Postoperative bleeding following cardiac surgeries is still an issue that deranges the medical resources and cost. The oral and injection administrations of blood coagulation protein, Factor VII (FVII), is effective to stop the bleeding. However, its short half-life has limited the effectiveness of this treatment and frequent FVII intake may distress the patients. Instead, incorporating FVII into synthetic biodegradable polymers such as polycaprolactone (PCL) that is commonly used in drug delivery applications should provide a solution. Therefore, this study aimed to immobilize FVII on PCL membranes through a cross-linkage polydopamine (PDA) grafting as an intermediate layer. These membranes are intended to provide a solution for cardiac bleeding in coagulating blood and sealing the sutured region. The membranes were evaluated in terms of its physio-chemical properties, thermal behavior, FVII release profile and biocompatibility properties. The ATR-FTIR was used to analyze the chemical functionalities of the membranes. Further validation was done with XPS where the appearances of 0.45 ± 0.06% sulfur composition and C-S peak have confirmed the immobilization of FVII on the PCL membranes. The cross-linked FVIIs were viewed in spherical immobilization on the PCL membranes with a size range between 30 and 210 nm. The surface roughness and hydrophilicity of the membranes were enhanced with a slight shift of melting temperature. The PCL-PDA-FVII0.03 and PCL-PDA-FVII0.05 membranes, with wide area of FVII immobilization released approximately only 22% of FVII into the solution within 60 days period and, it is found that the PCL-PDA-FVIIx membranes projected the Higuchi release model with non-Fickian anomalous transport. While the cytotoxic and hemocompatibility analyses showed advance cell viability, identical coagulation time and low hemolysis ratio on the PCL-PDA-FVIIx membranes. The erythrocytes were viewed in polyhedrocyte coagulated structure under SEM visualization. These results validate the biocompatibility of the membranes and its ability to prolong blood coagulation, thus highlighting its potential application as cardiac bleeding sealant.
Burkholderia pseudomallei affecting the central nervous system has been extensively reported in the literature. However, combined central nervous system and peripheral nervous system involvement in melioidosis has never been reported. We report a 66-year-old man with diabetes mellitus who was diagnosed to have central nervous system melioidosis and developed acute flaccid quadriplegia. Nerve conduction studies and anti-ganglioside antibodies were consistent with Guillain-Barre syndrome. This case report highlights the importance to recognise the possibility of Guillain Barre syndrome complicating central nervous system melioidosis and stresses the urgency of early consideration of this complication, as early immunomodulatory therapy may hasten neurological recovery.
Anodised titanium has a long history as a coating structure for implants due to its bioactive and ossified surface, which promotes rapid bone integration. In response to the growing literature on anodised titanium, this article is the first to revisit the evolution of anodised titanium as an implant coating. The review reports the process and mechanisms for the engineering of distinctive anodised titanium structures, the significant factors influencing the mechanisms of its formation, bioactivity, as well as recent pre- and post-surface treatments proposed to improve the performance of anodised titanium. The review then broadens the discussion to include future functional trends of anodised titanium, ranging from the provision of higher surface energy interactions in the design of biocomposite coatings (template stencil interface for mechanical interlock) to techniques for measuring the bone-to-implant contact (BIC), each with their own challenges. Overall, this paper provides up-to-date information on the impacts of the structure and function of anodised titanium as an implant coating in vitro and in/ex vivo tests, as well as the four key future challenges that are important for its clinical translations, namely (i) techniques to enhance the mechanical stability and (ii) testing techniques to measure the mechanical stability of anodised titanium, (iii) real-time/in-situ detection methods for surface reactions, and (iv) cost-effectiveness for anodised titanium and its safety as a bone implant coating.
