Potentials of additional copper filtration on radiation dose and image quality for adults underwent digital chest X-ray imaging in Dubai Health Authority - UAE.

OBJECTIVE: To explore the potentials of adding copper (Cu) filter on image quality and patient dose of adult patients underwent chest X-ray examination METHODS: Patients were divided into four groups. Group 1, patients were exposed with no added Cu filter (standard or control), group 2 a 0.1 mm Cu filter was added, group 3 acquired with 0.2 mm Cu filter and group 4 performed with 0.3 mm Cu filter. Exposure index (EI), entrance surface dose (ESD) and dose area product (DAP) were recorded from the modality and retrospectively analyzed. The visual grading analysis score (VGAS) was used to evaluate image quality. Mann-Whitney T-Test and one-way ordinary ANOVA Test were used to evaluate statistical differences including gender-based findings. RESULTS: EI, ESD and DAP data for a total of 784 patients (422 male and 362 female) that underwent indirect digital chest radiography exam were collected. Image quality was maintained when adding 0.1 mm Cu filter achieved with ∼19% DAP reduction. Female showed a significant DAP reduction comparing to male registered in the same group. CONCLUSIONS: Reducing dose when using indirect digital chest radiography is possible with no trade-off on image quality. No loss of image quality was reported, images were broadly comparable. IMPLICATIONS FOR PRACTICE: This study highlights the importance of utilizing the additional copper filter in digital chest radiography.

Cost-effectiveness of Denosumab for the Treatment of Postmenopausal Osteoporosis in Malaysia.

From the perspective of Malaysian health care providers, denosumab was cost-effective in the treatment of postmenopausal osteoporosis, with an optimal outcome starting at age 60 years. Our results provide important insights into the value for money of anti-osteoporotic agents that can serve as a reference for other countries with comparable epidemiological data. INTRODUCTION: The study aimed to compare the cost-effectiveness of denosumab with alendronate and no treatment in the management of postmenopausal osteoporosis among the Malaysian population. METHODS: A well-validated Markov model was used to estimate the cost-effectiveness of denosumab in a hypothetical cohort of postmenopausal osteoporotic women between 50 and 80 years old who had no history of fractures. A 10-year time horizon from the perspective of Malaysian health care providers was used in this analysis. The model parameters, including transition probabilities and costs, were based on Malaysian sources. Treatment efficacy data were obtained from a network meta-analysis. The study outcomes were presented as incremental cost per quality-adjusted life-year (QALY) gained. Sensitivity analyses were performed to ensure the robustness of the results. A cost-effectiveness threshold was set at MYR 21,438 (USD 5175) per QALY. RESULTS: Denosumab was found to be a cost-effective option for postmenopausal osteoporotic women aged 60 and older. The incremental cost-effectiveness ratios (ICERs) for denosumab versus alendronate ranged from MYR 16,955 (USD 4093) per QALY at age 60 to MYR 4380 (USD 1057) per QALY at age 80. The cost-effectiveness of denosumab improved monotonically with increasing age. Denosumab was 72.8-92.7% likely to be cost-effective at the cost-effectiveness threshold. Sensitivity analyses demonstrated that the results were robust across all parameter variations, with the annual cost of denosumab being the most sensitive. CONCLUSIONS: From the perspective of the Malaysian health care provider, denosumab appears to be a cost-effective treatment choice for postmenopausal osteoporotic women over 60 years of age.

The Influence of Weather on the Occurrence of Aflatoxin B1 in Harvested Maize from Kenya and Tanzania.

A study was conducted using maize samples collected from different agroecological zones of Kenya (n = 471) and Tanzania (n = 100) during the 2013 maize harvest season to estimate a relationship between aflatoxin B1 concentration and occurrence with weather conditions during the growing season. The toxins were analysed by the ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method. Aflatoxin B1 incidence ranged between 0-100% of samples in different regions with an average value of 29.4% and aflatoxin concentrations of up to 6075 µg/kg recorded in one sample. Several regression techniques were explored. Random forests achieved the highest overall accuracy of 80%, while the accuracy of a logistic regression model was 65%. Low rainfall occurring during the early stage of the maize plant maturing combined with high temperatures leading up to full maturity provide warning signs of aflatoxin contamination. Risk maps for the two countries for the 2013 season were generated using both random forests and logistic regression models.

