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Biomedical subjects

T H Lim

Publications and source records attributed to T H Lim.

At least 19 recordsLinked to original sources

Myocardial enhancement pattern in patients with acute myocardial infarction on two-phase contrast-enhanced ECG-gated multidetector-row computed tomography.

AIM: To evaluate the myocardial enhancement pattern of the left ventricle on two-phase contrast-enhanced electrocardiogram (ECG)-gated multidetector computed tomography (MDCT) images in patients with acute myocardial infarction (AMI). METHODS: Two-phase contrast-enhanced ECG-gated MDCT examinations were performed in 16 patients with AMI. The presence, location and pattern of myocardial enhancement were evaluated. MDCT findings were compared with the catheter angiographic results. RESULTS: Subendocardial (n = 9) or transmural (n = 6) area of early perfusion defects of the myocardium was detected in 15 of 16 patients (94%) on early-phase CT images. Variable delayed myocardial enhancement patterns on late-phase CT images were observed in 12 patients (75%): (1) subendocardial residual perfusion defect and subepicardial late enhancement (n = 6); (2) transmural late enhancement (n = 1); (3) isolated subendocardial late enhancement (n=1); and (4) isolated subendocardial residual perfusion defect (n = 2). On catheter angiography, 14 of 15 corresponding coronary arteries showed significant stenosis. CONCLUSION: Variable abnormal myocardial enhancement pattern was seen on two-phase, contrast-enhanced ECG-gated MDCT in patients with AMI. Assessment of myocardial attenuation on CT angiography gives additional information of the location and extent of infarction.

Adult↗

Resolution of severe macular oedema in adult Coat's syndrome with high-dose intravitreal triamcinolone acetonide.

OBJECTIVE: To report the clinical outcome of a patient who received high-dose intravitreal triamcinolone acetonide as treatment for severe macular oedema secondary to adult Coat's syndrome. METHOD: Case report. RESULTS: A 74-year-old Indian man complaining of chronic gradual blurring of vision in the left eye was found to have adult Coat's syndrome with severe macular oedema. He received 25 mg of intravitreal triamcinolone acetonide following unsuccessful resolution with grid laser. Optical coherence tomography (OCT) demonstrated up to 75% decrease in macular oedema that was evident even after 9 months follow-up. However, there was no significant improvement in visual acuity. CONCLUSION: Intravitreal triamcinolone is a reasonable option in reducing severe macular oedema in cases of adult Coat's syndrome.

Aged↗

Effect of ganciclovir on the hydrolytic degradation of poly(lactide-co-glycolide) microspheres.

Ganciclovir (GCV)-loaded poly(lactide-co-glycolide) (PLGA) microspheres, 125 +/- 11 mum in diameter, are produced using the emulsification/solvent evaporation technique. The release rate of the drug is studied for 20 weeks in a phosphate-buffered solution of pH 7 at 37 degrees C. The release of the drug shows a triphasic release pattern, i.e., an initial burst, a diffusive phase, and a second burst. The initial burst occurs within the first 2 days of immersion. After the burst, the release is by diffusion for up to 13 weeks, followed by another burst release, which signals the onset of bulk degradation of the PLGA polymer. The presence of GCV molecules decreases the hydrolytic rate of PLGA degradation. Gel permeation chromatography (GPC), differential scanning calorimetry (DSC), field emission scanning electron microscopy (FESEM), and ultraviolet (UV) spectroscopy are used to assess the hydrolytic degradation and drug release rate of the microspheres.

Absorbable Implants↗

Epidemiology of pterygium on a tropical island in the Riau Archipelago.

