Biomedical subjects

Lei Dong

Publications and source records attributed to Lei Dong.

At least 73 records · Page 4Linked to original sources

PubMed2004

Composite score of reflux symptoms in diagnosis of gastroesophageal reflux disease.

AIM: To evaluate the significance of the composite score of reflux symptoms in the diagnosis of gastroesophageal reflux disease (GERD), and to determine the relationship of the composite score with reflux esophagitis (RE) and pathological gastroesophageal reflux (PGER). METHODS: Upper digestive endoscopy and /or 24-h esophageal pH monitoring were performed in 244 subjects. Of these, 54 were consecutive patients attending our clinic with symptoms suggestive of GERD, and 190 were randomly selected from 2532 respondents who participated in our previous general population-based study on GERD. A standardized questionnaire was used to classify both the frequency and severity of typical symptoms of GERD (heartburn, acid and food regurgitation) using a 4-score scale, and the composite score of main reflux symptoms (score index: SI, range from 0 to 18) were calculated for every subject. RE was diagnosed according to the Savary-Miller criteria. Subjects with abnormal pH-metry (DeMeester score more than 14.7) were considered to have PGER. GERD patients were defined as the subjects with RE and/or PGER. RESULTS: The sensitivity of SI in the diagnosis of GERD was inversely associated with SI, but the specificity tended to increase with increased SI. With the cut-off of 8, the SI achieved the highest accuracy of 70.0%, with a sensitivity of 78.6% and a specificity of 69.2% in diagnosing GERD, followed by the cut-off of 3, which had an accuracy of 62.1%, a sensitivity of 96.4% and a specificity of 34.6%. The prevalence of RE, PGER and GERD was strongly associated with increased SI (P<0.01), but there was no significant association between the severity of RE and SI (P>0.05). Among patients with RE, 69.2% had PGER, and 30.8% were confirmed to have negative findings of pH monitoring. Among patients with PGER, 52.9% were identified to have RE and 47.1% had negative endscopic findings in esophagus. CONCLUSION: According to the composite score of main reflux symptoms, the diagnosis of GERD can be made without further tests in most cases. However, 24-h esophageal pH monitoring and upper digestive endoscopy are still indicated in patients with mild and atypical symptoms.

Adult↗

PubMed2004

Effects of motilin and ursodeoxycholic acid on gastrointestinal myoelectric activity of different origins in fasted rats.

AIM: To investigate gastrointestinal migrating myoelectric complex (MMC) and the effects of porcine motilin and ursodeoxycholic acid (UDCA) on MMC of gastrointestinal tract of different origins in fasted rats. METHODS: Three bipolar silver electrodes were chronically implanted on the antrum, duodenum and jejunum. Seven days later 24 experimental rats were divided into 2 groups. One group was injected with porcine motilin via sublingual vein at a dose of 20 microg/kg, the other group was perfused into stomach with UDCA. The gastrointestinal myoelectric activity was recorded 1 h before and 2 h after the test substance infusions into the rats. RESULTS: In all fasted rats a typical pattern of MMC was observed. Among the totally 68 activity fronts recorded in fasted rats under control, 67% started in duodenum, and 33% in antrum. MMC cycle duration and duration of phase III of antral origin were longer than those of duodenal origin. Administration of 20 microg/kg porcine motilin induced a premature antral phase III of antral origin. But perfusion into stomach with UDCA resulted in shorter MMC cycle duration, longer duration of phase III of duodenal origin, which were followed with shorter cycle duration and duration of antral phase III. CONCLUSION: In fasted rats, MMC could originate from antrum and duodenum respectively. The characteristics of MMC of different origins may contribute to the large variations within subjects. The mechanisms of different origins of phase III may be different. Porcine motilin and UDCA could affect MMC of different origins of the gastrointestinal tract in fasted state, respectively.

Animals↗

PubMed2004

Antibacterial prenylflavone derivatives from Psoralea corylifolia, and their structure-activity relationship study.

Three new prenylflavonoids, namely corylifols A-C (1-3), together with 13 known ones, were isolated from the seeds of Psoralea corylifolia. Their structures were elucidated by spectral methods including 1D and 2D NMR techniques. All the isolates were tested on antibacterial assays, and nine of them showed significant antibacterial activities against two pathogenic bacteria Staphylococcus aureus and S. epidermidis. The antibacterial structure-activity relationship of these prenylflavonoids (1-16) was also briefly discussed.