Factors associated with increased white matter hyperintense lesion (WMHI) load in patients with systemic lupus erythematosus (SLE).

Introduction White matter hyperintense (WMHI) lesions are the most common finding in magnetic resonance imaging (MRI) of the brain in patients with systemic lupus erythematosus (SLE). Objective The objective of this article is to determine the clinical factors associated with an increase in WMHI lesion load among SLE patients. Method A total of 83 SLE patients with MRI of the brain from National University of Malaysia Medical Centre were included. The WMHI lesion load was determined using the Scheltens score and Fazekas scale, and their distribution was divided into the deep white matter (DWMHI) and periventricular (PVH) regions. The clinical correlates of WMHI lesions were initially determined using univariate analyses and subsequently multivariable regression analyses were performed to determine the independent factors of increased WMHI lesion load. Results MRI of the brain of 46 patients who had WMHI lesions were compared with 37 patients with normal MRI. We found significant association between the presence of WMHI lesions and age, presence of cerebral infarcts, positive antiphospholipid antibody (aPL), active disease, neuropsychiatric lupus (NPSLE) and disease damage. Age, SLEDAI scores, cerebral infarcts and disease damage were significantly associated with higher DWMHI and PVH Scheltens scores. Meanwhile, patients with active lupus nephritis (LN), lower serum albumin and more severe proteinuria were associated with larger Fazekas WMHI lesions. Multivariable regression analysis revealed that the independent factors associated with presence of WMHI lesions were positive aPL and SLEDAI scores ( p < 0.05). Higher WMHI Scheltens scores in both DWMHI and PVH were associated with presence of cerebral infarct but higher PVH lesion load was significantly associated with active SLE disease. Conclusion Presence of WMHI lesions in SLE was significantly associated with cerebral infarcts, aPL and high general SLE activity, suggesting both inflammation and ischaemia as the underlying pathology of these lesions.

A descriptive study of the factors associated with damage in Malaysian patients with lupus nephritis.

INTRODUCTION: Renal involvement is the most common serious complication in patients with systemic lupus erythematosus (SLE). OBJECTIVE: The objective of this article is to investigate and determine the associated factors of disease damage among lupus nephritis (LN) patients. METHODS: Medical records of LN patients who attended regular follow-up for at least one year in the Nephrology/SLE Clinic, Universiti Kebangsaan Malaysia Medical Centre (UKMMC), were reviewed. Their Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index scores were noted. Univariate analysis and multivariable regression analysis were performed to determine the independent factors of disease damage in LN. RESULTS: A total of 150 patients were included and their follow-up duration ranged from one to 20 years. Sixty (40%) LN patients had disease damage (SDI ≥1). In the univariate analysis, it was associated with age, longer disease duration, antiphospholipid syndrome (APS), higher maximum daily oral prednisolone dose (mg/day), lower mean C3 and C4, higher chronicity index and global sclerosis on renal biopsies (p < 0.05). Patients who received early (≤3 months after the SLE diagnosis) hydroxychloroquine (HCQ), optimum HCQ dose at 6.5 mg/kg/day and achieved early complete remission (CR) were less likely to have disease damage (p < 0.05). After adjustment for age, gender, disease duration and severity, multivariable regression analysis revealed that a higher maximum daily dose of oral prednisolone was independently associated with disease damage while early HCQ and CR were associated with lower disease damage. CONCLUSION: Higher maximum daily prednisolone dose predicted disease damage whereas treatment with early HCQ and early CR had a protective role against disease damage.

Posterior reversible encephalopathy syndrome in systemic lupus erythematosus: pooled analysis of the literature reviews and report of six new cases.