OBJECTIVES: To describe the epidemiology of pterygium among residents of an island in Indonesia and to examine the roles of age and gender as determinants of bilaterality and severity of the disease. METHODS: Voluntary eye screening on Pulau Jaloh, Riau Archipelago, Indonesia. Gender difference was tested using the chi2 test. The difference in age between subjects with and without disease was tested using unpaired Student's t-test. Odds ratio (relative risk) for gender was calculated using logistic regression model with adjustment for age. RESULTS: Of the 550 inhabitants, 477 (86.7%) responded to the eye screening. The overall prevalence rate of pterygium was 17.0%. Out of 211, 48 male (22.7%) and 33 out of 266 female subjects (12.4%) had the disorder, with the gender difference being statistically significant. Adjusted for age, the risk of disease was 3.1-fold higher among the males. In all, 71.6% of subjects with pterygium had bilateral disease. Subjects with pterygium were significantly older, their mean age being 42.9 years compared to 18.7 years among those without disease. The prevalence rates in male subjects increased from age 20 to reach a plateau of 63.6% at age 35 and remained stable thereafter. In the female subjects, the rates also increased with age, albeit at a slower rate, from age 20 to reach a plateau of 46.7% at age 55 and remained stable thereafter. CONCLUSIONS: There is a high prevalence rate of pterygium among the study subjects, with the rates increasing rapidly with age.

Adolescent↗

Sustained release of ganciclovir from poly(lactide-co-glycolide) microspheres.

Biodegradable poly(lactide-co-glycolide) microspheres loaded with ganciclovir were produced using the emulsification/solvent evaporation technique. The effects of drug-to-polymer ratio and dispersion time on the drug content in the microspheres were investigated. The release rate of the drug was studied for 20 weeks in a phosphate buffered solution of pH 7 at 37 degrees C. Data revealed that lower drug content was obtained with increasing drug-to-polymer ratio and decreasing dispersion time. The release of the drug followed a triphasic release pattern, i.e. an initial burst, a diffusive phase and a second burst. The initial burst occurred within the first 2 days of immersion. After the burst, the release was by diffusion for up to 13 weeks, followed by another burst release, which signals the onset of bulk degradation of the polymer. Gel permeation chromatography (GPC), differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and ultraviolet spectroscopy (UV) were used to follow the hydrolytic degradation and drug release rate of the microspheres.

Antiviral Agents↗

The incidence and patterns of BCR/ABL rearrangements in chronic myeloid leukaemia (CML) using fluorescence in situ hybridisation (FISH).

INTRODUCTION: Chronic myeloid leukaemia (CML) is characterised by the formation of the BCR/ABL fusion gene, usually as a result of the Philadelphia (Ph) translocation between chromosomes 9 and 22. MATERIALS AND METHODS: The incidence of both typical and atypical BCR/ ABL gene rearrangements was determined in 110 patients suspected of CML using dual fusion fluorescence in situ hybridisation (DF-FISH) probes. RESULTS: Eighty-seven per cent of CML patients showed Ph translocation while 13% were negative for the Ph chromosome. About 71.9% of Ph-positive patients displayed the typical DF-FISH signal pattern. Atypical patterns among the Ph-positive patients included the concurrent loss of residual proximal 9q and distal 22q (10.4%), complex translocation with additional partners (9.4%), supernumerary Ph (3.1%), loss of residual 9q sequences proximal to breakpoint (3.1%), and deletion of distal derivative 22q signal (2.1%). Cryptic genetic alterations with loss of proximal 9q sequences were found in 13.5% of CML Ph-positive patients, which is associated with poor prognosis. Fusion signals were detected in 57.1% of CML Ph-negative patients, indicating cryptic BCR/ABL rearrangements (i.e., masked Ph). CONCLUSION: FISH is able to detect BCR/ABL fusion in CML with masked or variant Ph not apparent with conventional karyotyping. Establishment of signal patterns with FISH is important as atypical patterns may have clinical prognostic implications.

Gene Rearrangement↗

Sperm segregation patterns by fluorescence in situ hybridization studies of a 46,XY,t(2;6) heterozygote giving rise to a rare triploid product of conception with a 69,XXY,t(2;6)(p12;q24)der(6)t(2;6)(p12;q24)pat karyotype.