Anti-Bacterial Agents↗

PubMed2004

Cluster models of dose-volume effects.

PURPOSE: Describe cluster models, normal-tissue complication probability models in which both the number and the spatial location of radiation-sterilized functional subunits play a role in defining complication probability. METHODS AND MATERIALS: Computer simulation was used to determine the maximum size cluster of sterilized subunits associated with a given dose distribution. Complications were associated with large clusters. RESULTS: Cluster models showed a volume effect, as increasing effect for constant dose when the volume increased or constant effect when the dose was reduced with increasing volume. Cluster models gave similar results to existing models when tissues were irradiated uniformly. With inhomogeneous dose distributions, on the other hand, different spatial distributions of "hot spots" may lead to different predictions of complication probability by cluster models. The result was that a higher complication probability resulted when hot spots were contiguous (clustered) than when they were dispersed, even if both situations are characterized by the same dose-volume histogram. A potential advantage of cluster models is to provide an easy, internally consistent way to predict complications arising from the inhomogeneous dose distributions that sometimes arise with intensity-modulated radiotherapy. CONCLUSION: Cluster models offer a new way to quantify complication probability in treatment situations in which a wide variety of hot-spot distributions occur.

Animals↗

PubMed2004

Quantification of volumetric and geometric changes occurring during fractionated radiotherapy for head-and-neck cancer using an integrated CT/linear accelerator system.

PURPOSE: Many patients receiving fractionated radiotherapy (RT) for head-and-neck cancer have marked anatomic changes during their course of treatment, including shrinking of the primary tumor or nodal masses, resolving postoperative changes/edema, and changes in overall body habitus/weight loss. We conducted a pilot study to quantify the magnitude of these anatomic changes with systematic CT imaging. METHODS AND MATERIALS: Fourteen assessable patients were enrolled in this pilot study. Eligible patients had to have a pathologic diagnosis of head-and-neck cancer, be treated with definitive external beam RT, and had have gross primary and/or cervical nodal disease measuring at least 4 cm in maximal diameter. All patients were treated using a new commercial integrated CT-linear accelerator system (EXaCT) that allows CT imaging at the daily RT sessions while the patient remains immobilized in the treatment position. CT scans were acquired three times weekly during the entire course of RT, and both gross tumor volumes (GTVs: primary tumor and involved lymph nodes) and normal tissues (parotid glands, spinal canal, mandible, and external contour) were manually contoured on every axial slice. Volumetric and positional changes relative to a central bony reference (the center of mass of the C2 vertebral body) were determined for each structure. RESULTS: Gross tumor volumes decreased throughout the course of fractionated RT, at a median rate of 0.2 cm(3) per treatment day (range, 0.01-1.95 cm(3)/d). In terms of the percentage of the initial volume, the GTVs decreased at a median rate of 1.8%/treatment day (range, 0.2-3.1%/d). On the last day of treatment, this corresponded to a median total relative loss of 69.5% of the initial GTV (range, 9.9-91.9%). In addition, the center of the mass of shrinking tumors changed position with time, indicating that GTV loss was frequently asymmetric. At treatment completion, the median center of the mass displacement (after corrections for daily setup variation) was 3.3 mm (range, 0-17.3 mm). Parotid glands also decreased in volume (median, 0.19 cm(3)/d range, 0.04-0.84 cm(3)/d), and generally shifted medially (median, 3.1 mm; range, 0-9.9 mm) with time. This medial displacement of the parotid glands correlated highly with the weight loss that occurred during treatment. CONCLUSION: Measurable anatomic changes occurred throughout fractionated external beam RT for head-and-neck cancers. These changes in the external contour, shape, and location of the target and critical structures appeared to be significant during the second half of treatment (after 3-4 weeks of treatment) and could have potential dosimetric impact when highly conformal treatment techniques are used. These data may, therefore, be useful in the development of an adaptive RT scheme (periodic adjustment of the conformal treatment plan) that takes into account such treatment-related anatomic changes. In theory, such a strategy would maximize the therapeutic ratio of RT.

Adult↗

PubMed2004

Molecular cloning and characterization of a new peptide deformylase from human pathogenic bacterium Helicobacter pylori.

