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Biomedical subjects

C W Cheng

Publications and source records attributed to C W Cheng.

At least 19 recordsLinked to original sources
PubMed2005

Dose perturbations due to contrast medium and air in mammosite treatment: an experimental and Monte Carlo study.

In the management of early breast cancer, a partial breast irradiation technique called MammoSite (Proxima Therapeutic Inc., Alpharetta, GA) has been advocated in recent years. In MammoSite, a balloon implanted at the surgical cavity during tumor excision is filled with a radio-opaque solution, and radiation is delivered via a high dose rate brachytherapy source situated at the center of the balloon. Frequently air may be introduced during placement of the balloon and/or injection of the contrast solution into the balloon. The purpose of this work is to quantify as well as to understand dose perturbations due to the presence of a high-Z contrast medium and/or an air bubble with measurements and Monte Carlo calculations. In addition, the measured dose distribution is compared with that obtained from a commercial treatment planning system (Nucletron PLATO system). For a balloon diameter of 42 mm, the dose variation as a function of distance from the balloon surface is measured for various concentrations of a radio-opaque solution (in the range 5%-25% by volume) with a small volume parallel plate ion chamber and a micro-diode detector placed perpendicular to the balloon axis. Monte Carlo simulations are performed to provide a basic understanding of the interaction mechanism and the magnitude of dose perturbation at the interface near balloon surface. Our results show that the radio-opaque concentration produces dose perturbation up to 6%. The dose perturbation occurs mostly within the distances <1 mm from the balloon surface. The Plato system that does not include heterogeneity correction may be sufficient for dose planning at distances > or = 10 mm from the balloon surface for the iodine concentrations used in the MammoSite procedures. The dose enhancement effect near the balloon surface (<1 mm) due to the higher iodine concentration is not correctly predicted by the Plato system. The dose near the balloon surface may be increased by 0.5% per cm3 of air. Monte Carlo simulation suggests that the interface effect (enhanced dose near surface) is primarily due to Compton electrons of short range (<0.5 mm). For more accurate dosimetry in MammoSite delivery, the dose perturbation due to the presence of a radio-opaque contrast medium and air bubbles should be considered in a brachytherapy planning system.

Artifacts↗
PubMed2004

Low dose BCG as adjuvant therapy for superficial bladder cancer and literature review.

BACKGROUND: Bacillus Calmette-Guerin (BCG) at low doses has long been employed as prophylactic and therapeutic treatment for superficial cancer of the urinary bladder, aiming at reducing toxicity while maintaining efficacy. A retrospective review was reported, together with a review of the literature with respect to a low dose BCG regimen. METHODS: Forty-five consecutive patients with superficial bladder cancer (Ta or T1) with one or more of the appropriate criteria (grade above 1, stage above a, size >1 cm, multiple or recurrent), after complete transurethral resection, received 27 mg Connaught strain BCG weekly for 6 weeks. There was no maintenance therapy. Patients were evaluated with urine cytology and cystoscopy. Recurrence, progression and death were analysed. RESULTS: With a median follow up of 14 (range 3-61) months, 24 (53%) of the 45 patients responded to one course of 6 weekly BCG without recurrence. A further group of 13 (29%) patients responded to a second course of BCG on recurrence. Disease progressed in one (2.2%) patient. Two (4.4%) patients died of an unrelated condition. There was no disease specific mortality. Side-effects were common but well tolerated, with only two (4.4%) cases of treatment interruption. CONCLUSIONS: Low dose BCG could be an alternative option of adjuvant therapy for superficial bladder cancer with acceptable toxicity and good compliance.

Adjuvants, Immunologic↗
PubMed2002

Genetic polymorphism of the CYP2E1 gene and susceptibility to Parkinson's disease in Taiwanese.

