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Biomedical subjects

T C Lee

Publications and source records attributed to T C Lee.

At least 19 recordsLinked to original sources
PubMed2006

Re-engineering Colles: form, function and fragility fractures.

Of the twenty nine anatomy professors in the Royal College of Surgeons in Ireland, primus inter pares is Abraham Colles. In his 1811 book A Treatise on Surgical Anatomy he revolutionised the subject by teaching it topographically, seeking "to describe the relative position of the parts and to point out the subservience of anatomical knowledge to surgical practice". Today we have extended this to 'clinical practice' and, in the Anatomy Room, students are guided through each region by clinically trained staff, from surface anatomy via three-dimensional dissection to radiological images. This is augmented by online histology and radiology courses and DVDs in which dissection footage, edited by a content analysis engine, is used to preview and review practical classes. In the same book, Colles also wrote that 'the fixed and immutable laws of mathematics are little applicable to the science of medicine'. Computer-aided learning argues against this. So does research which links fatigue microdamage to bone remodelling and the development of algorithms to predict, and thus prevent, osteoporotic fractures. Mechanical principles are being used to develop scaffolds for tissue engineering and to optimise the mechanical environment of seeded mesenchymal stem cells. While Colles' teaching approach holds true, in biomechanics, tissue engineering and computing, mathematical laws are now being successfully applied to medical science.

Anatomy↗
PubMed2006

Osteonal crack barriers in ovine compact bone.

Bone is an anisotropic structure which can be compared to a composite material. Discontinuities within its microstructure may provide stress concentration sites for crack initiation, but act as a barrier to its propagation. This study looks specifically at the relationship between crack length and propagation in compact bone. Beam-shaped bone samples from sheep radii were prepared and stained with fluorochrome dyes and tested in cyclic fatigue under four-point bending in an INSTRON 1341 servo-hydraulic fatigue-testing machine. Samples were tested at a frequency of 30 Hz and stress range of 100 MPa under load control. Specimens were sectioned transversely using a diamond saw, slides prepared and examined using epifluorescence microscopy. Cracks in transverse sections were classified in terms of their location relative to cement lines surrounding secondary osteons. Mean crack length, crack numerical density and crack surface density were examined. Short microcracks (100 microm or less) were stopped at the cement lines surrounding osteons, microcracks of intermediate length (100-300 microm) were deflected as they hit the cement line, and microcracks that were able to penetrate through cement lines were longer (> 400 microm). These data show that bone microstructure allows the initiation of microcracks but acts as a barrier to crack propagation.

Animals↗
PubMed2006

Microcracks in compact bone: a three-dimensional view.

Microcracks have been implicated in the loss of bone quality for osteoporosis. In order to detect and monitor their growth, and to use these data to predict fractures, it is essential to obtain quantitative data regarding their shape in three dimensions. Beam-shaped bone samples from sheep radii were prepared and stained with fluorochrome dyes and tested in cyclical fatigue under four-point bending in a servo-hydraulic fatigue-testing machine. Samples were tested at a frequency of 30 Hz under load control at a stress range of 100 MPa. Holes were drilled into bone samples and used as reference points for reconstructions. A series of thin longitudinal sections were cut using a sledge macrotome. A two-dimensional image of each section was examined using an epifluorescence microscope and images transferred to a PC via a CCD low-light colour video camera. A three-dimensional image of each microcrack was reconstructed using computer software, and its dimensions measured. Cracks were elliptical in shape, longer in the longitudinal direction and with a mean aspect ratio of 5.5 +/- 1.05. The mean (+/- SD) length and width of labelled microcracks were 488 +/- 151 and 88 +/- 21 microm, respectively.

Animals↗
PubMed2006

Microdamage and bone mechanobiology.

Mechanobiology is concerned with the relationships between mechanical forces and biological processes. Bone adapts to altered mechanical loading by modelling and remodelling. Microdamage is a stimulus for adaptation as shown by a sheep overload model. If microdamage accumulates it leads to fracture failure, notably in osteoporosis. Detection methods, based on chelating fluorochromes and radiopaque agents, will enable microdamage to be quantified and, along with bone mass, aid in fracture prediction and prevention. Mechanobiological principles can be utilised to create tissue engineered bone grafts in cases of bone loss due to trauma, malignancy or resorption.