A blighted ovum diagnosed initially by ultrasound was determined to be a partial hydatidiform mole with a 69,XXY,t(2;6)(p12;q24)der(6)t(2;6)(p12;q24)pat karyotype by cytogenetic analysis. The triploid state arose through dispermy in which both spermatozoa carried rearranged chromosomes, one carrying a balanced translocation through alternate segregation and the other an unbalanced derivative chromosome 6 through adjacent 1 segregation. Segregation analysis of 7,000 spermatozoa from the father was performed with a three-color fluorescence in situ hybridization (FISH) protocol using alpha-satellite 6, telomeric 2p, and telomeric 6q probes. Segregation frequencies of normal and balanced products (alternate segregation), adjacent 1, adjacent 2, and 3:1 were 49.9%, 42.4%, 2.5%, and 4.2%, respectively. The high percentage of alternate segregation is consistent with the knowledge of their preferential outcome. However, the high incidence of adjacent 1 sperm highlights the abnormality risk. Alternate and adjacent 1 segregations (92.3%) accounted for the observed rearranged chromosomes in the triploid. The most viable imbalanced combination would be the one carrying the der(6) chromosome, but since the unbalanced segment comprises 3.6% of the haploid autosomal length (HAL), no risk of a viable imbalanced offspring is indicated. However, an increased likelihood of recurrent miscarriages is likely, and this is confirmed by the couple's two earlier miscarriages. Sperm segregation patterns of translocation carriers determined by FISH can help in ascertaining expected and unexpected karyotypes. The high frequency of adjacent 1 products shows that the presence of the additional derivative chromosome in the partial mole, though rare in occurrence, should be less surprising.

Aneuploidy↗

Restoration of large bone defects using a hard-setting, injectable putty containing demineralized bone particles compared to cancellous autograft bone.

An injectable, hard-setting, calcium sulfate-based putty containing demineralized bone matrix particles (AlloMatrix II, Wright Medical Technology, Inc, Arlington, Tenn) was compared to autogenous cancellous bone graft to evaluate healing in a canine model. Area fraction of new bone, modulus of elasticity, and compressive strength of new bone were evaluated, as was radiographic and histologic healing. Bilateral defects were created in the proximal humeri, and each defect was implanted with either the putty or autogenous bone according to a randomized schedule. Dogs were euthanized at 6, 13, and 26 weeks. The area fraction, modulus of elasticity, and compressive strength of newly formed bone was not significantly different between the putty and autogenous bone at 6, 13, or 26 weeks. The putty had excellent handling characteristics, was biocompatible, and was as effective as autograft bone in achieving near complete bony restoration of a large, critical-sized defect.

Animals↗

Healing of large defects treated with calcium sulfate pellets containing demineralized bone matrix particles.

Calcium sulfate (OsteoSet, Wright Medical Technology, Inc, Arlington, Tenn) and calcium sulfate/demineralized bone matrix (DBM) pellets (OsteoSet DBM, Wright Medical Technology, Inc) have been evaluated preclinically in a bilateral medullary defect model of a canine humerus. In this model, both short (6 week) and long (26 week) time points have been evaluated. An analysis of bone response to the pellets was conducted using radiological, histological, mechanical, and quantification techniques. The calcium sulfate/DBM pellets exhibited more rapid trabecular bone remodeling as demonstrated by the absence of the ringlet bone structure typically seen with calcium sulfate pellets. We concluded that calcium sulfate and calcium sulfate/DBM pellets are both effective bone graft substitutes.

Animals↗

Well-differentiated thyroid carcinoma: factors predicting recurrence and survival.

AIMS: 1) Determine the patient and tumour characteristics for well-differentiated thyroid carcinoma--towards developing a unique risk classification for our largely Chinese population. 2) Assess extent of thyroid surgery required. 3) Document prognostic value of UICC and AMES classification. METHODS: Retrospective review of 175 patients treated for primary thyroid epithelial malignancy by the Department of General Surgery at the Singapore General Hospital. RESULTS: There were 78% papillary carcinomas (PC) and 19% follicular carcinomas (FC). Female: male ratio was 3:1. Patient distribution in the UICC stages I, II, III, IV is respectively 56, 11, 31 and 2%. Twenty-six percent had hemithyroidectomy, and 74% total thyroidectomy. Neck dissections were required in 6% of FC compared to 34% of PC. Mean follow-up was 40 months. Extent of surgery did not affect PC/FC survival nor recurrence rates (p=0.53 and 0.06 respectively). Recurrences occurred in 15% FC and 9% PC. Death occurred in one FC and two PC. Survival correlated with UICC stage I/II and stage III/IV groups (p=0.04), and recurrence correlated with AMES High and Low Risk groups (p=0.004). No statistically significant difference was shown for survival between PC and FC or AMES groups and recurrence between PC and FC or UICC groups. CONCLUSIONS: Extent of thyroid surgery does not significantly affect local recurrences of PC/FC. The characterisation of thyroid carcinoma here is an important step towards developing a risk classification unique to our largely Chinese population.