Cytochrome p450IIE1 (CYP2E1), an ethanol-inducible cytochrome p450 enzyme, is expressed in the basal ganglia and is probably involved in the activation of neurotoxicants, producing free radical metabolites and resulting in oxidative stress. To examine the association between CYP2E1 polymorphism and the risk of Parkinson's disease (PD), we performed a case-control study on a large population of Taiwanese PD patients, focusing especially on early-onset PD patients (onset at, or before, the age of 50). Two hundred and thirty-four PD patients and 251 age- and sex-matched controls were recruited. A much higher frequency of the uncommon c2 allele was seen in our control subjects than in Caucasians (0.23 vs. 0.02). There were no significant differences between PD patients and controls in the distribution of either allelic or genotype frequencies. Our results suggest that CYP2E1 is not a major or independent determinant in the occurrence of PD in Taiwanese.

Age of Onset↗
PubMed2002

Comparison of beam characteristics in intensity modulated radiation therapy (IMRT) and those under normal treatment condition.

In the step-and-shoot delivery of an IMRT plan with a Siemens Primus accelerator, radiation is turned off by desynchronizing the injector while the field parameters are being changed. When the machine is ready again a trigger pulse is sent to the injector to start the beam instantaneously. The objective of this study is to investigate the beam characteristics of the machine operating in the IMRT mode and to study the effect of the Initial Pulse Forming Network (IPEN) on the dark current. The central axis (CAX) output for a 10 x 10 cm2 field over the range 1-100 MU was measured with an ion chamber in a polystyrene phantom for both 6 and 15 MV x rays. Beam profiles were also measured over the range of 2-40 MU with the machine operating in the IMRT mode and compared with those in the normal mode. By adjusting the IPFN value, dark current radiation (DCR) was measured using ion chamber measurements. For both the normal and IMRT modes, dose versus MU is nonlinear in the range 1-5 MUs. Above 5 MU, dose varies linearly with MU for both 6 and 15 MV x rays. For stability of dose profiles, the 2 MU-IM group exhibit 20% variation from one subfield to another. The variation is about 5% for the 8 MU-IM group and <5% for 10 MU and higher. The results are similar in the normal treatment mode. With the IPFN at >80% of the PFN value, a spurious radiation associated with dark current at approximately 0.7% of the dose at isocenter for a 10 x 10 cm2 field is detected during the "PAUSE" state of the accelerator for 15 MV x rays. When the IPFN is lowered to <80% of the PFN value, no DCR is detected. For 6 MV x rays, no measurable DCR was detected regardless of the IPFN setting.

Humans↗
PubMed2001

Role of multileaf collimator in replacing shielding blocks in radiation therapy.

To facilitate the use of multileaf collimator (MLC) in field shaping, we tested the hypothesis that the changes in the penumbra due to MLC replacing a Cerrobend block can be related to a change in the margin of the block. We also investigated if it is possible to estimate the effect of MLC replacing a block in terms of a change in the block margin. Calculations were performed for a single field as well as a multiple field setup. For the single field setup, blocks with equal areas were drawn at the four corners of a 16 x 20 cm(2) field at angles of 20 degrees, 40 degrees, 60 degrees, and 80 degrees with the horizontal axis. The blocks were then replaced with MLC leaves. For 6 MV x-rays, dose profiles in the penumbra regions of the blocks at 5- and 10-cm depths were compared with those obtained with the corresponding MLC setup. For multiple fields, the same sets of blocks were set up on the anterio-posterior (AP-PA) pair of a four-field setup. The margins of the blocks were increased (i.e., block shaved) in 1 mm steps to a maximum of 6 mm. The similarity between MLC and the change in the block margin was examined by comparing the dose-volume histogram (DVH) of the normal tissues in the penumbral regions for the different setups. To correlate the effect of MLC with a change in the block margin, difference dose-volume histograms (DDVH) of the normal tissues relative to the original block were compared for the MLC setup with those for the changes in the block margin. The correlation obtained was used to predict the effect on the penumbra region of the MLC setup for the lateral fields of a patient irradiated with a four-field setup. The calculations were carried out with 15 MV x-rays. For the single field setup, dose undulation is largest for the 50% isodose line (IDL) as reflected in the largest increase in the 50% to 20% isodose region compared with the 90% to 10% and the 80% to 20% regions. The increase in the penumbral width is largest for the 20 degrees block when replaced by the MLC and is smaller as the angle increases. The increase in the penumbral width also increases with depth. The effect of replacing a Cerrobend block with an MLC is similar to an increase in the block margin. For 15 MV x-rays, the increase varies inversely with the angle of the blocks, from > 6 mm increase in block margin for the 20 degrees block to about 1 mm for the 80 degrees block. In the clinical example, replacing the blocks in the lateral fields of a four-field irradiation with MLC is similar to changing the margin of the blocks. For the posterior block, MLC is similar to a 1- to 2-mm increase in the margin of the block, whereas for the anterior block the effect is similar to 1 mm for the straight portion of the block to about 6 mm in the superior portion of the block. Characterization of an MLC setup replacing a Cerrobend block is necessary for adequate coverage of target volume. The effect of MLC replacing a Cerrobend block is similar to a change in the block margin. It is possible to estimate with reasonable accuracy the effect of MLC replacing a Cerrobend block.