Helicobacter pylori is a gram-negative pathogenic bacterium, which is associated with peptic ulcer disease and gastric cancer. It is urgent to discover novel drug targets for appropriate antimicrobial agents against this human pathogen. In bacteria, peptide deformylase (PDF) catalyzes the removal of a formyl group from the N-termini of nascent polypeptides. Due to its essentiality and absence in mammalian cells, PDF has been considered as an attractive target for the discovery of novel antibiotics. In this work, a new PDF gene (def) from H. pylori strain SS1 was cloned, expressed, and purified in Escherichia coli system. Sequence alignment shows that H. pylori PDF (HpPDF) shares about 40% identity to E. coli PDF (EcPDF). The enzymatic properties of HpPDF demonstrate its relatively high activity toward formyl-Met-Ala-Ser, with K(cat) of 3.4s(-1), K(m) of 1.7 mM, and K(cat) / K(m) of 2000M(-1)s(-1). HpPDF enzyme appears to be fully active at pH between 8.0 and 9.0, and temperature 50 degrees C. The enzyme activity of Co(2+)-containing HpPDF is apparently higher than that of Zn(2+)-containing HpPDF. This present work thereby supplies a potential platform that facilitates the discovery of novel HpPDF inhibitors and further of possible antimicrobial agents against H. pylori.

Amidohydrolases↗

PubMed2004

Evaluation of a contour-alignment technique for CT-guided prostate radiotherapy: an intra- and interobserver study.

PURPOSE: The recent introduction of integrated CT/linear accelerator systems may mean that daily CT localization can become a reality in the clinic, possibly allowing further dose escalation to the prostate while limiting unwanted doses to the rectum and bladder. However, the implementation of CT localization is currently impeded by the lack of precise and robust techniques to align the treatment plan with the daily CT images. The purpose of this study was to evaluate a manual alignment technique, in which the gross target volume contours are overlaid on the daily CT images and then shifted to match the structures visible in the images. METHODS AND MATERIALS: A total of 28 CT image sets were taken before the standard delivery of intensity-modulated radiotherapy for prostate cancer for 2 patients. Seven observers (four radiation oncologists and three medical physicists) manually shifted the gross target volume contours from the treatment plan to best match the daily CT images. One observer repeated the process 1 week later to evaluate intraobserver variations. The experiment was then repeated, but the CT images from the original treatment plan were used as a reference to reduce interobserver uncertainty when aligning the contours. The shifts in prostate position found by different observers, both with and without reference data, were evaluated using a factorial analysis of variance to determine the standard errors of measurement for the intra- and interobserver uncertainty (SEM(intra) and SEM(inter), respectively). The differences in the SEM for the two groups of observers (radiation oncologists and medical physicists), the two alignment techniques (with and without reference information), and the two patients were evaluated using the t test at 90% confidence levels. RESULTS: With no reference information, the SEM(inter) using one patient data set (Patient 1) was 0.8 mm, 2.0 mm, and 2.2 mm in the right-left (RL), anterior-posterior (AP), and superior-inferior (SI) directions, respectively. The use of the treatment plan as a reference reduced the SEM(inter) to 0.7 mm, 1.0 mm, and 1.6 mm in the RL, AP, and SI directions, respectively. In Patient 2, localization of the prostate was more difficult; the best SEM(inter) achieved with this patient was 0.8 mm, 1.9 mm, and 2.0 mm in the RL, AP, and SI directions, respectively. The SEM(intra) values with Patient 1 were also slightly better than with Patient 2. When reference data were used, the SEM(intra) value was 0.5 mm, 0.7 mm, and 0.5 mm for Patient 1 and 0.6 mm, 1.0 mm, and 0.7 mm for Patient 2 in the RL, AP, and SI directions, respectively. Despite the larger than expected interobserver variation reported here, the SEM(inter) was smaller than the typical day-to-day variation in prostate position. The contour alignment technique may still be useful to aid daily prostate localization or in a correction scheme to minimize the effect of target positional error. CONCLUSION: The interobserver uncertainties associated with aligning the gross target volume contours with daily CT images were sufficiently small that this method may be used for daily CT localization of the prostate. The use of a reference image is important to improve the consistency among different users in this technique.

Analysis of Variance↗

PubMed2004

Dose-volume response analyses of late rectal bleeding after radiotherapy for prostate cancer.

