Clinical characteristic and management of haemophilia patients in Malaysia: A single centre experience.

INTRODUCTION: Haemophilia is one of the commonest inherited bleeding disorders which may lead to long term disabilities if not treated properly. Our aim of study is to understand the clinical characteristic, treatment and complications of adult haemophilia patients in our centre. MATERIALS AND METHODS: A retrospective cross-sectional review of all adult haemophilia A (HA) or haemophilia B (HB) patients who received treatment in Hospital Pulau Pinang from January 2021 to December 2022 was conducted. Data was retrieved from patients' medical records. RESULTS: A total of 75 haemophilia patients (64 HA and 11 HB) were included in this study with median age of 37 years (range 19 70). 42 of them had severe haemophilia (50% of HA, 91% of HB). All HB and 93.8% of severe HA patients were on prophylaxis. Six severe and one mild HA patients developed inhibitor with four of them currently on non-factor prophylaxis. 24 patients (32%) had prior hepatitis C infection and all of them have been successfully treated. The mean annual bleeding rate for severe haemophilia patients were 1.77 (SD ±3.6). Target joints were observed in 9.3% of patients with ankle joint (71.4%) being the most affected joint. More than one quarter (26.7%) of our patients have comorbidities with majority of them having hypertension (17/20), followed by diabetes mellitus (5/20) and ischemic heart disease (5/20). CONCLUSION: Our study showed that a significant number of adult patients with haemophilia have comorbidities. Apart from optimising factor replacement therapy, future planning should include improvement in screening, risk modification and prevention of cardiovascular disease.

Gait improvement by high-frequency stimulation of the subthalamic nucleus in Parkinsonian mice is not associated with changes of the cholinergic system in the pedunculopontine nucleus.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is standard care for severe motor symptoms of Parkinson's disease (PD). However, a challenge of DBS remains improving gait. Gait has been associated with the cholinergic system in the pedunculopontine nucleus (PPN). In this study, we investigated the effects of long-term intermittent bilateral STN-DBS on PPN cholinergic neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) Parkinsonian mouse model. Motor behavior, previously assessed by the automated Catwalk gait analysis, demonstrated a parkinsonian-like motor phenotype with static and dynamic gait impairments, which were reversed by STN-DBS. In this study, a subset of brains was further immunohistochemically processed for choline acetyltransferase (ChAT) and the neuronal activation marker c-Fos. MPTP treatment resulted in a significant reduction of PPN ChAT expressing neurons compared to saline treatment. STN-DBS did not alter the number of ChAT expressing neurons, nor the number of double-labelled PPN neurons for ChAT and c-Fos. Although STN-DBS improved gait in our model this was not associated with an altered expression or activation of PPN acetylcholine neurons. Motor and gait effects of STN-DBS are therefore less likely to be mediated by the STN-PPN connection and PPN cholinergic system.

Matrix Matters: Assessment of Commutability among BK Virus Assays and Standards.

Quantitative testing of BK virus (BKPyV) nucleic acid has become the standard of care in transplant patients. While the relationship between interassay harmonization and commutability has been well characterized for other transplant-related viruses, it has been less well studied for BKPyV, particularly regarding differences in commutability between matrices. Here, interassay agreement was evaluated among six real-time nucleic acid amplification tests (NAATs) and one digital PCR (dPCR) BKPyV assay. Differences in the commutability of three quantitative standards was examined across all assays using a variety of statistical approaches. Panels, including 40 samples each of plasma and urine samples previously positive for BKPyV, together with one previously negative plasma sample and four previously negative urine samples, were tested using all assays, with each real-time NAAT utilizing its usual quantitative calibrators. Serial dilutions of WHO, National Institute for Standards and Technology (NIST), and commercially produced (Exact/Bio-Rad) reference materials were also run by each assay as unknowns. The agreement of the clinical sample values was assessed as a group and in a pairwise manner. The commutability was estimated using both relativistic and quantitative means. The quantitative agreement across assays in the urine samples was within a single log10 unit across all assays, while the results from the plasma samples varied by 2 to 3 log10 IU/mL. The commutability showed a similar disparity between the matrices. Recalibration using international standards diminished the resulting discrepancies in some but not all cases. Differences in the sample matrix can affect the commutability and interassay agreement of quantitative BKPyV assays. Differences in commutability between matrices may largely be due to factors other than those such as amplicon size, previously described as important in the case of cytomegalovirus. Continued efforts to standardize viral load measurements must address multiple sources of variability and account for differences in assay systems, quantitative standards, and sample matrices.