Humans↗
PubMed2001

Mechanisms of inactivation of E-cadherin in breast carcinoma: modification of the two-hit hypothesis of tumor suppressor gene.

Loss of heterozygosity (LOH) allows the expression of recessive mutation in tumor suppressor genes (TSG). Therefore, on the basis of Knudson's 'two-hit' hypothesis for TSG inactivation, the detection of a high LOH frequency in a chromosomal region is considered critical for TSG localization. One of these LOH regions in breast cancer is 16q22.1, which has been suggested to reflect the involvement of E-cadherin (E-cad), a cell-cell adhesion molecule. To confirm the tumorigenic role of E-cad, 81 sporadic invasive ductal carcinomas (IDCs) of the breast were tested for the 'two hits' required to inactivate this gene. A high frequency (37.3%) of LOH was detected in 67 informative tumors, but no mutation was found. To examine the possibility that transcriptional mechanisms serve as the second hit in tumors with LOH, specific pathways, including genetic variant and hypermethylation at the promoter region and abnormal expression of positive (WT1) and negative (Snail) transcription factors, were identified. Of these, promoter hypermethylation and increased expression of Snail were found to be common (>35%), and to be strongly associated with reduced/negative E-cad expression (P<0.05). However, unexpectedly, a significantly negative association was found between the existence of LOH and promoter hypermethylation (P<0.05), which contradicts the 'two-hit' model. Instead, since they coexisted in a high frequency of tumors, hypermethylation may work in concert with increased Snail to inactivate E-cad expression. Given that E-cad is involved in diverse mechanisms, loss of which is beneficial for tumors to invade but may also trigger apoptosis, this study suggests that maintaining a reversible mechanism, either by controlling the gene at the transcriptional level or by retaining an intact allele subsequent to LOH, might be important for E-cad in IDC and may also be common in TSGs possessing diverse functions. These findings provide clues to explain why certain TSGs identified by LOH cannot fulfil the two-hit hypothesis.

Adaptor Proteins, Signal Transducing↗
PubMed2001

The COMT L allele modifies the association between MAOB polymorphism and PD in Taiwanese.

OBJECTIVE: Reports suggest that catechol-O-methyltransferase (COMT(L/L)) (Val(158)/Met) and monoamine oxidase B (MAOB) intron 13 genotype polymorphism is associated with PD. To understand the ethnicity-specific effects of genetic polymorphism, we performed a case-control study of the association between PD susceptibility and polymorphism of MAOB and COMT, both separately and in combination, in Taiwanese. METHODS: Two hundred twenty-four patients with PD and 197 controls, matched for age, sex, and birthplace, were recruited. MAOB and COMT polymorphism genotyping was performed by using PCR-based restriction fragment length polymorphism (RFLP) analyses. chi(2), OR, and Fisher's exact tests were used to compare differences in allelic frequencies and genotypes. RESULTS: The MAOB G genotype (G in men and G:/G in women) was associated with a 2.07-fold increased relative risk of PD. COMT polymorphism, considered alone, showed no correlation with PD risk; however, a significant synergistic enhancement was found in PD patients harboring both the COMT(L) and MAOB G genotypes. CONCLUSIONS: These results suggest that, in Taiwanese, PD risk is associated with MAOB G intron 13 polymorphism, and this association is augmented in the presence of the COMT(L) genotype, indicating an interaction of these two dopamine-metabolizing enzymes in the pathogenesis of sporadic PD. However, the relatively low frequencies of these combined genotypes in our study necessitates confirmation with a larger sample size.