Adenocarcinoma, Follicular↗

Biomechanical evaluation of diagonal fixation in pedicle screw instrumentation.

STUDY DESIGN: Flexibility tests and finite element analyses were performed for the biomechanical evaluation of diagonal transfixation in pedicle screw instrumentation. OBJECTIVE: To assess the biomechanical advantages of diagonal transfixation compared with conventional horizontal transfixation. SUMMARY AND BACKGROUND DATA: A few pedicle screw instrumentation systems allow the use of cross-links in the diagonal direction. Such a diagonal transfixation is anticipated to improve the surgical construct stability, but its biomechanical qualities have not been completely evaluated. METHODS: Flexibility tests were performed on 10 calf lumbar spines (L2-L5). Specimens were subjected to pure moments up to 8.2 Nm in flexion, extension, lateral bending, and extension while the resulting movements of L3 and L4 were measured by a three-dimensional motion analysis system. The tested cases included (1) intact, (2) pedicle screw fixation without transfixation after total removal of the L3-L4 disc, (3) pedicle screw fixation with diagonal transfixation, and (4) pedicle screw fixation with horizontal transfixation. Three-dimensional finite element models of the tested surgical constructs were also developed by use of three-dimensional beam elements to investigate the effect of diagonal transfixation and horizontal transfixation on the construct stability and the corresponding stress changes in the screws. RESULTS: When compared with no transfixation, horizontal transfixation significantly improved the lateral bending and axial rotation stability by 15.7% and 13.9%, respectively, but there was no improvement of stability in flexion and extension. By contrast, diagonal transfixation significantly improved the flexion and extension stability by 12% and 10.7%, respectively, but not the lateral bending and axial rotation stability in comparison with no transfixation. Comparison between horizontal transfixation and diagonal transfixation showed that the stabilizing effect of diagonal transfixation was greater in flexion and extension (13% and 11%, P < 0.01) than that of horizontal transfixation but smaller in lateral bending (11%, P < 0.05) and axial rotation (6.6%, P > 0.1). Finite element model predictions of the motion changes were similar to the changes observed in flexibility tests. In horizontal transfixation, the load changes, compared with no transfixion, were a 0.02% increase in flexion-extension, a 27.5% increase in lateral bending, and a 58% decrease in axial rotation, and the magnitudes of the moments applied on both the right and left pedicle screws were identical. However, when diagonal transfixation was achieved by connecting the left superior screw and the right inferior screw, the loads in the left screw were increased by 11.5% in flexion-extension, 43.6% in lateral bending, and 7.9% in axial rotation, whereas the loads in the right screw were decreased by 10.9% in flexion-extension, increased by 0.06% in lateral bending, and decreased by 18.1% in axial rotation. CONCLUSIONS: The results of this study showed that diagonal transfixation provides more rigid fixation in flexion and extension but less in lateral bending and axial rotation in comparison with horizontal transfixation. Furthermore, greater stresses in the pedicle screws were predicted in the diagonal transfixation model. These limitations of diagonal transfixation should be considered carefully for clinical application.

Animals↗

Novel 6-substituted uracil analogs as inhibitors of the angiogenic actions of thymidine phosphorylase.