Three-dimensional pharyngeal airway changes in dento-skeletal class II patients after two-jaw orthognathic surgery with segmentation - a pilot study.

PURPOSE: To investigate short- and long-term post-surgical three-dimensional changes of pharyngeal airway morphology and hyoid bone position in dento-skeletal class II deformity patients after two-jaw surgery with segmentation. METHODS: Relations between skeletal movement, hyoid bone position and three-dimensional pharyngeal airway changes were retrospectively analyzed on pre- and post-surgical CBCTs in dento-skeletal class II patients who underwent orthognathic two-jaw surgery with segmentation. RESULTS: While long-term significant reductions in length (P= 0.003), surface area (P= 0.042) and volume (P= 0.004) were found in the nasopharynx, the highly significant increases in oropharyngeal airway length, surface area, volume and the minimal cross-sectional area (P < 0.05) prevailed only in the short-term. Although a significant antero-superior movement of the hyoid bone was detected both in short- and long-term follow-up CBCTs (P < 0.05), only its superior, but not the anterior movement was found to be associated with an increased lateral width of the oropharyngeal minimal cross-sectional area. CONCLUSION: Two-jaw orthognathic surgery with segmentations in dento-skeletal class II patients improved oropharyngeal airway parameters significantly in the short-, but not long-term.

Carotid intima media thickness and high sensitivity C-reactive protein as markers of cardiovascular risk in a malaysian population.

INTRODUCTION: Carotid intima media thickness (CIMT) being a cost effective and easily performed technique is useful in the detection of subclinical atherosclerosis and has been shown to be a prognosticator of cardiovascular events. The primary objective of this study was to obtain the distribution of CIMT measurements, highly sensitive C reactive protein (hs-CRP) and assessing health awareness and attitudes of the Malaysian population at cardiovascular disease (CVD) risk and not receiving lipid lowering agents. Secondarily the study sought to assess the significance of the relationship between these measurements against various patient characteristics. METHODS: Measurements of CIMT are obtained by ultrasonography of 12 sites within the common carotid artery was recorded for 123 subjects from a single centre tertiary hospital of Malaysia who had two or more CVD risk factors but were not receiving lipid lowering therapy. CVD risk factors and lipid and glucose profiles were analyzed with respect to distribution of CIMT and high-sensitivity Creactive protein (hs-CRP) values. RESULTS: The mean-max CIMT was 0.916±0.129mm (minimum 0.630mm, maximum 1.28mm) and the mean-mean CIMT was 0.743±0.110mm (minimum 0.482mm, maximum 1.050mm) and mean hs-CRP was 0.191mg/dL (minimum 0.030mg/dL, maximum 5.440mg/dL). Multivariate analyses confirmed a significant association between increasing CIMT and increasing age, total and low density lipoprotein cholesterol while log-transformed hs-CRP levels showed significant association with increasing body mass index, waist circumference, high blood glucose and triglyceride levels. Our patients had good health awareness on CVD. CONCLUSION: Newly defined CIMT measurements and hs-CRP levels may be useful adjunctive tools to screen for atherosclerosis in the Malaysian population. It may help in refining risk stratification on top of traditional clinical assessment.

Emergency stenting of vertical vein in a neonate with obstructed supracardiac total anomalous pulmonary venous drainage.

A late preterm newborn baby presented with respiratory distress and increasing cyanosis within 2 hours of birth. Bedside transthroracic echocardiography showed a critically obstructed vertical vein in a supracardiac total anomalous pulmonary venous drainage (TAPVd). Emergency stenting of the vertical vein was successfully performed at 24 hours of life.

Building pharmacogenetics into a pharmacovigilance program in Singapore: using serious skin rash as a pilot study.

To study the possible genetic associations with adverse drug reactions (ADR), the Singapore Health Sciences Authority (HSA) has piloted a program to collect DNA and phenotype data of ADR cases as part of its pharmacovigilance program. Between 2009 and 2012, HSA screened 158 cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). To assess the association between HLA-B*1502 and carbamazepine (CBZ)-induced SJS/TEN, 13 cases and 26 drug-tolerant controls were analyzed. All 13 CBZ-SJS/TEN cases and 3/26 controls were HLA-B*1502 positive (odds ratio 181, 95% confidence interval: 8.7-3785, P=6.9 × 10(-8)). Discussions of the finding with the Ministry of Health and an expert panel led to the decision to make HLA-B*1502 testing the standard of care prior to first use of CBZ in Asians and to subsidize the genotyping test at public hospitals. This program illustrates the role of a regulatory authority in advancing the use of pharmacogenetics for drug safety.

