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Biomedical subjects

James Chu

Publications and source records attributed to James Chu.

10 recordsLinked to original sources

Surface optimization technique for MammoSite breast brachytherapy applicator.

PURPOSE: We present a technique to optimize the dwell times and positions of a high-dose-rate (192)Ir source using the MammoSite breast brachytherapy applicator. The surface optimization method used multiple dwell positions and optimization points to conform the 100% isodose line to the surface of the planning target volume (PTV). METHODS AND MATERIALS: The study population consisted of 20 patients treated using the MammoSite device between October 2002 and February 2004. Treatment was delivered in 10 fractions of 3.4 Gy/fraction, twice daily, with a minimum of 6 h between fractions. The treatment of each patient was planned using three optimization techniques. The dosimetric characteristics of the single-point, six-point, and surface optimization techniques were compared. RESULTS: The surface optimization technique increased the PTV coverage compared with the single- and six-point methods (mean percentage of PTV receiving 100% of the prescription dose was 94%, 85%, and 91%, respectively). The surface method, single-point, and six-point method had a mean dose homogeneity index of 0.62, 0.68, and 0.63 and a mean full width at half maximum value of 189, 190, and 192 cGy/fraction, respectively. CONCLUSION: The surface technique provided greater coverage of the PTV than did the single- and six-point methods. Using the FWHM method, the surface, single-, and six-point techniques resulted in equivalent dose homogeneity.

Brachytherapy↗

The MammoSite breast brachytherapy applicator: a review of technique and outcomes.

The MammoSite breast brachytherapy device was designed to overcome the potential scheduling problems associated with external beam radiotherapy (EBRT) and the technical difficulties of multi-catheter-based interstitial brachytherapy. The device consists of a silicone balloon connected to a catheter which contains an inflation channel and a port for passage of a high-dose-rate brachytherapy source. The American Brachytherapy Society and American Society of Breast Surgeons have published partial breast irradiation (PBI) patient selection guidelines. The MammoSite applicator has been shown in two dosimetric studies to treat a comparable volume to multicatheter-based interstitial implants. The MammoSite catheter can be placed at the time of lumpectomy or in a separate procedure using ultrasound guidance. Four optimization methods have been described: the single point method, the six prescription point method (RUSH Technique), the University of Southern California Norris Cancer Center Method, and the Surface Optimization Technique. An excellent or good cosmetic outcome has been reported in 80% to 93% of patients at 1 year in most studies. Cosmetic results appear highly related to skin spacing. The MammoSite applicator has been associated with early side effects comparable with traditional breast conserving therapy. A NSABP trial will randomize patients to either whole breast irradiation or PBI consisting of interstitial brachytherapy, MammoSite brachytherapy, or 3D conformal radiation.

Brachytherapy↗

Treatment volume and dose optimization of MammoSite breast brachytherapy applicator.