PURPOSE: To compare the fits of various normal tissue complication probability (NTCP) models to a common set of late rectal toxicity data, with the aim of identifying the best model for predicting late rectal injury after irradiation. METHODS AND MATERIALS: Late toxicity data from 128 prostate cancer patients treated on protocol with three-dimensional conformal radiotherapy at The University of Texas M.D. Anderson Cancer Center (UTMDACC) were analyzed. The dose-volume histogram for total rectal volume, including contents, was obtained for each patient, and the presence or absence of Grade 2 or worse rectal bleeding within 2 years of treatment was scored. Five different NTCP models were fitted to the data using maximum likelihood analysis: the Lyman model, the mean dose model, a parallel architecture model, and models based on either a cutoff dose or a cutoff volume. RESULTS: All five of the NTCP models considered provided very similar fits to the UTMDACC rectal bleeding data. In particular, none of the more highly parameterized models (the four-parameter parallel model, three-parameter Lyman model, or three-parameter cutoff dose and volume models) provided a better fit than the simplest of the models, the two-parameter NTCP model describing rectal bleeding as a probit function of mean dose to rectum. CONCLUSION: No dose-volume response model has yet been identified that provides a better description of the UTMDACC rectal toxicity data than the mean dose model. Because this model has relatively low predictive accuracy, the need to identify a better model remains.

Dose-Response Relationship, Radiation↗

PubMed2004

Epidemiology of gastroesophageal reflux disease: a general population-based study in Xi'an of Northwest China.

AIM: Gastroesophageal reflux disease (GERD) is a common disorder in the Western population, but detailed population-based data in China are limited. The aim of this study was to understand the epidemiology of symptomatic gastroesophageal reflux (SGER) in adults of Xi'an, a northwestern city of China, and to explore the potential risk factors of GERD. METHODS: Symptoms suggestive of GERD, functional dyspepsia (FD), irritable bowel syndrome (IBS), upper respiratory diseases and some potential risk factors were investigated in a face-to-face manner in a region-stratified random samples of 2789 residents aged 18-70 years in Xi'an by using a standardized questionnaire. METHODS: With a response rate of 91.8%, the prevalence of SGER was 16.98% (95% CI, 14.2-18.92) in Xi'an adults, and no gender-related difference was observed (P<0.05). SGER was more common among subjects aged 30-70 years than in those aged 18-29 years (P<0.01). The prevalence of SGER in rural, urban and suburban subjects was 21.07%, 17.44% and 12.12%, respectively, and there was a significant difference between rural, urban and suburban regions (P<0.05). Compared with subjects without SGER, the prevalence of symptoms suggestive of FD and IBS, pneumonia, asthma, bronchitis, laryngitis, pharyngitis, chronic cough, wheeze, globus sensation, oral ulcer and snore was significantly increased in subjects with SGER (P<0.01). Heavy smoking (OR=5.76; CI, 3.70-6.67), heavy alcohol use (OR=2.85; CI, 1.67-4.49), peptic ulcer (OR=5.76; CI, 3.99-8.32), cerebral palsy (OR=3.97; CI, 1.97-8.00), abdominal operation (OR=2.69; CI, 1.75-4.13), obesity (OR=2.16; CI, 1.47-3.16), excessive food intake (OR=1.43; CI, 1.17-1.15), sweet food (OR=1.23; CI, 0.89-1.54), and consumption of coffee (OR=1.23; CI, 0.17-2.00) were independently associated with SGER. The episodes of GERD were commonly precipitated by dietary factors (66.05%), followed by body posture (26.54%), ill temper (23.72%), fatigue (22.32%) and stress (10.93%). CONCLUSION: GERD is common in Xi'an's adult population with a mild or moderate degree. The etiology and pathogenesis of GERD are probably associated with FD, IBS, and some respiratory, laryngopharyngeal and odontostological diseases or symptoms. Some lifestyles, diseases and dietary factors are the risk factors of GERD.

Adolescent↗

PubMed2004

Characterization of rectal normal tissue complication probability after high-dose external beam radiotherapy for prostate cancer.