Aged↗
PubMed2001

Determination of urine catecholamines by capillary electrophoresis with dual-electrode amperometric detection.

Demonstrated in this study is that without pretreatment and preconcentration nanomolar-level catecholamines in human urine samples can be quantitatively determined with ease by utilizing capillary electrophoresis coupled with amperometric detection. The detector employs a parallel-opposed dual-electrode scheme assembled with an on-capillary electrode and a disk electrode and takes advantage of the redox cycling of analytes between the two working electrodes to improve the limit of detection. The matrix effect of urine samples significantly decreases the detection sensitivity from that obtained in standard solutions. Therefore, calibration curves derived from standard solutions cannot be used in quantitative determination of catecholamines. Methods of standard addition and internal standard have been studied. The results suggest that isoproterenol is a good internal standard to facilitate the measurements of dopamine, epinephrine, and norepinephrine in human urine samples.

Catecholamines↗
PubMed2001

Identification and expression of zebrafish Iroquois homeobox gene irx1.

Iroquois homeoproteins are prepatterning factors that positively regulate proneural genes and control neurogenesis. We have identified a zebrafish Iroquois gene, irx1, which is highly homologous to Xenopus Xiro1, Gallus c-Irx1 and mouse Irx1. Expression of irx1 was initially detected at the bud stage. By 16 h post-fertilization (hpf), irx1 expression was exclusively limited to the prospective midbrain and hindbrain. By 24 hpf, irx1 expression was clearly detected in the acousticovestibual ganglia, tectum, tegmentum, cerebellum and rhombomere 1 but not in rhombomere 2 or mid-hindbrain boundary.

Amino Acid Sequence↗
PubMed2001

Spectrum of prostate cancer in the Singapore General Hospital (1980 to 1985).

INTRODUCTION: Serum prostate specific antigen (PSA) testing has contributed to a dramatic rise in the incidence of prostate cancer diagnosed in the last decade in the West as well as in Singapore. Now prostate cancer is ranked as the sixth commonest cancer among men in Singapore. To form the basis for comparisons and to assess the trends and impact of these changes, we analysed the presentation, disease characteristics and outcome of treatment of patients with prostate cancer diagnosed in the pre-PSA era at the Singapore General Hospital (SGH). MATERIALS AND METHODS: Of the 149 patients (1980 to 1985) registered in the database, 134 (90%) records with full follow-up data were available for the analysis. All patients were diagnosed and managed at SGH. Follow-up and death data were collected through clinic visit, phone interviews of the patients, relatives, family physicians and the death registry. Survival analysis was carried out using the Kaplan-Meier product limit method. RESULTS: The mean age at diagnosis was 69.8 years. There were no significant changes with reference to each year during 1980 to 1985 and the mean number of diagnoses per year was 22.3. Of the 134 patients, 86% had either retention of urine or severe lower urinary tract symptoms and 14% had metastatic disease at presentation. Most histological diagnosis was made during prostatectomy; wherein 82% was found with transurethral resection of the prostate (TURP) and 12% in open prostatectomy, respectively. Pathological analysis during diagnosis revealed that 72.4% patients had metastatic disease. Of which, 57.5% had high-grade (Gleason > 7) tumours. Among these, 82% underwent TURP to relieve urinary obstruction, while 26.1% received local irradiation to the prostate. Majority had hormone therapy shortly after diagnosis in the form of orchidectomy or oral diethylstilbestrol (76.1%). The median crude survival (26 months) was minimal for metastatic patients. CONCLUSION: The spectrum of prostate cancer in the pre-PSA era was characterised by high stages of high-grade disease, with very limited opportunity for successful treatment and hence survival.