INTRODUCTION: Posterior reversible encephalopathy syndrome (PRES) is a rare neurological disorder which is increasingly recognized to occur in systemic lupus erythematosus (SLE). OBJECTIVE: The purpose of this study was to identify the characteristics of SLE patients with PRES and the associated factors of the poor outcome among them. METHODS: We investigated SLE patients who developed PRES between 2005-2011 at the Universiti Kebangsaan Malaysia Medical Centre. A comprehensive literature search was done to find all published cases of PRES in SLE. Pooled analysis was conducted to identify the factors associated with poor outcome. RESULTS: There were 103 cases of PRES in SLE published in the literature but only 87 cases were included in the analysis in view of incomplete individual data in the remaining cases. The majority of the cases were Asians (74.2%), female (95.4%) with mean age of 26.3 ± 8.8 years. PRES was highly associated with active disease (97.5%), hypertension (91.7%) and renal involvement (85.1%). We found that 79 patients had a full recovery (90.8%) with a mean onset of full clinical recovery in 5.6 ± 4.1 days. On univariate analysis and logistic regression analysis the predictors of poor outcome, defined as incomplete clinical recovery or death, were intracranial hemorrhage, odds ratio (OR) 14 (1.1-187.2), p=0.04 and brainstem involvement in PRES, OR 10.9 (1.3-90.6), p=0.003. CONCLUSION: Intracranial hemorrhage and brainstem involvement were the two important predictors of poor outcome of PRES. Larger prospective studies are needed to further delineate the risk of poor outcome among them.

Dapson in heterocyclic chemistry part VI: synthesis and molecular docking of some novel sulfonebiscompounds of expected anticancer activity.

To discover new bioactive lead compounds for medicinal purposes, herein, sulfone biscompounds bearing dihydrothiazoles (3-9, 14, 15), acrylamide (11), thiazolidinones (12, 13, 20), thiophenes (16, 17) and benzothiophene (19) were prepared and tested for their anticancer activity. The structures of the products were confirmed from elemental analysis as well as spectral data. All the synthesized compounds showed remarkable anticancer activity against human breast cancer cell line especially, compound (3) with IC50 value 23.02 µM which was better than that of Doxorubicin by three folds. In order to elucidate the mechanism of action of their cytotoxic activity molecular docking on the active sites of farnesyl transferase and arginine methyl transferase was performed for all synthesized compounds and good results were obtained.

Synthesis, anticancer activity and radiosensitizing evaluation of some new 2-pyridone derivatives.

Based on the reported anticancer activity of 2-pyridone, a new series of 6-amino-5-cyano-1-(3-ethylphenyl)-2-oxo-4-substituted-1,2-dihydropyridine-3-carbo-nitriles 4a-p were synthesized and tested for in-vitro anticancer activity against Ehrlich Ascites Carcinoma (EAC) cell line and liver human tumor cell line (HEPG2). Radiosensitizing activity was also evaluated. The starting material 2-cyano-N-(3-ethylphenyl)-acetamide 3 was obtained via reaction of 3-ethyl aniline 1 with ethyl cyanoacetate under condition of fusion. Upon treatment of compound 3 with aromatic aldehyde and malononitrile in the presence of catalytic amount of piperidine yielded the corresponding 1,2-dihydropyridine derivative 4a-p. Also chromenes 5 and 6 were obtained in good yield via reaction of compound 3 with salicyladehyde under different condition. The chromene derivatives 5 and 6 were further reacted with malononitrile in NH4OAc, afford the corresponding chromenopyridones 7 and 8. The structures of the synthesized compounds 3-8 were confirmed by analytical and spectral data. Compounds 4d, 4e, 5 and 6 showed higher anticancer activity against EAC cell line with IC50 values (75.32, 20.77, 73.1 and 67.05 µM) compared to doxorubicin as positive control with IC50 value (68.13 µM), moreover, these compounds showed potent activity on HEPG2 cell line with IC50 values (26.5, 19.2, 39.3, 44.9 µM), respectively, compared to doxorubicin (CAS 29042-30-6) (38.46 µM) and their activity increased synergistically when combined with γ-radiation.

Predictors of thickened carotid intima media thickness among well controlled lupus nephritis patients in a Malaysian tertiary centre.

