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Fulltext Routine coagulation tests in cases of missed abortion--is it really necessary?

Chandran R, Adeeb N

Med J Malaysia, 1992 Dec;47(4):287-9.
PMID: 1303481

Many gynaecological units have a policy of performing routine coagulation tests in cases of missed abortion. For many years now, it has been accepted practice in our unit to perform routinely a platelet count, bleeding time (BT), clotting time (CT) and plasma fibrinogen (P. fib) level prior to evacuation in cases of missed abortion. We are not sure how or why these 4 tests came to be chosen as a coagulation 'screen'. As they are not totally adequate in detecting disseminated intravascular coagulation (DIC), we wondered if these tests added to the management in any way.
Composite mucinous and granulosa-theca-cell tumour of the ovary: an unusual neoplasm

Chandran R, Rahman H, Gebbie D

Aust N Z J Obstet Gynaecol, 1993 Nov;33(4):437-9.
PMID: 8179566

This case represents a unique primary ovarian tumour consisting of malignant mucinous elements and granulosa-theca-cell elements, the histogenesis of which remains uncertain. It also underscores the need for thorough sampling of mucinous tumours in order to discover a possible coexisting, different neoplastic component.
Fulltext Bilateral pure gonadoblastoma in a 46 XY individual--a case report

Siti Aishah MA, Chandran R, Tahir H

Med J Malaysia, 1991 Dec;46(4):384-7.
PMID: 1840451

We report here a rare case of bilateral pure gonadoblastoma which accounts for only 0.2% of all ovarian tumours seen at Universiti Kebangsaan Malaysia from 1980 to 1987. This tumour occurred in an 18 year old Chinese "female" who presented with primary amenorrhoea. Examination showed a phenotypic female with poorly developed external gentalia. Exploratory laparotomy revealed a hypoplastic uterus, rudimentary fallopian tubes and streak gonads. Histological examination of the gonads showed a mixed tumour comprising large germ cells and smaller sex cord derivatives arranged in characteristic nests or islands containing hyaline material.
Fulltext Perforating invasive mole masquerading as an ovarian tumour--case report

Chandran R, Tham KY, Rose I

Med J Malaysia, 1991 Sep;46(3):255-8.
PMID: 1839922

An invasive mole causing uterine perforation is a rare occurrence. We describe below a case with an unusual presentation which was mistaken for an ovarian tumour. The difficulty in diagnosis and the need for a high index of suspicion is highlighted.
Fetal cerebral Doppler in the recognition of fetal compromise

Chandran R, Serra-Serra V, Sellers SM, Redman CW

Br J Obstet Gynaecol, 1993 Feb;100(2):139-44.
PMID: 8476805

OBJECTIVE: To establish reference ranges for the human fetal middle cerebral artery pulsatility index (MCA PI) for the local obstetric population, and to compare computerised antenatal fetal heart rate (FHR) analysis with the MCA PI as indicators of fetal compromise.
DESIGN: Prospective data collection for selected patients.
SETTING: High risk pregnancy unit of a teaching hospital.
SUBJECTS: Group 1 consisted of 18 healthy women with uncomplicated singleton pregnancies. Group 2 consisted of 27 women admitted to the high risk pregnancy unit over a 9 month period with intrauterine growth retardation and other related problems; all these women were delivered by prelabour caesarean section.
INTERVENTION: Serial Duplex sonography to determine fetal MCA PI in Groups 1 and 2. Serial FHR analysis using computerised numerical techniques in Group 2 only.
MAIN OUTCOME MEASURES: Serial MCA PI values from 24 to 39 completed weeks of gestation in Group 1. Comparison of serial MCA PI values with FHR analysis in relation to fetal outcome in Group 2.
RESULTS: In Group 1 the MCA PI diminished significantly as gestation advanced from 1.73 (SD 0.25) at 24 weeks to 1.38 (SD 0.26) at 39 weeks (P < 0.01). In Group 2 eleven babies were hypoxaemic at delivery: all had low MCA PI values while only nine had an abnormal FHR prior to delivery.
CONCLUSION: In normal pregnancy, there is a fall in the fetal MCA PI with advancing gestation which probably reflects a decreasing vascular resistance to fetal cerebral blood flow. Hypoxaemia at delivery appeared to be better recognised by the fetal MCA flow velocity waveform than the FHR analysis. This increased sensitivity, however, was achieved at the expense of a reduced specificity. Larger studies are needed to confirm the findings of this preliminary investigation.
Fulltext First trimester prenatal diagnosis of beta-thalassaemia following chorionic villus sampling

Chandran R, Ainoon O, Anson I, Anne J, Cheong SK

Med J Malaysia, 1993 Sep;48(3):341-4.
PMID: 8183149

DNA analysis for the diagnosis of beta-thalassaemia is a relatively new technique in Malaysia. This, combined with chorionic villus sampling, has enabled us to offer prenatal diagnosis in the first trimester for this common condition. To the best of our knowledge, this has not hitherto been reported in Malaysia.
An effective strategy for unit commitment of microgrid power systems integrated with renewable energy sources including effects of battery degradation and uncertainties