Thymidine phosphorylase (TP) catalyzes the reversible phosphorolysis of thymidine and other pyrimidine 2'-deoxyribonucleosides. In addition, TP has been shown to possess angiogenic activity in a number of in vitro and in vivo assays, and its angiogenic activity has been linked to its catalytic activity. A series of 5- and 6-substituted uracil derivatives were synthesized and evaluated for their abilities to inhibit TP activity. Among the most active compounds was a 6-amino-substituted uracil analog, 6-(2-aminoethyl)amino-5-chlorouracil (AEAC), which was a competitive inhibitor with a K(i) of 165 nM. The inhibitory activity of AEAC was selective for TP, as it did not inhibit purine nucleoside phosphorylase or uridine phosphorylase at concentrations up to 1 mM. Human recombinant TP induced human umbilical vein endothelial cell (HUVEC) migration in a modified Boyden chamber assay in vitro, and this action could be abrogated by the TP inhibitors. The actions of the inhibitors were specific for TP, as they had no effect on the chemotactic actions of vascular endothelial growth factor (VEGF). HUVEC migration was also induced when TP-transfected human colon and breast carcinoma cells were co-cultured in the Boyden chamber assay in place of the purified angiogenic factors, and a TP inhibitor blocked the tumor cell-mediated migration almost completely. These studies suggest that inhibitors of TP may be useful in pathological conditions that are dependent upon TP-driven angiogenesis.

Angiogenesis Inhibitors↗

Prognostic significance of cerebral metabolic abnormalities in patients with congestive heart failure.

BACKGROUND: Cerebral metabolic abnormalities were proposed as a potential marker of disease severity in congestive heart failure (CHF), but their prognostic significance remains uncertain. METHODS AND RESULTS: We investigated the prognostic value of cerebral metabolic abnormalities in 130 consecutive patients with advanced CHF (100 men aged 42.6+/-11.9 years; left ventricular ejection fraction, 22.2+/-6.2%). Proton magnetic resonance spectroscopy data were obtained from localized regions ( approximately 8 mL) of the occipital gray matter and the parietal white matter. The primary end point was the occurrence of death after the proton magnetic resonance spectroscopy. During follow-up (18.5+/-14.4 months), 21 patients died and 15 underwent urgent heart transplantation. In the Cox proportional model, occipital metabolites (N-acetylaspartate, creatine, choline, and myoinositol), parietal N-acetylaspartate level, and the duration of CHF symptoms (>12 months) were validated as univariate predictors of death. In multivariate Cox analyses, however, the occipital N-acetylaspartate level was an independent predictor of death (hazard ratio, 0.52; 95% CI, 0.41 to 0.67; P<0.001). An analysis with respect to the combined end point of death or urgent transplantation showed similar results. The best cutoff value (9.0 mmol/kg) for occipital N-acetylaspartate level had 75% sensitivity and 67% specificity to predict mortality. CONCLUSIONS: The occipital N-acetylaspartate level is a powerful and independent predictor of CHF mortality, suggesting that cerebral metabolic abnormalities may be used as a new prognostic marker in the assessment of patients with CHF.

Adult↗

Morphologic changes in the lumbar intervertebral foramen due to flexion-extension, lateral bending, and axial rotation: an in vitro anatomic and biomechanical study.

STUDY DESIGN: A biomechanical and anatomic study with human cadaveric lumbar spine. OBJECTIVES: The purpose of this study is to examine the morphologic changes in the intervertebral foramen during flexion, extension, lateral bending, and axial rotation of the lumbar spine and to correlate these changes with the flexibility of the spinal motion segments. SUMMARY OF BACKGROUND DATA: Previous studies showed morphologic changes in the intervertebral foramen during flexion and extension; however, those changes during lateral bending and axial rotation were not well known. METHODS: There were 81 motion segments obtained from 39 human cadaveric lumbar spines (mean age 69 years). The motion segments were imaged with CT scanner with 1-mm thick consecutive sections. For biomechanical testing each motion segment was applied with incremental pure moments of flexion, extension, lateral bending, and axial rotation. Rotational movements of the motion segment were measured using VICON cameras. After application of the last load, the specimens were frozen under load, and then CT was performed with the same technique described above. Six parameters of the intervertebral foramen were measured, including foraminal width (maximum and minimum), foraminal height, disc bulging, thickness of ligamentum flavum, and cross-sectional area of the foramen. RESULTS: Flexion increased the foraminal width (maximum and minimum), height, and area significantly while significantly decreasing the disc bulging and thickness of ligamentum flavum (P < 0.05). However, extension decreased the foraminal width (maximum and minimum), height, and area significantly. Lateral bending significantly decreased the foraminal width (maximum and minimum), height, and area at the bending side, whereas lateral bending significantly increased the foraminal width (minimum), height, and area at the opposite side of bending. Likewise, axial rotation decreased the foraminal width (minimum) and area at the rotation side significantly while significantly increasing the foraminal height and foraminal area at the opposite side. The percent change in the foraminal area was found significantly correlated with the amount of segmental spinal motion except for the extension motion. CONCLUSIONS: This study showed that the intervertebral foramen of the lumbar spine changed significantly not only on flexion-extension but also on lateral bending and axial rotation. The percent change in cross-sectional foraminal area was correlated with the amount of segmental motion except for extension motions. Further studies are needed to assess the morphologic changes in the intervertebral foramen in vivo and to correlate clinically.