OBJECTIVES: To investigate the prevalence of thickened carotid intima media thickness (CIMT) and its associated risk factors in patients with lupus nephritis (LN) who were in remission. METHODS: This was a cross sectional study in which consecutive LN patients who were in remission and attending our Nephrology/SLE Clinic were included. Their demographic profile, traditional cardiovascular risk factors and treatment medications were evaluated by clinical interview and review of medical records. Carotid intima media thickness (CIMT) was measured using B Mode carotid ultrasonography. CIMT was considered to be abnormally thickened if it exceeded the 75th percentile matched for age-and sex-matched normal controls. The associated factors for thickened CIMT were examined. RESULTS: A total of 39 patients with a mean remission duration of 29 ± 24.3 months and on a mean prednisolone dose of 9.10 ± 7.83 mg daily completed the study. Six patients (15.4%) had thickened CIMT. On univariate analysis, male gender, patient age, older age at diagnosis, higher serum CRP levels, greater proteinuria and higher mean cumulative azathioprine dose were associated with thickened CIMT (P<0.05). Lower mean cumulative doses of cyclosporine A (CyA) and mycophenolic acid (MPA) (P<0.05) each were associated with thickened CIMT. Using regression analysis, the associated factors of CIMT were older age at diagnosis and proteinuria. CONCLUSIONS: Lupus factors particularly age at diagnosis and proteinuria were the associated factors of thickened CIMT. Larger prospective trials are indicated to confirm our findings.

Loss of PKCδ results in characteristics of Sjögren's syndrome including salivary gland dysfunction.

OBJECTIVES: Chronic infiltration of lymphocytes into the salivary and lacrimal glands of patients with Sjögren's syndrome (SS) leads to destruction of acinar cells and loss of exocrine function. Protein kinase C-delta (PKCδ) is known to play a critical role in B-cell maintenance. Mice in which the PKCδ gene has been disrupted have a loss of B-cell tolerance, multiple organ lymphocytic infiltration, and altered apoptosis. To determine whether PKCδ contributes to the pathogenesis of SS, we quantified changes in indicators of SS in PKCδ-/- mice as a function of age. Salivary gland histology, function, the presence of autoantibodies, and cytokine expression were examined. MATERIALS AND METHODS: Submandibular glands were examined for the presence of lymphocytic infiltrates, and the type of infiltrating lymphocyte and cytokine deposition was evaluated by immunohistochemistry. Serum samples were tested by autoantibody screening, which was graded by its staining pattern and intensity. Salivary gland function was determined by saliva collection at various ages. RESULTS: PKCδ-/- mice have reduced salivary gland function, B220+ B-cell infiltration, anti-nuclear antibody production, and elevated IFN-γ in the salivary glands as compared to PKCδ+/+ littermates. CONCLUSIONS: PKCδ-/- mice have exocrine gland tissue damage indicative of a SS-like phenotype.

Nocardiosis in a patient with rheumatoid arthritis treated with rituximab and a summary of reported cases.

Rituximab is a B-cell-depleting monoclonal anti-CD20 antibody. It is widely used in haematology and rheumatology. However, usage of rituximab in immunosupressed patient has been associated with various opportunistic infections. The authors reported a case of refractory rheumatoid arthritis treated with rituximab, which later presented with non-resolving pneumonia with pulmonary nodule. Percutaneous computer tomogram guided lung biopsy was arranged to confirm the suspicion of tuberculosis, but did not yield conclusive results. Later, she presented left-chest abscess and underwent incision and drainage. The pus culture and sensitivity confirmed pulmonary nocardiosis with chest wall dissemination. She was treated with 2-week course of trimethoprim sulfamethoxazole and responded. The authors also reviewed published cases of nocardiosis post-rituximab.

In-vitro expression of adhesion molecules and bone specific markers are depending on the cell culture material.

Bone formation is an active process whereby osteoblasts are found on the surface of the newly formed bone. Adhesion to extracellular matrix is essential for the development of bone however not all surfaces are suitable for osteoblast adhesion and don't support osteoblastic functions. The objective of this study was to test the suitability of a collagen based microcarrier which would support osteoblastic functions.

Comparative bioavailability study of cefixime (equivalent to 100 mg/5 ml) suspension (Winex vs Suprax) in healthy male volunteers.