PURPOSE: Conformal radiotherapy (RT) has allowed radiation dose escalation to improve the outcome of prostate cancer. With higher doses, concern exists that rectal injury may increase. This study analyzed the utility and limitations of the widely used Lyman-Kutcher- Burman (LKB) normal tissue complication probability model in projecting the hazards of rectal complication with high-dose RT. METHODS AND MATERIALS: A total of 128 patients were included in this study. These patients were treated with three-dimensional conformal RT alone at the University of Texas M.D. Anderson Cancer Center between 1992 and 1999. Patients were treated to 46 Gy with a four-field box technique followed by a six-field arrangement to boost the total dose to 78 Gy. All doses were delivered at 2 Gy/fraction to the isocenter. The minimal follow-up was 2 years. The end point for analysis was Grade 2 or worse rectal bleeding by 2 years. The LKB model was fitted to the data using the maximal likelihood method. RESULTS: Of the 128 patients, 29 experienced Grade 2 or worse rectal bleeding by 2 years. For the entire cohort, the parameters obtained from the fit of the LKB model were as follows: the volume factor was n = 3.91 (95% confidence interval [CI] 0.031 to infinity ), dose associated with 50% chance of complication for uniform whole rectal irradiation [TD50(1)] was 53.6 Gy (95% CI 50.0-75.1), and a determinant of the steepness of the dose-response curve, (m), was 0.156 (95% CI 0.036-0.271). A statistically significant difference was found in the rate of postradiation rectal bleeding in patients with hemorrhoids vs. those without hemorrhoids. The parameters obtained for the patients without hemorrhoids were as follows: n = 0.746 (95% CI 0.026 to infinity ), TD50(1) 56.7 Gy (95% CI 49.9-75.2), and m 0.092 (95% CI 0.019-0.189). CONCLUSION: Our analysis suggests a dose response for rectal bleeding probability along with a volume effect. We found that the LKB model might have limited utility in determining a large volume effect. We further suggest that LKB model should be used with caution in clinical practice.

Dose-Response Relationship, Radiation↗

PubMed2004

Feasibility of sparing lung and other thoracic structures with intensity-modulated radiotherapy for non-small-cell lung cancer.

PURPOSE: To investigate the possibility of using intensity-modulated radiotherapy (IMRT) to reduce the irradiated volumes of the normal lung and other critical structures in the treatment of non-small-cell lung cancer (NSCLC) and to investigate the effect of IMRT on the potential of spreading low doses to large volumes of normal tissues in such treatment. METHODS AND MATERIALS: A retrospective treatment planning study was performed to compare IMRT and conventional three-dimensional conformal radiation therapy (3D-CRT) for 10 NSCLC patients (Stage I-IIIB). In the IMRT plans, three to nine coplanar beams were designed to treat 95% of the planning target volume with 63 Gy and to minimize the volumes of the normal lung, esophagus, heart, and spinal cord irradiated above their tolerance doses. The two types of plans were compared with respect to the planning target volume coverage, dose-volume histograms, and other dosimetric indexes of the normal structures. RESULTS: Comparing the nine-beam IMRT plan with the 3D-CRT plan, the percentage of lung volume that received >20 Gy and the mean lung dose were reduced for all cases, with a median reduction of 8% and 2 Gy, respectively. An additional reduction of the >5-Gy volume and >10-Gy volume for the lung and thoracic tissue was more difficult with IMRT, although still possible using fewer beams in IMRT. The integral dose to the entire thorax was equivalent and even reduced for 8 of 10 cases using IMRT. CONCLUSION: It is possible to reduce the volumes of low doses (such as the >10-Gy volume and >20-Gy volume) for thoracic normal tissues using IMRT. The increased integral dose and low-dose volumes can be avoided for IMRT if such concerns are addressed carefully in the inverse planning process and with optimization of the IMRT beam configuration.

Carcinoma, Non-Small-Cell Lung↗

PubMed2004

The delivery of IMRT with a single physical modulator for multiple fields: a feasibility study for paranasal sinus cancer.

PURPOSE: This study describes a new intensity-modulated radiation therapy (IMRT) delivery method that utilizes a single modulator to deliver multiple fields ("multifield modulator"). This technique reduces the treatment time and manufacturing costs typically associated with modulator-IMRT. Technical feasibility was evaluated for treating paranasal sinus cancers. METHODS AND MATERIALS: Technical feasibility was measured by three criteria: The dose distributions of the multifield modulator-IMRT plans should offer improvements over those produced by 3D conformal plans and be equivalent to those of step-and-shoot multileaf collimator (MLC) IMRT plans, the manufactured modulators should meet quality assurance specifications, and the effort required to use this technology should not substantially exceed the effort required for current IMRT practice. Seven paranasal cancer cases were examined. The Wilcoxon signed rank test was used for statistical analysis. RESULTS: Multifield modulator-IMRT plans can improve target coverage while reducing critical structure doses compared to 3D conformal plans. Multifield modulator-IMRT plans are at least equivalent to the corresponding step-and-shoot MLC-IMRT plans. Multifield modulators can be constructed to meet design specifications in quality assurance tests. The time required for manufacturing, quality assurance, and treatment delivery using multifield modulators was measured and found to be only slightly greater than that for current IMRT treatment methods. CONCLUSIONS: IMRT treatments using multifield modulators for paranasal sinus tumors are feasible. Clinics may find it worthwhile to commit the minimal extra time for quality assurance and treatment to benefit from the improved dose distribution and lack of interplay between MLC leaf motion and internal target motion.