Adaptation, Physiological↗
PubMed2005

The effect of pancreatic islet transplantation on progression of diabetic retinopathy and neuropathy.

INTRODUCTION: Pancreatic islet transplantation (PIT) has only become an effective treatment for type 1 diabetes mellitus within the past 4 years. As a result, the long-term effects of PIT on progression of diabetic neuropathy and retinopathy are unknown. The benefit of halting or improving diabetic neuropathy and retinopathy is of particular interest since most PIT recipients have not developed the advanced complications of diabetes. Herein, we describe the improvement and stabilization of diabetic neuropathy and retinopathy in 12 PIT recipients. PATIENTS AND METHODS: Between January 1, 2002, and June 30, 2004, there have been 12 patients who have received PIT. Currently, there are eight patients who have sufficient follow-up to assess the progression of diabetic retinopathy and neuropathy. To assess for disease progression, patients were examined by a single ophthalmologist and single neurologist throughout the study period. Eye exams were performed using a slit-lamp exam while neurological status was assessed using electromyelograms and clinical exams. RESULTS: All PIT recipients had decreases in hemoglobin A(1)C and increases in serum C-peptide. All study patients had stabilization of their retinopathic disease. One patient demonstrated improvement of retinopathy at 1 year posttransplant. Fifty percent of patients demonstrated improvement or stabilization of their diabetic neuropathy. One patient had mild reinnervation of the fingers and wrist extensors by clinical exam 1 year posttransplant. Four patients exhibited an average decrease of 19% in sural nerve conduction velocities. CONCLUSION: Our series has demonstrated that all PIT recipients have had stabilization of their diabetic retinopathy and that 50% of patients exhibited stabilization or even improvement of their diabetic neuropathy.

Adult↗
PubMed2005

Gastroschisis and biliary atresia in a neonate: uncommon presentation or common precipitant.

We report here on a newborn infant who initially presented with a history of gastroschisis, abdominal distension, and jaundice. Further studies revealed that the child had findings consistent with extrahepatic biliary atresia (EHBA). The child later developed hepatic failure and subsequently expired. The purpose of this case report is to discuss the pathogenesis of each disease process and to identify any commonality between the pathogenesis of gastroschisis and EHBA.

Biliary Atresia↗
PubMed2005

Systemic carboplatin for retinoblastoma: change in tumour size over time.

BACKGROUND/AIM: Chemotherapy for intraocular retinoblastoma is used to shrink individual retinal tumours to a size amenable to focal treatments. Quantitative data regarding retinal tumour response following treatment with primary systemic carboplatin are reported. METHODS: Changes in area and largest basal diameter of tumours that were exposed to carboplatin, had no concomitant focal treatment, and had digital funduscopic photography performed before and after treatment, were measured. Response was evaluated. RESULTS: 36 tumours were measured following one treatment: 34/36 (94.4%) responded, with a 37.1% mean decrease in area (median = 37.0%; range 4.0%-76.7%). Mean reduction in basal diameter was 21.3% (med = 21.0%; -7.9%-52.5%). 20 tumours were treated with a second cycle: 15/20 (75.0%) responded. Mean decrease in area was 17.8% (med = 15.3%; -7.0%-49.7%). The mean cumulative decrease in area after two treatments was 55.1% (med = 56.2%; 33.0%-74.5%). Mean cumulative reduction in basal diameter was 33.6% (med = 33.6%; 10.9%-53.2%). 12 tumours were treated with a third cycle: 3/12 (25.0%) responded, 8/12 were stable, and one progressed. Mean decrease in area was 5.4% (med = 7.2%; -17.7%-20.6%). Cumulative decrease in area after three treatments was 58.1% (med = 57.3%; 34.8%-77.2%). Mean cumulative reduction in basal diameter was 38.8% (med = 38.2%; 19.1%-54.1%). CONCLUSIONS: Carboplatin caused measurable shrinkage of retinoblastoma tumours. Response was greatest following the initial treatment and decreased with subsequent treatments.