This investigation was carried out to evaluate the bioavailability of a new suspension formulation of cefixime (100 mg/5 ml), Winex, relative to the reference product, Suprax (100 mg/5 ml) suspension. The bio-availability study was carried out in 24 healthy male volunteers who received a single oral dose (200 mg) of the test (A) and the reference (B) products on 2 treatment days after an overnight fast of at least 10 hours. The treatment periods were separated by a one-week washout period. A randomized, balanced two-way crossover design was used. After dosing, serial blood samples were collected over a period of 16 hours. Plasma concentrations of cefixime were analyzed using a sensitive high-performance liquid chromatographic assay. The pharmacokinetic parameters for cefixime were determined using standard non-compartmental method. The parameters AUC(0-t), AUC(0-infinity), Cmax, Kel, t1/2 and Cmax/AUC(0-infinity) were analyzed statistically using raw and log-transformed data. The time to maximum concentration (tmax) was analyzed using raw data. The parametric 90% confidence intervals of the mean values of the pnfinity harmacokinetic parameters: AUC(0-t), AUC(0-infinity) Cmax, and Cmax/AUC(0-infinity) were within the range 80 - 125% which is acceptable for bioequivalence (using log-transformed data). The calculated 90% confidence intervals based on the ANOVA analysis for the mean test/reference ratios of AUC(0-t), AUC(0-infinity), Cmax, and Cmax/AUC(0-infinity) were 88.93 - 107.10%, 89.09 - 107.11%, 89.63 - 108.58% and 96.85 - 105.29%, respectively. The test formulation was found bioequivalent to the reference formulation with regard to AUC(0-t), AUC(0-infinity), and Cmax using the Schuirmann's two one-sided t-tests. Therefore, the two formulations were considered to be bioequivalent.

Comparative bioavailability study of doxycycline hyclate (equivalent to 100 mg doxycycline) capsules (doxycin vs vibramycin) for bioequivalence evaluation in healthy adult volunteers.

This investigation was carried out to evaluate the bioavailability of a new capsule formulation of doxycycline (100 mg), doxycin, relative to the reference product, vibramycin (100 mg) capsules. The bioavailability was carried out in 24 healthy male volunteers who received a single dose (100 mg) of the test (A) and the reference (B) products after an overnight fast of at least 10 hours on 2 treatment days. The treatment periods were separated by a 2-week washout period. A randomized, balanced 2-way cross-over design was used. After dosing, serial blood samples were collected for a period of 48 hours. Plasma concentrations of doxycycline were analyzed by a sensitive and validated high-performance liquid chromatography assay. The pharmacokinetic parameters for doxycycline were determined using standard noncompartmental methods. The parameters AUC(0-t), AUC(0-infinity), Cmax, K(el), t(1/2) and Cmax/AUC(0-infinity) were analyzed statistically using log-transformed data. The time to maximum concentration (tmax) was analyzed using raw data. The parametric 90% confidence intervals of the mean values of the pharmacokinetic parameters: AUC(0-t), AUC(0-infinity), Cmax and Cmax/AUC(0-infinity) were within the range 80-125% which is acceptable for bioequivalence (using log-transformed data). The calculated 90% confidence intervals based on the ANOVA analysis of the mean test/reference ratios of AUC(0-t), AUC(0-infinity), Cmax and Cmax/AUC(0-infinity) were 95.98-109.56%, 92.21 to 107.66%, 93.90-112.56%, and 96.0 to 106.91% respectively. The test formulation was found bioequivalent to the reference formulation with regard to AUC(0-t), AUC(0-infinity), Cmax and Cmax/AUC(0-infinity) by the Schuirmann's two 1-sided t-tests. Therefore, the 2 formulations were considered to be bioequivalent.

Hepatoprotective properties of Commiphora opobalsamum ("Balessan"), a traditional medicinal plant of Saudi Arabia.

The hepatoprotective activity of an ethanolic extract of Commiphora opobalsamum ("Balessan") was investigated in rats by inducing hepatotoxicity with carbon tetrachloride:liquid paraffin (1:1). This extract has been shown to possess significant protective effect by lowering serum transaminase levels (serum glutamate oxaloacetate transaminase and serum glutamate pyruvate transaminase), alkaline phosphatase and bilirubin. Pretreatment with an extract of Balessan prevented the prolongation of the barbiturate sleeping time associated with carbon tetrachloride-induced liver damage in mice. On the other hand, CCl4-induced low-level nonprotein sulfhydryl concentration in the liver was replenished by the Balessan extract. These data suggest that the plant C. opobalsamum may act as an antioxidant agent and may have a hepatoprotective effect.

[Epidemiological and clinical studies of ovine caseous lymphadenitis]. / Contribution à l'étude épidémiologique et clinique de la lymphadénite caséeuse chez les ovins.