Feasibility Studies↗

PubMed2004

Effects of estradiol on liver estrogen receptor-alpha and its mRNA expression in hepatic fibrosis in rats.

AIM: Estradiol treatment regulates estrogen receptor (ER) level in normal rat liver. However, little information is available concerning the role of estrogen in regulating liver ER in hepatic fibrosis in rats. The present study was conducted to determine whether estradiol treatment in CCl4-induced liver fibrosis of female and ovariectomized rats altered liver ERalpha and its mRNA expression, and to investigate the possible mechanisms. METHODS: Seventy female rats were divided into seven groups with ten rats in each. The ovariectomy groups were initiated with ovariectomies and the sham operation groups were initiated with just sham operations. The CCl4 toxic fibrosis groups received 400 mL/L CCl4 subcutaneously at a dose of 2 mL/kg twice weekly. Estrogen groups were treated subcutaneously with estradiol 1 mg/kg, the normal control group and an ovariectomy group received injection of peanut oil vehicle twice weekly. At the end of 8 weeks, all the rats were killed to detect their serum and hepatic indicators, their hepatic collagen content, and liver ER and ER mRNA expression. RESULTS: Estradiol treatment in both ovariectomy and sham ovariectomy groups reduced liver levels of ALT (from 658 +/- 220 nkat/L to 311 +/- 146 nkat/L and 540 +/- 252 nkat/L to 314 +/- 163 nkat/L, P<0.05) and AST (from 697 +/- 240 nkat/L to 321 +/- 121 nkat/L and 631 +/- 268 nkat/L to 302 +/- 153 nkat/L, P<0.05), increased serum nitric oxide (NO) level (from 53.7 +/- 17.1 micromol/L to 93.3 +/- 24.2 micromol/L and 55.3 +/- 23.1 micromol/L to 87.5 +/- 23.6 micromol/L, P<0.05) and hepatic nitric oxide synthase (NOS) activity (from 1.73 +/- 0.71 KU/g to 2.49 +/- 1.20 KU/g and 1.65 +/- 0.46 KU/g to 2.68 +/- 1.17 KU/g, P<0.05), diminished the accumulation of hepatic collagen, decreased centrolobular necrotic areas as well as the inflammatory reaction in rats subjected to CCl4. The positive signal of ER and ER mRNA distributed in parenchymal and non-parenchymal hepatic cells, especially near the hepatic centrolobular and periportal areas. Ovariectomy decreased ER level (from 10.2 +/- 3.2 to 4.3 +/- 1.3) and ER mRNA expression (from 12.8 +/- 2.1 to 10.9 +/- 1.3) significantly (P<0.05). Hepatic ER and ER mRNA concentrations were elevated after treatment with estradiol in both ovariectomy (15.8 +/- 2.4, 20.8 +/- 3.1) and sham ovariectomy (18.7 +/- 3.8, 23.1 +/- 3.7) fibrotic groups (P<0.05). CONCLUSION: The increase in hepatic ER and mRNA expression may be part of the molecular mechanisms underlying the suppressive effect of estradiol on liver fibrosis induced by CCl4 administration.

Alanine Transaminase↗

PubMed2004

Novel antibacterial diterpenoids from Larix chinensis Beissn.

Two novel labdane-type diterpenoids, butanedioic acid mono[(13S)-13-hydroxylabda-8(17),14-dien-19-yl] ester (1) and butanedioic acid bis[(13S)-13-hydroxylabda-8(17),14-dien-19-yl] ester (2), along with the eleven known diterpenoids 3-13 and three other known compounds, were isolated from the bark of Larix chinensis. Their structures were elucidated both spectroscopically and chemically. The major diterpenoids 1-9, 11, and 13, as well as the very abundant phenolic compound 16, were subjected to antibacterial and cytotoxic bioassays. Compounds 7 and 9 showed remarkable in vitro inhibition of Staphylococcus aureus and S. epidermidis (MIC = 37-73 microM).