PURPOSE: Limited information has been reported on the dosimetry achieved with the MammoSite breast brachytherapy applicator. We present our results regarding the volume of treatment and a comparison of a single prescription point, single dwell position optimization technique with a six prescription point, multiple dwell position method. METHODS AND MATERIALS: Between October 14, 2002 and February 28, 2003, 21 patients with early-stage breast cancer were treated using the MammoSite device. The treatment was delivered in 10 fractions of 3.4 Gy/fraction, b.i.d., with a minimum of 6 hours between the daily fractions. CT of the lumpectomy cavity was obtained both with and without the inflated balloon. A planning target volume was constructed using a three-dimensional planning system. A three-dimensional expansion of the balloon surface was performed using the chest wall and skin as limiting structures. The volume of the inflated balloon was removed from this volume, and the volume of tissue treated in each patient was determined. A sequential expansion in 1-mm increments around the empty lumpectomy cavity was performed until the closest equivalent volume to the planning target volume was obtained. The treatment for the patients in this study was planned using both a single prescription point, single dwell position optimization technique and a six-prescription point, multiple dwell position technique. The single prescription point method has been described in a previous publication. The six-prescription point method used six points placed 1 cm from the balloon surface. Four points are in a plane transverse to the balloon axis perpendicular to the axis of the catheter, and two points are placed along the axis of the catheter. The prescription points along the catheter axis are used to compensate for the decreased dose coverage owing to anisotropy dose distribution of the source. The Nucletron HDR Plato Brachytherapy planning system was used to optimize the source positions and dwell times. RESULTS: The volume of breast tissue treated by the MammoSite device was equal to the volume encompassed by a mean 1.6-cm (SD, 0.1) margin around the empty lumpectomy cavity. Compared with the single prescription point optimization method, the six prescription point method provided better dose coverage, with a mean percentage of volume receiving 90% of the prescription dose of 97.2% (SD = 2.1) vs. 89.5% (SD = 4.6) for the single-point method. The mean percentage of volume receiving 100% of the prescription dose was 88.9% (SD = 3.3) for the six-point method vs. 77.6% (SD = 6.1) for the single-point method. However, compared with the single-point method, the six-point optimization method resulted in treatment that was less uniform, with a mean dose homogeneity index of 0.62 (SD =.07) vs. 0.66 (SD =.08) for the single-point method. CONCLUSION: The volume of normal breast tissue treated by the MammoSite device is comparable to other methods of interstitial brachytherapy that treat a 1-2-cm margin of tissue around the excision cavity. The six-prescription point, multiple dwell position method improved dose coverage with a slight decrease in dose homogeneity. The six-point method offers greater reliability of dose coverage compared with the single-point method by providing an increased number of reference points.

Adult↗

The effect of silica-containing calcium-phosphate particles on human osteoblasts in vitro.

There is an ongoing need for more effective and less costly bone substitutes. It has previously been proposed that silica-containing bioactive glass would be more effective as a bone repair material because of its physiochemical properties. Three newly synthesized silica-containing bioactive glass formulations, HA-31 (25%), HA-11 (50%), and HA-13 (75%), were tested as biocompatible substrates for the continued proliferation and phenotype expression of human bone cells in vitro. Two currently available bioactive glasses (BioGlass(R), Hydroxyapatite) served as comparisons. The biocompatibility of these bioglasses, as well as their osteoconductive properties, was assessed by employing primary cultures of human osteoblasts and human synoviocytes for 4 days. The results obtained demonstrated that the three new bioglasses enhanced the proliferative response of osteoblasts compared with osteoblasts cultured alone. Reverse Transcription Polymerase Chain Reaction (RT-PCR) analysis indicated that osteoblasts retained their phenotypic expression by continued expression of collagen type I and alkaline phosphatase. The newly synthesized preparations of silica-containing bioactive glass did not induce stimulation of proinflammatory markers iNOS and IL-1beta in synoviocytes. In conclusion, the newly synthesized silica-containing bioactive glasses are biocompatible substrate for bone-forming osteoblasts. However, the formulations tested did not show significant advantage over the currently available bioactive glasses in vitro.

Alkaline Phosphatase↗

Use of metabolic markers to identify overweight individuals who are insulin resistant.