Manoharan P, Chandrasekaran K, Chandran R, Ravichandran S, Mohammad S, Jangir P

Environ Sci Pollut Res Int, 2024 Feb;31(7):11037-11080.
PMID: 38217814 DOI: 10.1007/s11356-023-31608-z

The large use of renewable sources and plug-in electric vehicles (PEVs) would play a critical part in achieving a low-carbon energy source and reducing greenhouse gas emissions, which are the primary cause of global warming. On the other hand, predicting the instability and intermittent nature of wind and solar power output poses significant challenges. To reduce the unpredictable and random nature of renewable microgrids (MGs) and additional unreliable energy sources, a battery energy storage system (BESS) is connected to an MG system. The uncoordinated charging of PEVs offers further hurdles to the unit commitment (UC) required in contemporary MG management. The UC problem is an exceptionally difficult optimization problem due to the mixed-integer structure, large scale, and nonlinearity. It is further complicated by the multiple uncertainties associated with renewable sources, PEV charging and discharging, and electricity market pricing, in addition to the BESS degradation factor. Therefore, in this study, a new variant of mixed-integer particle swarm optimizer is introduced as a reliable optimization framework to handle the UC problem. This study considers six various case studies of UC problems, including uncertainties and battery degradation to validate the reliability and robustness of the proposed algorithm. Out of which, two case studies defined as a multiobjective problem, and it has been transformed into a single-objective model using different weight factors. The simulation findings demonstrate that the proposed approach and improved methodology for the UC problem are effective than its peers. Based on the average results, the economic consequences of numerous scenarios are thoroughly examined and contrasted, and some significant conclusions are presented.
Investigation and Optimization of Hydrogel Microneedles for Transdermal Delivery of Caffeine

Chandran R, Mohd Tohit ER, Stanslas J, Salim N, Tuan Mahmood TM

Tissue Eng Part C Methods, 2022 10;28(10):545-556.
PMID: 35485888 DOI: 10.1089/ten.TEC.2022.0045

Caffeine is therapeutically effective for treating apnea, cellulite formation, and pain management. It also exhibits neuroprotective and antioxidant activities in different models of Parkinson's disease and Alzheimer's disease. However, caffeine administration in a minimally invasive and sustainable manner through the transdermal route is challenging owing to its hydrophilic nature. Therefore, this study demonstrated a transdermal delivery approach for caffeine by utilizing hydrogel microneedle (MN) as a permeation enhancer. The influence of formulation parameters such as molecular weight (MW) of PMVE/MA (polymethyl vinyl ether/maleic anhydride) copolymer and sodium bicarbonate (NaHCO3) concentration on the swelling kinetics and mechanical integrity of the hydrogel MNs was investigated. In addition, the effect of different MN application methods and needle densities of hydrogel MN on the skin insertion efficiency and penetration depth was also evaluated. The swelling degree at equilibrium percentage (% Seq) recorded for hydrogels fabricated with Gantrez S-97 (MW = 1,500,000 Da) was significantly higher than formulation with Gantrez AN-139 (MW = 1,080,000 Da). Increasing the concentration of NaHCO3 also significantly increased the % Seq. Moreover, a 100% penetration was recorded for both the applicator and combination of applicator and thumb pressure compared with only 11% for thumb pressure alone. The average diameter of micropores created by the applicator method was 62.94 μm, which was significantly lower than the combination of both applicator and thumb pressure MN application (100.53 μm). Based on histological imaging, the penetration depth of hydrogel MN increased as the MN density per array decreased. The hydrogel MN with the optimized formulation and skin insertion parameters was tested for caffeine delivery in an in vitro Franz diffusion cell setup. Approximately 2.9 mg of caffeine was delivered within 24 h, and the drug release profile was best fitted to the Korsmeyer-Peppas model, displaying Super Case II kinetics. In conclusion, a combination of thumb and impact application methods and reduced needle density improved the skin penetration efficiency of hydrogel MNs. The results also show that hydrogel MNs fabricated from 3% w/w NaHCO3 and high MW of copolymer exhibit optimum physical and swelling properties for enhanced transdermal delivery.
Molecular defects in the beta-globin gene identified in different ethnic groups/populations during prenatal diagnosis for beta-thalassemia: a Malaysian experience

Tan JA, George E, Tan KL, Chow T, Tan PC, Hassan J, et al.