Anti-Bacterial Agents↗

PubMed2004

High-dose intensity modulated radiation therapy for prostate cancer.

The trend in prostate cancer radiation over the past several years has been to increase the dose to the gland while minimizing the dose to normal tissues. Intensity modulated radiation therapy is a computer-driven treatment planning and delivery system that has shown promise in improving disease-free outcome while decreasing the associated gastrointestinal and urinary complication rates. This technique continues to evolve, working toward image-guided radiation therapy, which is adjusted daily for positional and architectural changes of the gland.

Humans↗

PubMed2004

Speed and convergence properties of gradient algorithms for optimization of IMRT.

Gradient algorithms are the most commonly employed search methods in the routine optimization of IMRT plans. It is well known that local minima can exist for dose-volume-based and biology-based objective functions. The purpose of this paper is to compare the relative speed of different gradient algorithms, to investigate the strategies for accelerating the optimization process, to assess the validity of these strategies, and to study the convergence properties of these algorithms for dose-volume and biological objective functions. With these aims in mind, we implemented Newton's, conjugate gradient (CG), and the steepest decent (SD) algorithms for dose-volume- and EUD-based objective functions. Our implementation of Newton's algorithm approximates the second derivative matrix (Hessian) by its diagonal. The standard SD algorithm and the CG algorithm with "line minimization" were also implemented. In addition, we investigated the use of a variation of the CG algorithm, called the "scaled conjugate gradient" (SCG) algorithm. To accelerate the optimization process, we investigated the validity of the use of a "hybrid optimization" strategy, in which approximations to calculated dose distributions are used during most of the iterations. Published studies have indicated that getting trapped in local minima is not a significant problem. To investigate this issue further, we first obtained, by trial and error, and starting with uniform intensity distributions, the parameters of the dose-volume- or EUD-based objective functions which produced IMRT plans that satisfied the clinical requirements. Using the resulting optimized intensity distributions as the initial guess, we investigated the possibility of getting trapped in a local minimum. For most of the results presented, we used a lung cancer case. To illustrate the generality of our methods, the results for a prostate case are also presented. For both dose-volume and EUD based objective functions, Newton's method far outperforms other algorithms in terms of speed. The SCG algorithm, which avoids expensive "line minimization," can speed up the standard CG algorithm by at least a factor of 2. For the same initial conditions, all algorithms converge essentially to the same plan. However, we demonstrate that for any of the algorithms studied, starting with previously optimized intensity distributions as the initial guess but for different objective function parameters, the solution frequently gets trapped in local minima. We found that the initial intensity distribution obtained from IMRT optimization utilizing objective function parameters, which favor a specific anatomic structure, would lead to a local minimum corresponding to that structure. Our results indicate that from among the gradient algorithms tested, Newton's method appears to be the fastest by far. Different gradient algorithms have the same convergence properties for dose-volume- and EUD-based objective functions. The hybrid dose calculation strategy is valid and can significantly accelerate the optimization process. The degree of acceleration achieved depends on the type of optimization problem being addressed (e.g., IMRT optimization, intensity modulated beam configuration optimization, or objective function parameter optimization). Under special conditions, gradient algorithms will get trapped in local minima, and reoptimization, starting with the results of previous optimization, will lead to solutions that are generally not significantly different from the local minimum.

Algorithms↗

PubMed2004

Effects of different infusion volumes on hemodynamics of portal hypertension canines after hemorrhagic shock.