Additive manufacturing has attracted increasing attention worldwide, especially in the healthcare, biomedical, aerospace, and construction industries. In Malaysia, insufficient acceptance of this technology by local industries has resulted in a call for government and local practitioners to promulgate the development of this technology for various industries, particularly for biomedical products. The current study intends to frame the challenges endured by biomedical industries who use 3D printing technology for their manufacturing processes. Qualitative methods, particularly in-depth interviews, were used to identify the challenges faced by manufacturing firms when producing 3D printed biomedical products. This work was able to identify twelve key challenges when deploying additive manufacturing in biomedical products and these include issues related to binder selection, poor mechanical properties, low-dimensional accuracy, high levels of powder agglomeration, nozzle size, distribution size, limited choice of materials, texture and colour, lifespan of materials, customization of fit and design, layer height, and, lastly, build-failure. Furthermore, there also are six challenges in the management of manufacturing biomedical products using 3D printing technology, and these include staff re-education, product pricing, limited guidelines, cyber-security issues, marketing, and patents and copyright. This study discusses the reality faced by 3D printing players when producing biomedical products in Malaysia, and presents a primary reference for practitioners in other developing countries.
Waste materials from natural sources are important resources for extraction and recovery of valuable compounds. Transformation of these waste materials into valuable materials requires specific techniques and approaches. Hydroxyapatite (HAp) is a biomaterial that can be extracted from natural wastes. HAp has been widely used in biomedical applications owing to its excellent bioactivity, high biocompatibility, and excellent osteoconduction characteristics. Thus, HAp is gaining prominence for applications as orthopaedic implants and dental materials. This review summarizes some of the recent methods for extraction of HAp from natural sources including mammalian, aquatic or marine sources, shell sources, plants and algae, and from mineral sources. The extraction methods used to obtain hydroxyapatite are also described. The effect of extraction process and natural waste source on the critical properties of the HAp such as Ca/P ratio, crystallinity and phase assemblage, particle sizes, and morphology are discussed herein.
The differentiation between a pseudo-pneumoperitoneum and true pneumoperitoneum on an initial chest radiograph is challenging but essential to clinical practice. The former is managed conservatively whereas the latter may require surgical intervention. Chilaiditi's sign describes a rare incidental radiological finding of gas filled bowel interpositioned between the right hemi-diaphragm and the liver, which is visible on a plain abdominal or chest radiograph. It is often misdiagnosed as a pneumoperitoneum. Correct diagnosis of Chilaiditi's sign in an asymptomatic patient can prevent unnecessary procedures. We have reported one incidental chest radiograph with Chilaiditi's sign in a patient presenting and treated for pneumonia. The report aims to illustrate the diagnostic dilemma experienced by clinicians in distinguishing a true versus pseudo-pneumoperitoneum on a chest radiograph.
The pharmacokinetics of sublingual artemether (ArTiMist) was investigated in two open-label studies. In study 1, 16 healthy males were randomized to each of four single-dose treatments administered in random order: (i) 15.0 mg of sublingual artemether (5 × 3.0 actuations), (ii) 30.0 mg of sublingual artemether (10 × 3.0 mg), (iii) 30.0 mg of sublingual artemether (5 × 6.0 mg), and (iv) 30.0 mg of artemether in tablet form. In study 2, 16 healthy males were randomized to eight 30.0-mg doses of sublingual artemether given over 5 days as either 10 3.0-mg or 5 6.0-mg actuations. Frequent blood samples were drawn postdose. Plasma artemether and dihydroartemisinin levels were measured using liquid chromatography-mass spectrometry. Population compartmental pharmacokinetic models were developed. In study 1, sublingual artemether absorption was biphasic, with both rate constants being greater than that of the artemether tablets (1.46 and 1.66 versus 0.43/h, respectively). Relative to the tablets, sublingual artemether had greater bioavailability (≥1.24), with the greatest relative bioavailability occurring in the 30.0-mg dose groups (≥1.58). In study 2, there was evidence that the first absorption phase accounted for between 32% and 69% of the total dose and avoided first-pass (FP) metabolism, with an increase in FP metabolism occurring in later versus earlier doses but with no difference in bioavailability between the dose actuations. Sublingual artemether is more rapidly and completely absorbed than are equivalent doses of artemether tablets in healthy adults. Its disposition appears to be complex, with two absorption phases, the first representing pregastrointestinal absorption, as well as dose-dependent bioavailability and autoinduction of metabolism with multiple dosing.