Clin Exp Med, 2004 Dec;4(3):142-7.
PMID: 15599663 DOI: 10.1007/s10238-004-0048-x

Beta-thalassemia is the most-common genetic disorder of hemoglobin synthesis in Malaysia, and about 4.5% of the population are heterozygous carriers of the disorder. Prenatal diagnosis was performed for 96 couples using the Amplification Refractory Mutation System and Gap-Polymerase Chain Reaction. We identified 17 beta-globin defects-initiation codon for translation (T-G), -29 (A-G), -28 (A-G), CAP +1 (A-C), CD 8/9 (+G), CD 15 (G-A), CD 17 (A-T), CD 19 (A-G), Hb E (G-A), IVS1-1 (G-T), IVS1-5 (G-C), CD 41/42 (-CTTT), CD 71-72 (+A), IVS2-654 (CT), poly A(A-G), 100-kb Ggamma(Agammadeltabeta) degrees and 45-kb Filipino deletions. The 192 beta-alleles studied comprised Chinese (151 patients), Malay (21), Orang Asli from East Malaysia (15), Filipino (1), Indian (1), Indonesian Chinese (2), and Thai (1). In the Chinese, 2 beta-globin defects at CD 41/42 and IVS2-654 were responsible for 74% of beta-thalassemia. beta-mutations at CD 19, IVS1-1 (G-T), IVS1-5, poly A, and hemoglobin E caused 76% of the hemoglobin disorders in the Malays. The Filipino 45-kb deletion caused 73.3% of bthalassemia in the Orang Asli. Using genomic sequencing, the rare Chinese beta-mutation at CD 43 (G-T) was confirmed in 2 Chinese, and the Mediterranean mutation IVS1-1 (G-A) was observed in a Malay beta-thalassemia carrier. The beta-globin mutations confirmed in this prenatal diagnosis study were heterogenous and 65 (68%) couples showed a different globin defect from each other. The use of specific molecular protocols has allowed rapid and successful prenatal diagnosis of beta-thalassemia in Malaysia.
Shifting Paradigms and Arising Concerns in Severe Hemophilia A Treatment

Chandran R, Tohit ERM, Stanslas J, Salim N, Mahmood TMT, Rajagopal M

Semin Thromb Hemost, 2024 Jan 15.
PMID: 38224699 DOI: 10.1055/s-0043-1778103

The management of hemophilia A has undergone a remarkable revolution, in line with technological advancement. In the recent past, the primary concern associated with Factor VIII (FVIII) concentrates was the risk of infections, which is now almost resolved by advanced blood screening and viral inactivation methods. Improving patients' compliance with prophylaxis has become a key focus, as it can lead to improved health outcomes and reduced health care costs in the long term. Recent bioengineering research is directed toward prolonging the recombinant FVIII (rFVIII) coagulant activity and synthesising higher FVIII yields. As an outcome, B-domain deleted, polyethylene glycolated, single-chain, Fc-fused rFVIII, and rFVIIIFc-von Willebrand Factor-XTEN are available for patients. Moreover, emicizumab, a bispecific antibody, is commercially available, whereas fitusiran and tissue factor pathway inhibitor are in clinical trial stages as alternative strategies for patients with inhibitors. With these advancements, noninfectious complications, such as inhibitor development, allergic reactions, and thrombosis, are emerging concerns requiring careful management. In addition, the recent approval of gene therapy is a major milestone toward a permanent cure for hemophilia A. The vast array of treatment options at our disposal today empowers patients and providers alike, to tailor therapeutic regimens to the unique needs of each individual. Despite significant progress in modern treatment options, these highly effective therapies are markedly more expensive than conventional replacement therapy, limiting their access for patients in developing countries.
Drug-Loaded Hydrogel Microneedles for Sustainable Transdermal Delivery of Macromolecular Proteins

Chandran R, Mohd Tohit ER, Stanslas J, Salim N, Tuan Mahmood TM

Curr Drug Deliv, 2025 Jan 15.
PMID: 39819406 DOI: 10.2174/0115672018346286241121052105

INTRODUCTION: Poly(methyl vinyl ether co-maleic acid) (PMVE/MA) hydrogel microneedles (HMN) are investigated for transdermal delivery of macromolecular drugs owing to their biocompatibility and super-swelling properties. However, the drug delivery efficacy reduces with increasing molecular weight due to the entrapment within the HMN matrices. Furthermore, integrating external drug reservoirs extends the drug diffusion path and reduces the efficiency of drug permeation.
METHODS: A direct drug loading approach in the HMN matrix was introduced in this work following a pH modification step. The effect of pH modification on the physicochemical properties of HMN was studied. Then, bovine serum albumin (BSA), a model protein, was loaded into the pH-modified HMN, and the morphological changes in HMN and protein stability were also assessed. Finally, the efficacy of BSA-loaded HMN in the transdermal delivery was evaluated ex vivo.
RESULTS: A significant increase in swelling was recorded following the pH modification of HMN (p < 0.001). The structure of pH-modified hydrogel was highly porous, and ATR-FTIR spectra indicated a shift in the carboxylic peak. The secondary structure of BSA loaded in the pH-modified HMN was also preserved. The BSA-loaded HMN mediated a sustained ex-vivo drug release with a cumulative release of 64.70% (3.88 mg) in 24 h.
CONCLUSION: Hence, the model drug-incorporated PMVE/MA HMN system shows potential for sustainable transdermal delivery of proteins.