Aged↗
PubMed2001

Acute renal colic: value of unenhanced spiral computed tomography compared with intravenous urography.

OBJECTIVE: The objective of this study was to compare the efficacy of plain spiral computed tomographic (CT) scan with intravenous urography (IVU) in the evaluation of patients with suspected urinary calculi/obstruction. MATERIALS AND METHODS: Twenty consecutive patients with acute signs of renal colic were prospectively examined with unenhanced spiral CT followed by an IVU within the same day. The CT scans were reviewed jointly by 2 radiologists blinded to the IVU and a consensus was reached for each finding. The IVU was similarly reviewed by another 2 separate radiologists. RESULTS: Eleven of the 20 patients had signs of urinary obstruction on CT and IVU. Of these 11 patients, 7 had a ureteric calculus that was demonstrated on CT and IVU and 4 had a calculus that was demonstrated on CT only. Two patients had a urinary calculus seen on CT and IVU with no signs of urinary obstruction. One patient had a calculus seen on CT alone with no urinary obstruction. Two patients only had signs of urinary obstruction on CT. The remaining 4 cases had normal findings on CT and IVU. CONCLUSION: Unenhanced CT is more effective than IVU in identifying ureteric calculi and is equally effective in detecting urinary obstruction. CT is also useful in detecting secondary signs of obstruction even in the absence of any calculus.

Acute Disease↗
PubMed2000

Expression of two novel mouse Iroquois homeobox genes during neurogenesis.

Members of the Drosophila Iroquois homeobox gene family are implicated in the development of peripheral nervous system and the regionalization of wing and eye imaginal discs. Recent studies suggest that Xenopus Iroquois homeobox (Irx) genes are also involved in neurogenesis. Three mouse Irx genes, Irx1, Irx2 and Irx3, have been previously identified and are expressed with distinct spatio-temporal patterns during neurogenesis. We report here the cloning and expression analysis of two novel mouse Irx genes, Irx5 and Irx6. Although Irx5 and Irx6 proteins are structurally more related to one another, we find that Irx5 displays a developmental expression pattern strikingly similar to that of Irx3, whereas Irx6 expression resembles that of Irx1. Consistent with the notion that Mash1 is a putative target gene of the Irx proteins, all four Irx genes display an overlapping expression pattern with Mash1 in the developing CNS. In contrast, the Irx genes and Mash1 are expressed in complementary domains in the developing eye and olfactory epithelium.

Amino Acid Sequence↗
PubMed2000

A histomorphometric observation of flows in cortical bone under dynamic loading.

Ferritin was used as a histological marker for interstitial fluid flows in four goats. Two transcortical pins were inserted into each tibia mediolaterally-one at the proximal side and one at the distal side of the diaphysis. For the experimental limb, dynamic loading was applied to the pins on the lateral side. The contralateral limb was used as control. Ferritin was injected into the nutrient arteries feeding the two tibiae. The goat was then euthanized immediately. Undecalcified slides of the tibial cortical bone from both the experimental and the control limbs were studied histologically. Percentages of Haversian systems marked with ferritin halos and the average radial distance of ferritin transudation away from the Haversian canals were assessed. Results for the medial and lateral sides of both the experimental and control tibiae were reported. Significant differences in the ferritin transudation distance were found between the experimental and the control tibia (P < 0.005) and between the medial and the lateral sectors (P < 0.05). The approach documented in this paper could be used to address systematically how external loading might affect the transport phenomena in cortical bone.

Animals↗
PubMed2000

Zinc and nitric oxide synthase inhibitor L-NAME attenuate NPY-induced feeding in mice.