BACKGROUND: Insulin resistance is more common in overweight individuals and is associated with increased risk for type 2 diabetes mellitus and cardiovascular disease. Given the current epidemic of obesity and the fact that lifestyle interventions, such as weight loss and exercise, decrease insulin resistance, a relatively simple means to identify overweight individuals who are insulin resistant would be clinically useful. OBJECTIVE: To evaluate the ability of metabolic markers associated with insulin resistance and increased risk for cardiovascular disease to identify the subset of overweight individuals who are insulin resistant. DESIGN: Cross-sectional study. SETTING: General clinical research center. PATIENTS: 258 nondiabetic, overweight volunteers. MEASUREMENTS: Body mass index; fasting glucose, insulin, lipid and lipoprotein concentrations; and insulin-mediated glucose disposal as quantified by the steady-state plasma glucose concentration during the insulin suppression test. Overweight was defined as body mass index of 25 kg/m2 or greater, and insulin resistance was defined as being in the top tertile of steady-state plasma glucose concentrations. Receiver-operating characteristic curve analysis was used to identify the best markers of insulin resistance; optimal cut-points were identified and analyzed for predictive power. RESULTS: Plasma triglyceride concentration, ratio of triglyceride to high-density lipoprotein cholesterol concentrations, and insulin concentration were the most useful metabolic markers in identifying insulin-resistant individuals. The optimal cut-points were 1.47 mmol/L (130 mg/dL) for triglyceride, 1.8 in SI units (3.0 in traditional units) for the triglyceride-high-density lipoprotein cholesterol ratio, and 109 pmol/L for insulin. Respective sensitivity and specificity for these cut-points were 67%, 64%, and 57% and 71%, 68%, and 85%. Their ability to identify insulin-resistant individuals was similar to the ability of the criteria proposed by the Adult Treatment Panel III to diagnose the metabolic syndrome (sensitivity, 52%, and specificity, 85%). CONCLUSIONS: Three relatively simple metabolic markers can help identify overweight individuals who are sufficiently insulin resistant to be at increased risk for various adverse outcomes. In the absence of a standardized insulin assay, we suggest that the most practical approach to identify overweight individuals who are insulin resistant is to use the cut-points for either triglyceride concentration or the triglyceride-high-density lipoprotein cholesterol concentration ratio.

Adult↗

Three-dimensional photon dosimetry: a comparison of treatment of the intact breast in the supine and prone position.

PURPOSE: To compare the adequacy of target coverage, dose homogeneity, and volume of normal tissue irradiated in treatment of the intact breast in the supine and prone position. METHODS AND MATERIALS: Fifteen patients with early breast cancer who presented for treatment to the intact breast after excisional biopsy were studied. A specially designed device was used for the prone setup to displace the contralateral breast away from the tangential field borders. Treatment planning computed tomography was performed for each patient in both the supine and prone positions. Dosimetric data were obtained in both positions and isodose distributions were calculated for each patient in both positions. RESULTS: The volume of breast receiving greater than 5% of the prescribed dose was significantly less in the prone position. Medial wedges were either not used or their angles were reduced for all patients in the prone position compared with the supine position. The average volume of lung receiving >10 Gy and >20 Gy was significantly less in the prone positions. The volume of heart irradiated at critical dose levels did not vary consistently in the prone and supine positions. The integral dose delivered to the contralateral breast was not significantly different. CONCLUSION: Treatment of the intact breast in the prone position may result in improved dose homogeneity within the target volume as well as sparing of normal lung compared with treatment in the conventional supine position.

Adult↗

Quantification of insulin-mediated glucose disposal in HIV-infected individuals: comparison of patients treated and untreated with protease inhibitors.

To describe the distribution of insulin sensitivity and glucose tolerance in HIV-infected patients, the authors measured insulin-mediated glucose disposal (IMGD) in 51 subjects (24 protease inhibitor (PI)-treated subjects and 27 non-PI-treated subjects). IMGD was determined by measuring the steady-state plasma glucose (SSPG) concentration during the last 30 minutes of a 180-minute intravenous infusion of octreotide, glucose, and insulin. In addition, oral glucose tolerance testing was performed. SSPG concentrations varied six-fold in both groups, and the mean values +/- SEM did not differ between PI-treated and non-PI-treated groups (8.7 +/- 0.9 vs. 8.0 +/- 0.7 mmol/L, respectively). The mean fasting plasma glucose concentration +/- SEM was higher in the PI-treated subjects than in the non-PI-treated subjects (5.44 +/- 0.11 vs. 5.05 +/- 0.11 mmol/L, respectively; p =.01), whereas fasting plasma insulin concentrations did not differ. PI-treated patients also had significantly higher plasma glucose (p =.001) and insulin (p =.03) responses to the oral glucose challenge. However, whereas the incremental plasma glucose response during the first 30 minutes was significantly higher in PI-treated patients, the incremental insulin response in the two groups was identical. In conclusion, insulin sensitivity varies widely in HIV-infected patients irrespective of PI treatment, and the adverse effect of PIs on insulin sensitivity is likely to be of modest magnitude. Finally, PI treatment may have an inhibitory effect on insulin secretion.