Are postoperative intravenous antibiotics necessary after bimaxillary orthognathic surgery? A prospective, randomized, double-blind, placebo-controlled clinical trial.

Postoperative antibiotic prophylaxis is often administered intravenously, despite an increased morbidity rate compared with oral application. This study investigates whether a postoperative oral antibiotic regimen is as effective as incorporation of intravenous antibiotics after bimaxillary orthognathic surgery. 42 patients who underwent bimaxillary orthognathic surgery between December 2008 and May 2010 were randomly allocated to 2 placebo-controlled postoperative antibiotic prophylaxis groups. Group 1 received oral amoxicillin 500mg three times daily; group 2 received intravenous ampicillin 1g four times daily, during the first two postoperative days. Both groups subsequently took oral amoxicillin for three more days. Clinically, the infection rate was assessed in both study groups for a period of 6 weeks after the surgery. 9 patients (21.4%) developed infection. No adverse drug event was detected. No significant difference (p=0.45) was detected in the infection rate between group 1 (3/21) and group 2 (6/21). Age, type of surgical procedures, duration of the operative procedure, surgical procedure-related events, blood loss, and blood transfusion were all found not related to infection (p>0.05). Administration of more cost-effective oral antibiotic prophylaxis, which causes less comorbidity, can be considered to be safe in bimaxillary orthognathic surgery with segmentalizations.

High-frequency stimulation of the subthalamic nucleus inhibits the firing of juxtacellular labelled 5-HT-containing neurones.

High-frequency stimulation (HFS) of the subthalamic nucleus (STN) is an established neurosurgical therapy for movement disability in advanced Parkinson's disease (PD), but some patients experience psychiatric side-effects like depression. In a previous electrophysiological study, we observed that HFS of the STN inhibited a population of neurones in the rat dorsal raphe nucleus (DRN), with firing properties characteristic of 5-HT neurones. The present study extended these findings to a second population of neurones, and combined extracellular recording with juxtacellular-labelling to investigate the chemical identity of the neurones affected by HFS. Bilateral HFS (130 Hz, 100-200 µA, 5 min) of the STN inhibited (26.0±2.9%) the firing of 37/74 DRN neurones displaying a slow, regular firing pattern. Slower firing neurones were more strongly inhibited than those firing faster. Importantly, 10 inhibited DRN neurones were juxtacellular-labelled with neurobiotin, and all neurones contained 5-HT as shown by post-mortem 5-HT immunocytochemistry. A minority of slow firing DRN neurones (18/74) were activated by STN HFS (37.9±8.3%) which was not observed previously. Of these neurones, three were juxtacellular-labelled and one was 5-HT immunopositive. Also a small number of DRN neurones (19/74) did not respond to HFS, four of which were juxtacellular-labelled and all contained 5-HT. These data show that individual chemically-identified 5-HT-containing neurones in the DRN were modulated by STN HFS, and that the majority were inhibited but some were activated and some failed to respond. These data extend previous findings of modulation of the 5-HT system by STN HFS but suggest a destabilisation of the 5-HT system rather than simple inhibition as indicated previously. Although the mechanism is not yet known, such changes may contribute to the psychiatric side-effects of STN stimulation in some PD patients.

Physical fitness of normal, stunted and overweight children 6-13 years in Oaxaca, Mexico.