The pharmacokinetics of sublingual artemether (ArTiMist) was investigated in 91 young African children with severe malaria or who could not tolerate oral antimalarial therapy. Each received 3.0 mg/kg of body weight of artemether at 0, 8, 24, 36, 48, and 60 h or until the initiation of oral treatment. Few blood samples were drawn postdose. Plasma artemether and dihydroartemisinin (DHA) levels were measured using liquid chromatography-mass spectrometry, and the data were analyzed using established population compartmental pharmacokinetic models. Parasite clearance was prompt (median parasite clearance time, 24 h), and there were no serious adverse events. Consistent with studies in healthy adults (S. Salman, D. Bendel, T. C. Lee, D. Templeton, and T. M. E. Davis, Antimicrob Agents Chemother 59:3197-3207, 2015, http://dx.doi.org/10.1128/AAC.05013-14), the absorption of sublingual artemether was biphasic, and multiple dosing was associated with the autoinduction of the metabolism of artemether to DHA (which itself has potent antimalarial activity). In contrast to studies using healthy volunteers, pharmacokinetic modeling indicated that the first absorption phase did not avoid first-pass metabolism, suggesting that the drug is transferred to the upper intestine through postdose fluid/food intake. Simulations using the present data and those from an earlier study in older Melanesian children with uncomplicated malaria treated with artemether-lumefantrine tablets suggested that the bioavailability of sublingual artemether was at least equivalent to that after conventional oral artemether-lumefantrine (median [interquartile range] areas under the concentration-time curve for artemether, 3,403 [2,471 to 4,771] versus 3,063 [2,358 to 4,514] μg · h/liter, respectively; and for DHA, 2,958 [2,146 to 4,278] versus 2,839 [1,812 to 3,488] μg · h/liter, respectively; P ≥ 0.42). These findings suggest that sublingual artemether could be used as prereferral treatment for sick children before transfer for definitive management of severe or moderately severe malaria.
AIM: Chronic venous ulcers usually occur as an occupational hazard due to venous insufficiency with venous hypertension. Endovenous laser treatment (EVT) is used to treat varicose veins with venous ulcers and outcome including demography assessed in the different races.
PROCEDURE: 145 lower limbs(right 39.3%, left 60.7%) with venous ulcers involving reflux of the great saphenous (132 cases) and / or small saphenous (57 cases) veins underwent EVT with 980 nm diode laser for single (123 cases) or both (11 cases) legs intervention. Supplementary procedures required multiple avulsions and / or sclerotherapy. Holistic advice of multilayered bandaging, graduated compression stockings, weight reduction and lifestyle changes enforced.
RESULT: The average age with venous ulcers was 53.6 years.The mean BMI was 26.8 : the Chinese, Indian and Malay BMIs were 25.1, 28.1 and 31.3 respectively. Symptoms that included pain, swelling, heaviness and cramps assessed pre- and postsurgically were significantly reduced (<0.0001), using the Wilcoxan signed rank test. Of the occupations involved by race, the Chinese were mostly salespersons, Indians blue collar workers and Malays foodrelated workers. Young overweight Indians with sedentary occupations were most predisposed to venous ulcers. Gram negative organisms 63.4% and gram positive organisms 36.6% were isolated in the ulcers. Most ulcers 63.5% measured <2 cm and majority 73.8% localised in the gaiter area.
