adenomas. High-grade dysplasia was noticed in 4 (10%) adenomas. Fifteen (2.8%) of the 530 patients had advanced ACPs. Logistic regression analysis of some variables and their association with ACPs found that age (P<0.001; OR, 1.9; CI, 1.5-2.3), history of adenoma (P=0.001; OR, 6.4; CI, .2.1-19.4) and being Kuwaitis (P=0.029; OR, 2.1; CI, 1.1-4.1) to be independently associated with ACPs.
The most common histological type of ACPs was tubular adenoma. Advancing age, being Kuwaiti nationals and prior removal of ACPs were significantly associated with the occurrence of ACPs.
PMCID: PMC3003207  PMID: 20616414
Colonoscopy; colorectal polyps; Kuwait
18.  Effect of rosiglitazone and ramipril on macrovasculopathy in patients with type 2 diabetes: needs longer treatment and/or higher doses? 
The aim of the study is to investigate whether standard doses of rosiglitazone (4 mg/daily) and ramipril (5 mg/daily) can reverse pre-clinical macrovasculopathy in newly diagnosed never treated type 2 diabetes (T2DM) patients.
In this randomized, double-blind, placebo-controlled study, 33 T2DM patients were randomized to rosiglitazone (4 mg/daily) or ramipril (5 mg/daily) or placebo for 1 year. Hemodynamic variables were measured at 3 treatment phases and pulse wave velocity (PWV) and augmentation index (AI) were measured throughout the treatment period.
In diabetic patients, PWV (P = 0.037) and AI (P = 0.005) with ramipril and AI (P < 0.001) with rosiglitazone were significantly reduced during overall treatment period from the baseline; however, these differences were not significant in comparison to placebo.
Discussion and conclusion
The present study showed that treatment with standard doses of rosiglitazone and ramipril are not adequate to reverse pre-clinical vasculopathy in T2DM. The lack of benefit in newly diagnosed T2DM may be because of the relatively short-term intervention and/or the use of lower doses of rosiglitazone/ramipril. Further trials are needed for a longer period of time, possibly with higher doses, to show whether rosiglitazone/ramipril can reverse pre-clinical vasculopathy in T2DM ( number, NCT00489229).
PMCID: PMC3262381  PMID: 22291490
rosiglitazone; ramipril; diabetic vasculopathy
19.  Tooth Wear Prevalence and Sample Size Determination : A Pilot Study 
Tooth wear is the non-carious loss of tooth tissue, which results from three processes namely attrition, erosion and abrasion. These can occur in isolation or simultaneously. Very mild tooth wear is a physiological effect of aging. This study aims to estimate the prevalence of tooth wear among 16-year old Malay school children and determine a feasible sample size for further study. Fifty-five subjects were examined clinically, followed by the completion of self-administered questionnaires. Questionnaires consisted of socio-demographic and associated variables for tooth wear obtained from the literature. The Smith and Knight tooth wear index was used to chart tooth wear. Other oral findings were recorded using the WHO criteria. A software programme was used to determine pathological tooth wear. About equal ratio of male to female were involved. It was found that 18.2% of subjects have no tooth wear, 63.6% had very mild tooth wear, 10.9% mild tooth wear, 5.5% moderate tooth wear and 1.8 % severe tooth wear. In conclusion 18.2% of subjects were deemed to have pathological tooth wear (mild, moderate & severe). Exploration with all associated variables gave a sample size ranging from 560 – 1715. The final sample size for further study greatly depends on available time and resources.
PMCID: PMC3341919  PMID: 22589636
pilot study; tooth wear; prevalence and sample size determination
20.  Comparison of Plateletpheresis on the Fenwal Amicus and Fresenius Com.Tec Cell Separators 
A variety of apheresis devices are now available on the market for plateletapheresis. We compared two apheresis instruments (Fenwal Amicus and Fresenius COM.TEC) with regard to processing time, platelet (PLT) yield and efficiency, and white blood cell (WBC) content.
Material and Methods
Donors undergoing plateletpheresis were randomly separated into two groups (either the Amicus or the COM.TEC cell separator).