Antineoplastic Agents↗
PubMed2005

Membrane bioreactors for water reclamation.

Singapore has been using dual membrane technology (MF/UF RO) to produce high-grade water (NEWater) from secondary treated sewage. Membrane bioreactor (MBR) has very high potential and will lead to the further improvement of the productivity and quality of high-grade water. This study was focused on the technical feasibility of MBR system for water reclamation in Singapore, making a comparison between various membrane systems available and to get operational experience in terms of membrane cleaning and other issues. Three MBR plants were built at Bedok Water Reclamation Plant with a design flow of 300 m3/day each. They were commissioned in March 2003. Three different types of submerged membranes were tested. They are Membrane A, plate sheet membrane with pore size of 0.4 microm; Membrane B, hollow fibre membrane with pore size of 0.4 microm; and Membrane C, hollow fibre membrane with pore size of 0.035 microm. The permeate quality of all the three MBR Systems were found equivalent to or better than that of the conventional tertiary treatment by ultrafiltration. MBR permeate TOC was about 2 mg/l lower than UF permeate TOC. GC-MS, GC-ECD and HPLC scan results show that trace organic contaminants in MBR permeate and UF permeate were in the same range. MBR power consumption can be less than 1 kwh/m3. Gel layer or dynamic membrane generated on the submerged membrane surface played an important role for the lower MBR permeate TOC than the supernatant TOC in the membrane tank. Intensive chemical cleaning can temporarily remove this layer. During normal operation conditions, the formation of dynamic membrane may need one day to obtain the steady low TOC levels in MBR permeate.

Bioreactors↗
PubMed2004

Genetic polymorphism of cytochrome P450 2C19 in healthy Malaysian subjects.

AIMS: 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. METHODS: Study subjects were 142 healthy, unrelated Malaysians aged 18-29 years. Baseline omeprazole and 2-h postingestion omeprazole and 5'-hydroxyomeprazole concentrations were measured for CYP2C19 phenotype determination. Identification of CYP2C19 genotypes was performed with the use of polymerase chain reaction. RESULTS: Phenotyping of CYP2C19 revealed that the prevalence of poor metabolizers (PMs) in the Malaysian population was 14.1%, whereas prevalence of PMs in genotyping was 12.6%. The PM genotypic prevalence rate was 5.6% in Malays, 19.1% in Chinese and 10.0% in Indian subjects. There were significant differences in PM genotypic prevalence rates among the three primary ethnic groups (P < or = 0.05). CONCLUSIONS: Phenotyping and genotyping revealed significant differences in the prevalence rates among the three ethnic groups in Malaysia, with Chinese recording highest prevalence.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2003

The cellular transducer in damage-stimulated bone remodelling: a theoretical investigation using fracture mechanics.

This paper reports on some theoretical work which used fracture mechanics concepts to draw conclusions about the nature of the so-called 'cellular transducer': the means by which bone cells detect the presence of damage and thus initiate remodelling and adaptation activities. Using analytical and numerical methods, we estimated the strains and displacements around cracks of the typical size, shape and orientation that normally occur in compact bone. We predicted that it is not possible for osteocytes or their processes to be fractured as a result of direct tensile strains, because the strains generated are much less than the expected failure strains of cellular material. We proposed a new failure mechanism by which osteocyte processes spanning the crack are cut by shearing motions between the crack faces. We predicted that failures of this type can occur. Failures begin to occur if crack lengths become greater than normal (100 microm), so this could act as a signal to initiate repair processes for individual cracks. Very large numbers of cell processes (greater than 1000) will fail if the crack length and/or applied stress reach dangerous levels (300 microm and 60 Mpa, respectively) at which point bone deposition may be required to prevent stress fractures. Similar results also occurred if we proposed a different mechanism of damage detection, involving cells' ability to detect the high levels of strain that occur near crack tips. This work, though based on theoretical mechanics considerations, suggests some biological experiments which might confirm our findings.