DISCUSSION: Results of EVT in healing ulcers with no recurrences more than 2 years were successful in 89.7% (130/145). Complications included numbness foot 7.5% and DVT 1.4%. 10.3% (15 cases) had recurrence of venous ulcers within 2 years. In terms of satisfaction 32.3% experienced as very satisfied while 63.4% were satisfied and 4.3% unsatisfied. In conclusion EVT is a useful adjunct with with minimal invasion in managing venous ulcers holistically.
Metformin is contraindicated in patients with renal impairment; however, there is poor adherence to current dosing guidelines. In addition, the pharmacokinetics of metformin in patients with significant renal impairment are not well described. The aims of this study were to investigate factors influencing the pharmacokinetic variability, including variant transporters, between healthy subjects and patients with type 2 diabetes mellitus (T2DM) and to simulate doses of metformin at varying stages of renal function.
The present study determined the pharmacokinetic profile of vancomycin in premature Malaysian infants. A one-compartment infusion model with first-order elimination was fitted to serum vancomycin concentration data (n = 835 points) obtained retrospectively from the drug monitoring records of 116 premature newborn infants. Vancomycin concentrations were estimated by a fluorescence polarization immunoassay. Population and individual estimates of clearance and distribution volume and the factors which affected the variability observed for the values of these parameters were obtained using a population pharmacokinetic modeling approach. The predictive performance of the population model was evaluated by visual inspections of diagnostic plots and nonparametric bootstrapping with replacement. Dosing guidelines targeting a value of > or =400 for the area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC(24)/MIC ratio) were explored using Monte Carlo simulation. Body size (weight), postmenstrual age, and small-for-gestational-age status are important factors explaining the between-subject variability of vancomycin pharmacokinetic parameter values for premature neonates. The typical population parameter estimates of clearance and distribution volume for a 1-kg premature appropriate-for-gestational-age neonate with a postmenstrual age of 30 weeks were 0.0426 liters/h and 0.523 liters, respectively. There was a 20% reduction in clearance for small-for-gestational-age infants compared to the level for the appropriate-for-gestational-age control. Dosage regimens based on a priori target response values were formulated. In conclusion, the pharmacokinetic parameter values for vancomycin in premature Malaysian neonates were estimated. Improved dosage regimens based on a priori target response values were formulated by incorporating body size, postmenstrual age, and small-for-gestational-age status, using Monte Carlo simulations with the model-estimated pharmacokinetic parameter values.
This study was carried out to compare the rate and extent of absorption of a generic salbutamol in oral dosage form (Brethmol, 4 mg) with the proprietary equivalent product (Ventolin, 4 mg), in healthy adult subjects, under fasting conditions. The study was a single dose, randomized, two way crossover study with a four-week washout period. It involved 22 healthy volunteers who received a single dose (4 mg) of the test and the reference products after an overnight fast of at least 10 hours. Blood samples were collected at pre-dose and a serial of 14 samples were collected from each of the subject from 1 h until 48 h post-dose. Plasma concentrations of salbutamol were analyzed using GCMS method. The mean AUC(0-yen) values were 91.26 and 96.45 h.ng/ml for reference and test product, respectively. The mean C(max) values were 12.26 and 12.38 ng/ml and the mean t(max) values were 2.80 and 2.33 hours for reference and test product, respectively. Analysis of variance showed that the 90% confidence intervals on the relative difference of the ratio for the AUC(0-yen) and the C(max) for the test and reference products were contained within the bioequivalence limit (80 - 125%) (C(max): 89.8 - 110.5% and AUC(0-yen): 91.6 - 121.5%). There was no statistically significant difference for the t(max) between the test and reference formulations (p = 0.30). The test formulation was found to be bioequivalent to the reference formulation with regard to AUC(0-yen) and C(max). There was no statistically significant difference in Brethmol and Ventolin t(max). In conclusion, Brethmol and Ventolin are bioequivalent in healthy subjects.