In the pre-apheresis setting, 32 plateletpheresis procedures performed with each instrument revealed no significant differences in donors’ sex, age, weight, height and total blood volume between the two groups. However, the pre-apheresis PLT count was higher with the COM.TEC than with the Amicus (198 × 103/μl vs. 223 × 103/μl; p = 0.035). The blood volume processed to reach a target PLT yield of ≥3.3 × 1011 was higher in the COM.TEC compared to the Amicus (3,481 vs. 2,850 ml; p < 0.001). The median separation time was also significantly longer in the COM.TEC than in the Amicus (61 vs. 44 min; p < 0.001). 91 and 88% of the PLT products collected with the Amicus and the COM.TEC, respectively, had a PLT count of >3.3 × 1011 (p = 0.325). All products obtained with both instruments had WBC counts lower than 5 ↔ 106, as required. There was no statistical difference with regard to collection efficiency between the devices (55 ± 15 vs. 57 ± 15%; p = 0.477). However, the collection rate was significantly higher with the Amicus compared to the COM.TEC instrument (0.077 ± 0.012 × 1011 vs. 0.057 ± 0.008 × 1011 PLT/min; p < 0.001).
Both instruments collected platelets efficiently. Additionally, consistent leukoreduction was obtained with both instruments; however, compared with the COM.TEC instrument, the Amicus reached the PLT target yield more quickly.
PMCID: PMC3076329  PMID: 21512626
Plateletpheresis; Apheresis; Amicus; COM.TEC; Cell separator
21.  An optimized method for detecting gamma-H2AX in blood cells reveals a significant interindividual variation in the gamma-H2AX response among humans 
Nucleic Acids Research  2007;35(5):e36.
Phosphorylation of histone H2AX on serine 139 (gamma-H2AX, γH2AX) occurs at sites flanking DNA double-strand breaks (DSBs) and can provide a measure of the number of DSBs within a cell. Here we describe a rapid and simple flow-cytometry-based method, optimized to measure gamma-H2AX in non-fixed peripheral blood cells. No DSB induced signal was observed in H2AX−/− cells indicating that our FACS method specifically recognized gamma-H2AX accumulation. The gamma-H2AX assay was capable of detecting DNA damage at levels 100-fold below the detection limit of the alkaline comet assay. The gamma-H2AX signal was quantitative with a linear increase of the gamma-H2AX signal over two orders of magnitude. We found that all nucleated blood cell types examined, including the short-lived neutrophils induce gamma-H2AX in response to DSBs. Interindividual difference in the gamma-H2AX signal in response to ionizing radiation and the DSB-inducing drug calicheamicin was almost 2-fold in blood cells from patients, indicating that the amount of gamma-H2AX produced in response to a given dose of radiation varies significantly in the human population. This simple method could be used to monitor response to radiation or DNA-damaging drugs.
PMCID: PMC1865071  PMID: 17284459
22.  A Cross-Sectional Study of Soft Tissue Facial Morphometry in Children and Adolescents 
The aim of this study was to determine mean values for selected linear measurements on the face of children and adolescents to demonstrate gender differences in the measurements. Cross-sectional data from 262 school children (158 male, 104 female) aged between 6 and 15 years were taken by measuring certain identified facial landmarks using a sliding caliper. The landmarks were first located by careful inspection and/or palpation of the face and a mark created on the cutaneous surface, with the subject sitting in habitual occlusion in an upright position. A sliding caliper was used to measure the distances between the points. The data was analysed using SPSS version 10.0 to determine mean values, standard deviation and gender differences in the measurements. Upper facial heights, total facial height, inter-canthal distance and eye length measurements were significantly higher in male than in female for 15-year-old group (p<0.0001). The measurement between the highest and the lowest point of attachment of external ear to the head was significantly larger in male than in female for 11 year old age group.
PMCID: PMC3347899  PMID: 22589587
facial growth; soft tissue facial morphometry
23.  Pubertal immune challenge blocks the ability of estradiol to enhance performance on cognitive tasks in adult female mice 
Psychoneuroendocrinology  2012;38(7):1170-1177.