BACKGROUND/OBJECTIVE: The objective of this study is to compare the growth and physical fitness of normal, stunted and overweight/obese (owt/ob) Oaxaca children 6-13 years. SUBJECTS/METHODS: This study was a cross-sectional, included 688 school children (grades 1-3, 4-6), aged 6-13 years, from an indigenous rural community (n=361) and colonia popular (n=327) in Oaxaca, southern Mexico. MEASUREMENTS: Anthropometry-weight, height, sitting height, limb circumferences, skinfolds. Derived-body mass index, sitting height/height ratio, leg and step lengths, limb muscle areas, sum of skinfolds. Physical fitness-sit and reach, sit-ups, distance run, grip strength, standing long jump, 35 yard dash. Physical activity-steps to and from school, household chores, sports participation. ANALYSIS: Normal-not stunted, not owt/ob; stunted-not owt/ob; and owt/ob-not stunted were compared with multivariate analysis of covariance controlling for age. Two children were stunted and owt/ob, and were excluded. RESULTS: Age-adjusted means for body size, muscularity, adiposity and grip strength showed a gradient, owt/ob>normal>stunted in both sexes and grade levels (P<0.001). Relative position of stunted and owt/ob children was reversed for strength per unit mass. Stunted and normal children ran a greater distance than owt/ob children (P<0.05). Normal, stunted and owt/ob children did not differ consistently in other fitness items and indicators of activity and inactivity. CONCLUSION: Size, muscularity, fatness and strength differed significantly, owt/ob>normal>stunted, but owt/ob children had less strength per unit mass and poorer endurance. Normal and stunted children did not differ consistently in fitness. Physical activity and television time did not differ among the three groups.

Exogenous ochronosis in ethnic Chinese Asians: a clinicopathological study, diagnosis and treatment.

BACKGROUND: Exogenous ochronosis is believed to be an uncommon complication of treatment with hydroquinone- containing skin-lightning agents. It is widely believed that the condition is found almost exclusively in dark-skinned individuals and uncommon in other skin-types. AIMS: To show that exogenous ochronosis may be present in ethnic Chinese Asians. MATERIALS & METHODS: Facial skin biopsies were obtained from suspicious lesions in ethnic Chinese patients presenting at a private dermatology clinic. Clinical photographs, ultraviolet (UV) photographs and digital dermatoscopic pictures were also obtained. RESULTS: 15 patients of ethnic Chinese origin had histologically-confirmed exogenous ochronosis. DISCUSSION: The difficulties in differentiating exogenous ochronosis from melasma are discussed and there is a likelihood of under-reporting as the clinical presentation of the condition may be misleading. CONCLUSION: Exogenous ochronosis may exist amongst ethnic Chinese patients with fairer skin-types, contrary to the commonly-accepted perception that it is more prevalent in darker skin-types.

Controlled field studies on soil aquifer treatment in a constructed coastal sandfill.

A controlled artificial recharge experiment was conducted to investigate the effect of soil aquifer treatment during percolation of secondary and tertiary (ultrafiltered) treated wastewater through the shallow vadoze zone of a newly constructed coastal sandfill. The sandfill is a reclaimed land constructed from marine sand dredged from the seabed. To obtain 1-D flow, a stainless steel column was driven to a depth of 2.5 m, penetrating the phreatic surface. Wastewater was percolated through the column under fully-saturated and unsaturated conditions. Infiltration rates, dissolved organic carbon (DOC) and ultra-violet absorption (UVA) were monitored. The wastewaters were recharged at similar infiltration rates of approximately 5.5 m/day and 3.5 m/day under fully-saturated and unsaturated conditions, respectively. In both cases, clogging occurred 40 days after the start of recharge, under saturated conditions. For secondary treated wastewater, DOC concentration (mg/l) reduced by 28% and 13% under unsaturated and saturated conditions, respectively. The corresponding UVA reduction was 19.4% and 14.1%. Similar reductions in DOC were observed for the tertiary treated wastewater; however, the reduction in UVA was higher; 28% and 22% under unsaturated and saturated conditions, respectively. On an mass removal (mg/m(2) DOC) basis, DOC reduction appeared to be more significant under unsaturated conditions. This is attributed to the presence of interstitial oxygen.

Neuroprotective effect of grafting GDNF gene-modified neural stem cells on cerebral ischemia in rats.