Newcastle disease virus (NDV) strains can be classified as virulent or avirulent based upon the severity of the disease. Differentiation of the virus into virulent and avirulent is necessary for effective control of the disease. Biopanning experiments were performed using a disulfide constrained phage displayed heptapeptide library against three pathotypes of NDV strains: velogenic (highly virulent), mesogenic (moderately virulent) and lentogenic (avirulent). A phage clone bearing the peptide sequence SWGEYDM capable of distinguishing virulent from avirulent NDV strains was isolated. This phage clone was employed as a diagnostic reagent in a dot blot assay and it successfully detected only virulent NDV strains.
Impaired S-mephenytoin 4'-hydroxylation is a well-described genetic polymorphism affecting drug metabolism in humans. Although ethnic differences in its distribution of polymorphism has been described, it is not known whether there is an ethnic heterogeneity of the structure and expression of the CYP2C19 enzyme in the Malaysian population.
AIMS: Nafcillin (Wyeth Laboratories, Philadelphia, PA, USA) has been reported to induce the metabolism of cyclosporin and warfarin, which are known substrates of cytochrome P-450 (CYP). However, there has not been any report to date on its possible interaction with nifedipine, an index substrate of the enzyme, CYP3A4.
METHODS: Nine healthy normotensive subjects participated in this randomized placebo-controlled two-way crossover study examining the effects of 5 days' pretreatment of nafcillin 500 mg or placebo four times daily on the pharmacokinetics of an oral dose of nifedipine 10 mg. Plasma nifedipine concentrations were measured by gas chromatography-mass spectro.
RESULTS: The area under the plasma nifedipine concentration-time curve (AUC0-alpha) in nafcillin-pretreated subjects (80.9 +/- 32.9 micro g l-1 h-1) was significantly decreased compared with subjects who received only nifedipine (216.4 +/- 93.2 micro g l-1 h-1) (P < 0.001). Total plasma clearance of nifedipine (CL/F) was significantly increased with nafcillin pretreatment (138.5 +/- 42.0 l h-1 vs 56.5 +/- 32.0 l h-1) (P < 0.002).
CONCLUSIONS: The results show that nafcillin pretreatment markedly increased the clearance of nifedipine and suggest that nafcillin is a potent inducer of CYP enzyme.
OBJECTIVE: The aim of this study was to investigate the prevalence of skin prick test (SPT) reactivity to common aeroallergens among Malaysian asthmatic patients with and without rhinitis.
METHODOLOGY: An SPT using eight aeroallergens (Dermatophagoides pteronyssinus, Dermatophagoides farinae, cat fur, cockroach, Acacia sp., Bermuda grass, Aspergillus fumigatus and Aspergillus niger) was performed on 206 asthmatic patients.
RESULTS: One hundred and forty patients (68%) were reactive to at least one of the aeroallergens. Among the SPT-positive patients, a positive prick test reaction to the house dust mites, D. pteronyssinus (93.6%), and D. farinae (81.4%) was most common, followed by cat fur (20.0%), cockroach (7.9%), Bermuda grass (7.9%), Acacia sp. (7.9%), A. fumigatus (0.7%) and A. niger (0.7%). A history of rhinitis was elicited in 111 (53.9%) patients and 95 (85.3%) of these patients were SPT-positive compared with only 45 (47.4%) of 95 patients with asthma symptoms alone (P < 0.001). The presence of rhinitis and a young age of onset of asthma were independent factors for positive SPT reaction to at least one of the aeroallergens.
CONCLUSIONS: The prevalence of SPT reactivity to common aeroallergens is high among Malaysian asthmatics, particularly in those with an early age of onset and in those with coexisting rhinitis.
Study site: Asthma Clinic, University of Malaya Medical Centre, Kuala Lumpur, Malaysia
To determine the occupational risk of Mycobacterium tuberculosis infection among healthcare workers (HCWs) and to examine the utility of tuberculin skin testing in a developing country with a high prevalence of bacille Calmette-Guerin vaccination.