Bone Remodeling↗
PubMed2003

The fatigue strength of compact bone in torsion.

We have conducted a series of fatigue tests on samples of bovine compact bone loaded in cyclic torsion. The fatigue strength (i.e. the range of stress needed to cause failure in a given number of cycles) was found to be lower than the fatigue strength of the same material in compression by more than a factor of two. We also tested intact chicken metatarsals and found a similar reduction in strength compared to compression testing of chicken tibiae. These results were predicted using a theoretical model in which fatigue failure was assumed to be dependent on the growth of microcracks, oriented approximately parallel to the bone's longitudinal axis but having misorientation angles of up to 30 degrees. An effective stress range was derived which is a function of the normal and shear stresses, and thus of the Mode I and Mode II stress intensities experienced by the crack. These results may have important consequences for the understanding of fatigue in bone in vivo; relatively small amounts of longitudinal shear stress, which are often ignored in analysis, may contribute significantly to fatigue failures. This may shed light on the phenomenon of stress fractures and on the need for repair and adaptation in living bone.

Animals↗
PubMed2003

Evidence of an interaction between nifedipine and nafcillin in humans.

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.

Adult↗
PubMed2003

Microdamage and mechanical behaviour: predicting failure and remodelling in compact bone.

This paper reports on the development of a theoretical model to simulate the growth and repair of microdamage in bone. Unlike previous theories, which use simplified descriptions of damage, this approach models each individual microcrack explicitly, and also models the basic multicellular units (BMUs) that repair cracks. A computer simulation has been developed that is capable of making a variety of predictions. Firstly, we can predict the mechanical behaviour of dead bone in laboratory experiments, including estimates of the number of cycles to failure and the number and length of microcracks during fatigue tests. Secondly, we can predict the results of bone histomorphometry, including such parameters as BMU activation rates and the changing ratio of primary to secondary bone during ageing. Thirdly, we can predict the occurrence of stress fractures in living bone: these occur when the severity of loading is so great that cracks grow faster than they can be repaired. Finally, we can predict the phenomenon of adaptation, in which bone is deposited to increase cortical thickness and thus prevent stress fractures. In all cases results compare favourably with experimental and clinical data.

Adaptation, Physiological↗
PubMed2003

Detecting microdamage in bone.

Fatigue-induced microdamage in bone contributes to stress and fragility fractures and acts as a stimulus for bone remodelling. Detecting such microdamage is difficult as pre-existing microdamage sustained in vivo must be differentiated from artefactual damage incurred during specimen preparation. This was addressed by bulk staining specimens in alcohol-soluble basic fuchsin dye, but cutting and grinding them in an aqueous medium. Nonetheless, some artefactual cracks are partially stained and careful observation under transmitted light, or epifluorescence microscopy, is required. Fuchsin lodges in cracks, but is not site-specific. Cracks are discontinuities in the calcium-rich bone matrix and chelating agents, which bind calcium, can selectively label them. Oxytetracycline, alizarin complexone, calcein, calcein blue and xylenol orange all selectively bind microcracks and, as they fluoresce at different wavelengths and colours, can be used in sequence to label microcrack growth. New agents that only fluoresce when involved in a chelate are currently being developed--fluorescent photoinduced electron transfer (PET) sensors. Such agents enable microdamage to be quantified and crack growth to be measured and are useful histological tools in providing data for modelling the material behaviour of bone. However, a non-invasive method is needed to measure microdamage in patients. Micro-CT is being studied and initial work with iodine dyes linked to a chelating group has shown some promise. In the long term, it is hoped that repeated measurements can be made at critical sites and microdamage accumulation monitored. Quantification of microdamage, together with bone mass measurements, will help in predicting and preventing bone fracture failure in patients with osteoporosis.

Animals↗
PubMed2003

An anatomical study of the cutaneous branches of the mental nerve.