Previous studies indicated the beneficial effects of glial cell line-derived neurotrophic factor (GDNF) and transplanted neural stem cells (NSCs) on stroke. Here, we explored whether transplantation of neural stem cells (NSCs) modified by GDNF gene provides a better therapeutic effect than native NSCs after stroke. Primary rat NSCs were transfected with GDNF plasmid (GDNF/NSCs, labeled by green fluorescent protein from AdEasy-1, GFP). Adult rats were subjected to two-hour middle cerebral artery occlusion and reperfusion, followed by infusion of NSCs (labeled with5-bromo-2'-deoxyuridine before infusion, BrdU), GDNF/NSCs and saline at 3 days after reperfusion (NSCs group, GDNF/NSCs group, control group), respectively. All rats were sacrificed at 1, 2, 3, 5, and 7 weeks after reperfusion. Modified Neurological Severity Scores (mNSS) test and H and E staining were respectively performed to evaluate neurological function and lesion volume. Immunohistochemistry was used to identify implanted cells and observe the expressions of Synaptophysin (Syp) and postsynaptic density-95 (PSD-95) and caspase-3. TdT-mediated dUTP-biotin nick-end labeling (TUNEL) was employed to observe apoptotic cells. Western blotting was used to detect brain-derived neurotrophic factor (BDNF) and NT-3 protein expression. Significant recovery of mNSS was found in GDNF/NSCs rats at 2 and 3 weeks after reperfusion compared with NSCs rats. Lesion volume in the NSCs and GDNF/NSCs groups was reduced significantly compared with control group. The number of NSCs in the GDNF/NSCs group was significantly increased in comparison with NSCs group. Moreover, Syp-immunoreactive product at 2 and 3 weeks after reperfusion and PSD-95 immunoreactive product in the GDNF/NSCs group were significantly increased compared with NSCs group. In contrast, caspase-3 positive cells and TUNEL-positive cells in the GDNF/NSCs group were significantly decreased compared with NSCs group. Significant increase of BDNF protein in the GDNF/NSCs and NSCs groups was observed compared to the control group at different time points of reperfusion, and GDNF/NSCs grafting significantly increased BDNF protein expression compared to NSCs grafting. In addition, significant increase of NT-3 protein in GDNF/NSCs and NSCs groups was detected only at 1 week of reperfusion compared to control group. The results demonstrate that grafting NSCs modified by GDNF gene provides better neuroprotection for stroke than NSCs grafting alone.

Use of fluorescein as a ground water tracer in brackish water aquifers.

A drift and pumpback experiment was conducted in a brackish water sandfill. The sandfill was reclaimed from the sea in the eastern part of Singapore and contains sands with low organic and clay/silt contents. The high salinity in the ground water precludes the use of chloride and bromide as tracers in such an environment, and a field experiment was conducted to assess the viability of using fluorescein as a tracer in brackish water aquifers. Nitrate was used as a second tracer to serve as a check. Initial laboratory studies showed that fluorescence was unaffected over the range of electrical conductivity and pH of the ground water. Results from the field experiment show that fluorescein appears to behave conservatively.

Four beams evanescent waves interference lithography for patterning of two dimensional features.

This work presents a theoretical study of using the interference of multiple counter-propagating evanescent waves as a lithography technique to print periodic two dimensional features. The formulation of the three dimensional Cartesian space expression of an evanescent wave is presented. In this work, the evanescent wave is generated by the total internal reflection of a plane wave at the interface between a incident dielectric material and a weakly absorbing transmission medium. The influences of polarization, incident angle and the phase shifting of the incident plane waves on the evanescent wave interference are studied. Numerical simulation results suggest that this technique enables fabrication of periodic two dimensional features with resolution less than one third the wavelength of the irradiation source.

RETRACTED: Characterization of a dehydrin-like phosphoprotein (ECPP44) relating to somatic embryogenesis sin carrot.

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Kimura's disease: a diagnostic and therapeutic challenge.

INTRODUCTION: Kimura's disease (KD) is a rare, benign, chronic inflammatory disease with unknown aetiology. Its manifestation is protean. KD has a predilection for the head and neck area, and typically presents as tumour-like lesions that could be easily misdiagnosed. We review our experience with four recent cases. METHODS: Over a four-year period, all patients admitted to Singapore General Hospital with KD of the head and neck region were retrospectively reviewed. Biodata, presenting symptoms and clinical parameters, especially serum eosinophil levels, preoperative investigations, type of surgical procedures and outcome were documented. RESULTS: Four patients presented with KD of the head and neck and displayed varied manifestations of the disease. All the patients had raised serum eosinophil levels. None of them had renal involvement. Preoperative computed tomography were performed in two of the patients and showed features suggestive of KD. Fine-needle aspiration cytology that was performed in two patients was not useful in the diagnosis. All the patients underwent surgical excision of the lesions. Only one patient had multiple recurrence, both at the original and remote sites in the head and neck. CONCLUSION: The clinical presentation and behaviour of KD is very variable. Preoperative imaging is useful in the diagnosis of the disease but the final diagnosis is histological. Surgical excision is the current treatment of choice but recurrence is common. A high index of suspicion and awareness is vital in the early diagnosis and management of KD.