Adult↗

Effect of endplate conditions and bone mineral density on the compressive strength of the graft-endplate interface in anterior cervical spine fusion.

STUDY DESIGN: Destructive compression tests and finite element analyses were conducted to investigate the biomechanical strength at the graft-endplate interface in anterior cervical fusion. OBJECTIVES: To investigate the effect of endplate thickness, endplate holes, and bone mineral density of the vertebral body on the biomechanical strength of the endplate-graft interface in an anterior interbody fusion of the cervical spine. SUMMARY OF BACKGROUND: Subsidence of the graft into the vertebral body is a well-known complication in anterior cervical fusion. However, there is no information in the literature regarding the compressive strength of the graft-endplate interface in relation to the endplate thickness, holes in the endplate, and bone mineral density of the vertebral body. METHODS: Biomechanical destructive compression tests and finite element analyses were performed in this study. Cervical vertebral bodies (C3-C7) isolated from seven cadaveric cervical spines (age at death 69-86 years, mean 79 years) were used for compression tests. Bone mineral density of each vertebral body was measured using a dual energy radiograph absorptiometry unit. Endplate thickness was measured using three coronal computed tomography images of the middle portion of the vertebral body obtained using a computer-assisted imaging analysis. Then each vertebral body was cut into halves through the horizontal plane. A total of 54 specimens, consisting of one endplate and half of the vertebral body, were obtained after excluding eight vertebrae with gross pathology on plain radiograph. Specimens were assigned to one of three groups with different endplate conditions (Group I, intact; Group II, partial removal; and Group III, complete removal) so that group mean bone mineral density became similar. Each endplate was slowly compressed until failure using an 8-mm-diameter metal indenter, and the load to failure was determined as a maximum force on a recorded force-displacement curve. The effect on the strength of the graft-endplate interface of various hole patterns in the endplate was studied using a finite element technique. The simulatedhole patterns included the following: one large central hole, two lateral holes, two holes in the anterior and posterior portion of the endplate, and four holes evenly distributed from the center of the endplate. Stress distribution in the endplate was predicted in response to an axial compressive force of 110 N, and the elements with von Mises stress greater than 4.0 MPa were determined as failed. RESULTS: The endplate thickness and bone mineral density were similar at all cervical levels, and the superior and inferior endplates had similar thickness at all cervical levels. There was no significant association between bone mineral density and endplate thickness. Load to failure was found to have a significant association with bone mineral density but not with endplate thickness. However, load to failure tends to decrease with incremental removal of the endplate, and load to failure of the specimens with an intact endplate was significantly greater than that of the specimens with no endplate. Finite element model predictions showed significant influence of the hole pattern on the fraction of the upper endplate exposed to fracture stress. A large hole was predicted to be more effective than the other patterns at distributing a compressive load across the remaining area and thus minimizing the potential fracture area. CONCLUSION: Results of this study suggest that it is important to preserve the endplate as much as possible to prevent graft subsidence into the vertebral body, particularly in patients with poor bone quality. It is preferable to make one central hole rather than multiple smaller holes in the endplate for vascularity of the bone graft because it reduces the surface area exposed to fracture stresses.

Aged↗