BACKGROUND: Portal hypertension (PHT) with upper gastrointestinal hemorrhage as its chief complication is a very common disease with great harm to humans. The effects of infusion volume, speed, and type on hemodynamics in case of cirrhosis, PHT esophageal variceal bleeding, and their mechanism should be clarified. This study was designed to assess the effects of different infusion volumes on hemodynamics of PHT canines after hemorrhagic shock (HS). METHODS: PHT canine models were made by chronic embolization via coarctating half of the main portal vein with silk suture. Two weeks later, the models were subjected to hemorrhagic shock by quick femoral artery venesection. The canines were divided into two groups to resuscitate: one to receive a large volume of infusion (n=6) (large volume infusion group) and the other to receive a small volume of infusion (n=6) (small volume infusion group). Hemodynamic indexes of PHT canines after HS and infusion were observed closely. RESULTS: The PHT canines showed a series of hemodynamical changes in hemorrhagic shock stage, which aggravated hemodynamical disorder in PHT. After quick infusion, mean arterial pressure (MAP), inferior vena cava pressure (IVCP), portal venous pressure (PVP), portal vein pressure gradient (PVPG), portal vein blood flow (PVBF), hepatic artery blood flow (HABF) and hepatic blood flow (HBF) increased significantly. These indexes in the large volume infusion group were higher than those in the small volume infusion group. Portal vascular resistance (PVR), splanchnic vascular resistance (SVR), hepatic arterial resistance (HAR) decreased significantly, but PVP, PVPG, PVBF, HABF and HBF showed a rebounding increase above the baseline values in the large volume infusion group. The changes of PVP, PVPG, PVBF, HABF and HBF were in parallel with those of MAP and inferior vena cava pressure (IVCP), without a rebounding increase in the small volume infusion group. In the large volume infusion group PVPG increased earlier and more significantly than did PVP; moreover PVPG exceeded the baseline by 13%, making the possibility of rebleeding great. In the small volume infusion group, PVPG was lower than the baseline by more than 22%, indicating a small possibility of rebleeding. SVR and HAR were lower in the large volume infusion group. PVP, PVPG, PVBF, HABF and HBF were positively correlated with accumulated volume of vein infusion. PVR showed a positive correlation with accumulated volume of vein infusion in the small volume infusion group. HAR was negatively correlated with accumulated volume of vein infusion in the large volume infusion group. CONCLUSIONS: PHT canines after HS, resuscitated by vein infusion, may show a rebounding increase of PVP, PVPG, PVBF, HABF and HBF above the baseline values in the large volume infusion group but not in the small volume infusion group. A large volume infusion causes PVP, PVPG, PVBF, HABF and HBF to increase higher than does a small volume infusion.

Animals↗

PubMed2003

Hazards of dose escalation in prostate cancer radiotherapy.

PURPOSE: To assess the benefit of escalating the dose in definitive prostate cancer radiotherapy vs. the associated risk of complications. MATERIALS AND METHODS: Between 1987 and 1999, 1087 patients with clinical Stage T1b-T3 adenocarcinoma of the prostate were definitively irradiated without hormonal therapy and had a pretreatment serum prostate-specific antigen (PSA) and Gleason score recorded. The median follow-up was 65 months. Doses ranged from 64 to 78 Gy, with the treatment techniques corresponding to the year of therapy and the prescribed dose. A total of 301 patients were treated on a randomized protocol to either 70 or 78 Gy. Also, 163 patients were treated with three-dimensional conformal therapy and had dose-volume histograms available for review. RESULTS: Tumor stage, grade, pretreatment PSA level, and radiation dose were all independent predictors of PSA disease-free survival (PSA-DFS) in multivariate analysis. The hazard rate for biochemical failure peaked at 1.5-3 years after radiotherapy. Although a statistically significant dose effect on PSA-DFS was found in the pretreatment PSA levels of those with both < or =10 ng/mL and >10 ng/mL, in those with a pretreatment PSA < or =10 ng/mL, the improvement in outcome was only seen going from a dose level of 64-66 Gy to 68-70 Gy with a 5-year PSA-DFS rate of 66% vs. 81% (p <0.0001). This was also confirmed by the data from the randomized patients who showed no difference in outcome whether treated to 70 Gy or 78 Gy. In patients with a pretreatment PSA level >10 ng/mL, a statistically significant improvement was found in disease-free outcome among the 64-66-Gy, 68-70-Gy, and 78-Gy levels. PSA-DFS was approximately 50% better at each higher dose level at 5 and 8 years after treatment. The dose had a statistically significant impact in both intermediate- and high-risk groups. Rectal morbidity was both dose and volume related. Although at 5 years after therapy, the Grade 2-3 rectal complication rate was twice as high for patients treated to 78 Gy than to 70 Gy, 26% vs. 12%, this risk could be markedly diminished by adhering to dose-volume constraints. CONCLUSIONS: In intermediate- and high-risk prostate cancer patients, although it appears that radiation-dose escalation may improve PSA-DF outcome, the price paid in treatment morbidity can be high without adequate attention to dose-volume constraints of normal tissue. Care must be taken to consider not only the hazard of tumor recurrence but also that of complications.

Adenocarcinoma↗