Adult↗

Cosmetic outcome and incidence of infection with the MammoSite breast brachytherapy applicator.

We present our results regarding the cosmetic outcome achieved and the rate of infection using the MammoSite breast brachytherapy applicator to treat patients with partial breast irradiation. In addition, factors associated with cosmetic outcome and infection are analyzed. The study population consisted of 30 patients with early stage breast cancer treated using the MammoSite device from October 28, 2002, to February 13, 2004. Cosmetic outcome was analyzed for its association with the following parameters: volume of the balloon, balloon-to-skin distance, maximal skin point dose per fraction, V100 (percent of volume that received 100% of the prescription dose), V150 (percent of volume that received 150% of the prescription dose), and V200 (percent of volume that received 200% of the prescription dose). The occurrence of infection at the time of treatment and during follow-up was also recorded. At a median follow-up of 13 months (range 1-16 months), 53.3% of the patients (16/30) were reported to have an excellent cosmetic outcome and 40.0% (12/30) had a good cosmetic outcome. Excellent cosmetic outcome was associated with a greater mean balloon-to-skin distance compared to those who achieved a good cosmetic outcome (1.5 cm versus 1.2 cm) (p = 0.164). The mean V100, V150, and V200 of those in the excellent cosmetic outcome group were 92.1%, 34.5%, and 7.6% versus 93.0%, 34.7%, and 7.6% in the good cosmetic outcome group (p = 0.642, 0.926, and 0.853), The mean balloon volumes were 47.7 cm3 and 56.9 cm3, respectively (p = 0.063) in the excellent and good outcome groups. The mean maximal skin doses per fraction in the excellent and good outcome groups were 354.8 cGy and 422.3 cGy (p = 0.286), respectively. Infection occurred in 13.3% of the patients (4/30). An excellent or good cosmetic outcome was achieved in 93.3% of patients and infection occurred in 13.3% of patients treated with the MammoSite breast brachytherapy applicator. Excellent cosmetic outcome was associated with a greater balloon-to-skin distance, lower maximal skin dose per fraction, and smaller mean balloon volume; however, the results did not reach statistical significance.

Adult↗

Relative effects of insulin resistance and protease inhibitor treatment on lipid and lipoprotein metabolism in HIV-infected patients.

BACKGROUND: The relationship between insulin resistance, dyslipidemia, HIV infection, and antiretroviral therapy remains unclear, and the atherogenic nature of lipid and lipoprotein profiles in HIV-infected patients has not been fully characterized. METHOD: We measured plasma lipid and lipoprotein subfractions using Vertical Auto Profile-II methodology and directly measured insulin-mediated glucose disposal in 45 protease inhibitor (PI)-treated and non-PI-treated HIV-infected patients. RESULTS: PI-treated patients had higher total, LDL, and narrow-density LDL cholesterol (p <.05) and a trend toward higher triglycerides, whereas HDL cholesterol and LDL particle characteristics were unrelated to PI use or history of lipodystrophy. Insulin sensitivity did not differ on the basis of PI therapy, but decreased insulin sensitivity was associated with lower HDL and HDL-3 cholesterol (p <.01); elevated triglyceride (p <.01), VLDL 1+2, and VLDL 3a+3b lipoproteins (p <.01); and smaller, denser (more atherogenic) LDL particle characteristics (p <.01). Thus, the lipoprotein abnormality associated with PI use was increased LDL cholesterol, whereas changes in TG and HDL metabolism were associated with insulin resistance, independent of PI use. CONCLUSION: The variables of PI-treatment, dyslipidemia, lipodsytrophy, and insulin resistance do not always cluster together in HIV-infected patients, which suggests that the metabolic phenotype emerging in treated patients results from a complex interplay of drug effects, immune restoration, and baseline insulin sensitivity.

Adult↗