Minor surgical procedures to the inner (mucosal) aspect of the lower lip may occasionally cause numbness of the overlying skin. This study was designed to find, by means of dissection and computerized three-dimensional reconstruction, why surgical interference with nerve fibres in the deep aspect of the lip can cause neurological deficit in the superficial layers. Thirteen cadaveric lips were examined by dissection under a surgical microscope (9 lips) or serial sectioning and computerized three-dimensional reconstruction (4 lips). Muscle mass, minor labial salivary glands and nerve fibres were identified and traced. Three patterns of mental nerve distribution were seen on dissection and two on computerized reconstruction; these latter corresponded to two of the patterns seen on dissection. Fibres passing close to the labial minor salivary gland mass were seen to travel towards the superficial aspect of the lip, terminating in the dermis. It is clear that there is no safe anatomical space for minor surgical procedures to the inner (mucosal) aspect of the lower lip if avoidance of cutaneous numbness is an important consideration. However, we describe a technique that may minimize the possibility of cutaneous numbness.

Aged↗
PubMed2003

Analysis of prolapse in cardiovascular stents: a constitutive equation for vascular tissue and finite-element modelling.

The effectiveness of a cardiovascular stent depends on many factors, such as its ability to sustain the compression applied by the vessel wall, minimal longitudinal contraction when it is expanded, and its ability to flex when navigating tortuous blood vessels. The long-term reaction of the tissue to the stent is also device dependant; in particular some designs provoke in-stent restenosis (i.e., regrowth of the occlusion around the stent). The mechanism of restenosis is thought to involve injury or damage to the vessel wall due to the high stresses generated around the stent when it expands. Because of this, the deflection of the tissue between the struts of the stent (called prolapse or "draping") has been used as a measure of the potential of a stent to cause restenosis. In this paper, uniaxial and biaxial experiments on human femoral artery and porcine aortic vascular tissue are used to develop a hyperelastic constitive model of vascular tissue suitable for implementation in finite-element analysis. To analyze prolapse, four stent designs (BeStent 2, Medtronic AVE; NIROYAL, Boston Scientific; VELOCITY, Cordis; TETRA, Guidant) were expanded in vitro to determine their repeating-unit dimensions. This geometric data was used to generate a finite element model of the vascular tissue supported within a repeating-unit of the stent. Under a pressure of 450 mm Hg (representing the radial compression of the vessel wall), maximum radial deflection of 0.253 mm, 0.279 mm, 0.348 mm and 0.48 mm were calculated for each of the four stents. Stresses in the vascular wall were highest for the VELOCITY stent. The method is proposed as a way to compare stents relative to their potential for restenosis and as a basis for a biomechanical design of a stent repeating-unit that would minimize restenosis.

Animals↗
PubMed2002

Effect of thiopental, propofol, and etomidate on vincristine toxicity in PC12 cells.

Neurotoxicity is the dose-limiting side-effect of vincristine in cancer therapy. Using the nerve growth factor (NGF)-dependent neurite outgrowth and cell proliferation of the PC12 pheochromocytoma cell line as an in vitro assay, the protective effect of different intravenous anesthetics was assessed. Vincristine (1 nmol/L) significantly decreased the percentage of neurite-forming cells from 68% +/- 9% to 27% +/- 7% within a 3-day incubation period. The longer neurites (> 2 x cell body) in particular proved to be extremely sensitive to vincristine (from 17% +/- 4% to 0% of total neurite-expressing cells). Flow cytometry results revealed an S-phase percentage of 15.85% +/- 3.25% after NGF induction, with vincristine reducing this percentage to 0.68% +/- 0.38%. Reversal of the inhibitory effect of vincristine was noted in the cells treated with thiopental or propofol but not etomidate. Bicuculline partially antagonized the protective effect of thiopental and propofol in both studies. We conclude that thiopental and propofol, but not etomidate, have a protective effect in vincristine-induced neurotoxicity. The protective effect produced by thiopental and propofol is probably secondary to activation of GABAA receptors.

Animals↗