Puberty is a period characterized by brain reorganization that contributes to the development of neural and behavioral responses to gonadal steroids. Previously, we have shown that a single injection of the bacterial endotoxin, lipopolysaccharide (LPS; 1.5mg/kg IP), during the pubertal period (around 6 weeks old) in mice decreases sexual receptivity in response to estradiol and progesterone in adulthood. These findings suggest that pubertal immune challenge has an enduring effect of decreasing the behavioral responsiveness to gonadal steroid hormones. Since estradiol improves cognitive function in certain tasks in mice, we investigated the effect of pubertal immune challenge on the ability of estradiol to enhance cognitive function. We hypothesized that estradiol would be less effective at enhancing performance on particular cognitive tasks in female mice treated with LPS during puberty. Six-week old (pubertal) and ten-week old (adult) female CD1 mice were injected with either saline or LPS. Five weeks later, they were ovariectomized and implanted subcutaneously with either an estradiol- or oil-filled Silastic© capsule followed one week later with testing for cognitive function. The duration of juvenile investigation during social discrimination and recognition tests was used as a measure of social memory, and the duration of object investigation during object recognition and placement tests was used as a measure of object memory. Chronic estradiol treatment enhanced social and object memory in saline-treated females and in females treated with LPS in adulthood. In contrast, in females treated with LPS at 6 weeks old, estradiol failed to improve social and object memories. These results support the hypothesis that exposure to an immune challenge during puberty reduces at least some of the cognitive effects of estradiol. Moreover, these results support the idea that pubertal immune challenge compromises a wide variety of behavioral influences of ovarian hormones.
PMCID: PMC3604046  PMID: 23218519
Estradiol; hippocampus-dependent tasks; immune challenge; puberty
24.  Dopamine D2/3 occupancy of ziprasidone across a day: a within-subject PET study 
Psychopharmacology  2013;228(1):43-51.
Ziprasidone is an atypical antipsychotic recommended to be administered twice daily.
The purpose of this study was to investigate whether occupancy of the dopamine D2/3 receptors by ziprasidone is maintained across a day employing a within subject design.
Positron Emission Tomography (PET) scans with [11C]-raclopride were performed in 12 patients with schizophrenia while treated with ziprasidone 60mg twice daily. Each patient completed [11C]-raclopride PET scans at 5, 13 and 23 hours after the last dose of ziprasidone. Dopamine D2/3 receptor occupancy was estimated with reference to binding potential data of 44 age- and sex-matched control subjects in the caudate, putamen and ventral striatum.
Eleven scans were available at each time point, and the mean occupancies at 5-, 13- and 23-hour scans were 66%, 39% and 2% in the putamen; 62%, 35% and −6% in the caudate; and 68%, 47% and 11% in the ventral striatum, respectively. The time-course of receptor occupancy across the regions indicated an occupancy half-life of 8.3 hours. The serum level of ziprasidone associated with 50% D2/3 receptors occupancy was estimated to be 204nmol/L (84ng/ml). Prolactin levels were highest at 5-hour post-dose and none showed hyperprolactinemia at 23-hour scans.
The absence of ziprasidone striatal D2/3 receptor binding 23-hour after taking 60 mg under steady state conditions is consistent with its peripheral half-life. The results support our earlier report that ziprasidone 60 mg administered twice daily appears to be the minimal dose expected to achieve therapeutic central dopamine D2 receptor occupancy (i.e. 60%).
PMCID: PMC3679209  PMID: 23417515
[11C]-raclopride; dopamine D2 receptor; pharmacokinetics; Positron Emission Tomography; schizophrenia; ziprasidone
25.  Enduring influence of pubertal stressors on behavioral response to hormones in female mice 
Hormones and behavior  2013;64(2):390-398.
The pubertal period is a time of change in an animal’s response to stress, and it is a second period of sexual differentiation of the brain. Recently, it was discovered that particular stressors during the prolonged pubertal period of female mice result in enduring changes in behavioral responsiveness of the brain to estradiol and progesterone. Depending on the behavior, pubertal immune challenge or shipping from suppliers may decrease, eliminate, or even reverse the effects of estradiol. Pubertal immune challenge results in changes in the number of estrogen receptor-immunoreactive cells in key brain areas suggesting a cellular mechanism for this remodeling of the brain’s response to hormones. A hypothesis is put forward that predicts that particular adverse experiences in girls may cause long-term alterations in the brain’s response to estradiol and/or progesterone via activation of the immune system. This could lead to mood disorders or altered response to any behavior influenced by estradiol in humans.
PMCID: PMC3761225  PMID: 23998680
Stress; Immune Challenge; Lipopolysaccharide; Depression; Anxiety; Cognitive function; Sexual behavior; Estradiol; Progesterone; Puberty; Females; Mood disorders

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