A field survey was undertaken, to determine epidemiological, clinical and biological data on Ovine Caseous Lymphadenitis disease in 54 flocks originated from Sfax area in Tunisia. The mean morbidity rate of the cutaneous form was 5.1%. This form affected sheep over 3 months and under 2 years old. On the other hand, the mean morbidity rate of the visceral form, encountered in abattoirs, was 11.02%. The clinical aspect of the superficial (or cutaneous) form was often corresponding to one abscess, located particularly in the lymphatic nodes of the animal's head; while visceral (or internal) form of the disease was represented by the presence of a unique abscess found in the pulmonary lymphatic nodes. The macroscopic aspect of lesions showed that the size of abscess was comprised between 4 and 10 cm in diameter. At the cut, colour of the pus was white yellowish to yellow greyish with a fluid or a thick aspect like onion peels; pus was microscopic. Lesions were characterised by a fibrous shell, a pyogenic membrane and a necrotic center. Bacteriological research revealed that Corynebacterium pseudotuberculosis was the pathogen the most frequently isolated, followed by Staphylococcus aureus subsp anaerobius which was particularly found in sheep aged between 3 months and 2 years old.

Daucane sesquiterpenes from Ferula hermonis.

The roots of Ferula hermonis Boiss yielded two new daucane esters, 14-(4'-hydroxybenzoyloxy)dauc-4,8-diene (1) and 14-(4'-hydroxy-3'-methoxybenzoyloxy)dauc-4,8-diene (2), together with the four known sesquiterpenes jaeschkeanadiol p-hydroxybenzoate (3), jaeschkeanadiol benzoate (4), jaeschkeanadiol (5), and epoxyjaeschkeanadiol (6). The identities of the isolated compounds were ascertained primarily using NMR and MS data. Compounds 1 and 3 exhibited antimicrobial activity against Staphylococcus aureus with IC(50) 1.5 and 3.5 microg/mL, respectively, and against Methicillin-resistant S. aureus with IC(50) 2.0 and 4.0 microg/mL, respectively.

New quinoline alkaloids from Ruta chalepensis.

The roots of Ruta chalepensis, collected from the northern Saudi desert, yielded two new quinoline alkaloids, namely, 2-¿6'-(2H-benzo[d]1' ',3' '-dioxolen-5' '-yl)hexyl¿-hydroquinolin-4-one (1) and 2-¿6'-(2H-benzo[d]1' ',3' '-dioxolen-5' '-yl)hexyl¿-4-methoxy-quinoline (2). Nine previously reported alkaloids, dictamnine, pteleine, skimmianine, rutacridone, isogravacridonechlorine, maculosidine, graveoline, graveolinine, and 4-methoxy-1-methyl-2(1H)-quinolinone, and coumarins, chalepensin, and umbelliferone were also isolated. Structure elucidations were based primarily on 1D and 2D NMR analyses and chemical transformations. Antimicrobial activity of these compounds is discussed.

Bioactive 12-oleanene triterpene and secotriterpene acids from Maytenus undata.

The aerial parts of Maytenus undata yielded four new 12-oleanene and 3,4-seco-12-oleanene triterpene acids, namely, 3-oxo-11alpha-methoxyolean-12-ene-30-oic acid (1), 3-oxo-11alpha-hydroxyolean-12-ene-30-oic acid (2), 3-oxo-olean-9(11), 12-diene-30-oic acid (3), and 3,4-seco-olean-4(23),12-diene-3, 29-dioic acid (20-epi-koetjapic acid) (5), together with the known 3, 11-dioxoolean-12-ene-30-oic acid (3-oxo-18beta-glycyrrhetinic acid) (4), koetjapic acid (6), and the 12-oleanene artifact 3-oxo-11alpha-ethoxyolean-12-ene-30-oic acid (7). Koetjapic acid (6) inhibited the growth of Staphylococcus aureus, methicillin-resistant S. aureus, and Pseudomonas aeruginosa, with an MIC range of 3.125-6.25 microg/mL. The new 3,4-secotriterpene acid 20-epi-koetjapic acid (5) potently inhibited rat neonatal brain microglia phorbol ester-stimulated thromboxane B(2) (IC(50) = 0.5 microM) and superoxide anion (IC(50) = 1.9 microM) generation.