The influences of zinc (Zn) and the nitric oxide synthase (NOS) inhibitor L-NAME on peripheral neuropeptide Y (NPY)-induced feeding in mice were investigated. Male mice received NPY (200 ng/d/mouse subcutaneously) and were separated into four groups based on cotreatments (with or without Zn [0.1 mg/mL]) and with or without L-NAME [0.2 mg/mL]) administered in drinking water for 10 d. A control group that received saline injection was also studied. The results showed that NPY, with or without any studied chemicals, did not affect body weight gain or body fat content. However, the mice that were administered NPY alone had increased energy intakes, higher serum triglyceride and free fatty acid, and lower serum glucose than saline-injected controls. NPY-treated mice that were given Zn and L-NAME cotreatments had compatible results of determined variables in comparison with control mice. This study showed that Zn and L-NAME attenuated NPY-mediated feeding and selected serum variables in mice. However, the mechanisms of the interactions among NPY, Zn and NOS, and their effects on appetite regulation, remain to be elucidated.

Animals↗
PubMed2000

Cystoscopic diagnosis of bladder cancer by intravesical instillation of 5-aminolevulinic acid induced porphyrin fluorescence--the Singapore experience.

OBJECTIVES: 1) To determine whether fluorescence cystoscopy after intravesical administration of 5-aminolevulinic acid (5-ALA) is more sensitive in detection of dysplasia and bladder cancer when compared with conventional cystoscopy. 2) To determine the safety of using 5-ALA. MATERIALS AND METHODS: A 3% 5-ALA solution was instilled intravesically before cystoscopy in 41 patients. The 5-ALA-induced porphyrin fluorescence was excited by violet light from a xenon arc lamp (lambda 375-440 mm). RESULTS: Among the 175 biopsies obtained, the sensitivity of the fluorescence cystoscopy was greater than that of conventional cystoscopy (89.1% versus 65.6%, P < 0.05). Specificity was at 64.8% and 83.8% respectively with P < 0.05. Duration of ALA instillation did not seem to affect the sensitivity and specificity of photodynamic diagnosis. The procedures were well tolerated by all patients with no additional complication. CONCLUSIONS: Fluorescence-guided biopsies are more sensitive than random biopsies in detecting dysplasia or bladder cancer without additional risk or complication. The duration of ALA instillation did not seem to affect the accuracy of photodynamic diagnosis.

Administration, Intravesical↗
PubMed2000

Six-year follow-up of untreated T1 carcinoma of prostate.

INTRODUCTION: The management of T1 carcinoma of prostate remains controversial and the critical role of histopathology is often underestimated. MATERIALS AND METHODS: A retrospective review was conducted on 27 cases of T1 prostate carcinoma diagnosed between 1980 and 1992, all of which were managed on a surveillance programme. Pathological material of 24 cases was available for re-examination by a single histopathologist without prior knowledge of the originally assigned grade. Gleason's scoring system was used in the current review. RESULTS: Twenty-two (81.5%) were T1a and 5 (18.5%) T1b. Mean duration of follow-up was 77.3 months (1.0 to 159.0) and median age was 72.0 years (61.0 to 84.0). Twenty-five (92.6%) were originally graded as well differentiated, 1 (3.7%) was moderately differentiated and 1 (3.7%) was poorly differentiated. Three of the well-differentiated tumours were upstaged because of tumour volume. On review, differences in grading were noted in 13 cases (54.2%) and 11 (45.8%) were, as a consequence, upstaged. Progression was recorded in 5 cases (18.5%). Mean disease-free interval was 47.6 months (7.0 to 75.0) and mean serum PSA at progression was 34.2 ug/l (2.3 to 62.5). Four responded to delayed therapy. Mortality was recorded in 13 cases (48.1%) but cancer-specific mortality was only 7.7% (1/13). Mean age at death was 78.1 years. CONCLUSION: The importance of accurate grading and staging cannot be overemphasized given its pivotal role in subsequent management. The impact of age is also apparent and surveillance appears a reasonable option for those with limited life expectancy after diagnosis.

Adenocarcinoma↗