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Biomedical subjects

W Zhen

Publications and source records attributed to W Zhen.

At least 19 recordsLinked to original sources

National survey of head and neck verrucous carcinoma: patterns of presentation, care, and outcome.

BACKGROUND: Verrucous carcinoma is distinguished by controversy regarding appropriate diagnosis and treatment. This study provides a contemporary survey of demographics, patterns of care, and outcome for this disease in the United States. METHODS: The National Cancer Data Base had 2350 cases of verrucous carcinoma of the head and neck diagnosed between 1985 and 1996. Statistical procedures included chi-square analyses, Student t tests, and relative survival. RESULTS: Tumors originated most frequently in the oral cavity (55.9%) and larynx (35.2%). Although most patients were male (60.0%), oral cavity tumors were more common among older females. The most prevalent treatment was surgery alone (69.7%), followed by surgery combined with irradiation (11.0%) and irradiation alone (10.3%). For oral cavity tumors, surgery alone was more common among early (85.8%) than advanced cases (56.9%); a larger proportion of advanced disease received radiation alone or surgery and irradiation combined. Most laryngeal tumors were treated with surgery (60.3% for early and 55.6% for advanced disease), but a higher proportion received radiation alone or surgery combined with radiation compared with oral cavity cases. Five-year relative survival was 77.9%. For localized disease, survival after surgery was 88.9% compared with 57.6% after irradiation. CONCLUSIONS: Demographic differences implicate different mechanisms of carcinogenesis for verrucous carcinoma arising in the oral cavity and the larynx. Although selection bias may account for the differences observed, patients receiving initial treatment with surgery had better survival than those treated with irradiation, especially for cases originating in the oral cavity.

Adult↗

Analysis of mono- and oligosaccharides by multiwavelength surface plasmon resonance (SPR) spectroscopy.

Surface plasmon resonance (SPR) spectra of different saccharides were collected using a home-made multiwavelength SPR apparatus. Pentoses, hexoses, disaccharides and a trisaccharide were distinguished from one another according to their SPR spectra collected at the same concentration. The spectra were also used for the quantitation of sugars by exploring the linear relationship between resonance wavelength and solute concentration. The dynamic linear ranges for the determination of glucose, sucrose and raffinose are 0.01-0.2, 0.005-0.1 and 0.0025-0.1 mol/L, respectively. The SPR spectrum of a mixture of two components was investigated. While the experiments have not been carried out, the implications from this work are that the technique would be applicable to mixtures containing more than two components.

Monosaccharides↗

Commissioning of Peacock System for intensity-modulated radiation therapy.

The Peacock System was introduced to perform tomographic intensity-modulated radiation therapy (IMRT). Commissioning of the Peacock System included the alignment of the multileaf intensity-modulating collimator (MIMiC) to the beam axis, the alignment of the RTA device for immobilization, and checking the integrity of the CRANE for indexing the treatment couch. In addition, the secondary jaw settings, couch step size, and transmission through the leaves were determined. The dosimetric data required for the CORVUS planning system were divided into linear accelerator-specific and MIMiC-specific. The linear accelerator-specific dosimetric data were relative output in air, relative output in phantom, percent depth dose for a range of field sizes, and diagonal dose profiles for a large field size. The MIMiC-specific dosimetric data were the in-plane and cross-plane dose profiles of a small and a large field size to derive the penumbra fit. For each treatment unit, the Beam Utility software requires the data be entered into the CORVUS planning system in modular forms. These modules were treatment unit information, angle definition, configuration, gantry and couch angles range, dosimetry, results, and verification plans. After the appropriate machine data were entered, CORVUS created a dose model. The dose model was used to create known simple dose distribution for evaluation using the verification tools of the CORVUS. The planned doses for phantoms were confirmed using an ion chamber for point dose measurement and film for relative dose measurement. The planning system calibration factor was initially set at 1.0 and will be changed after data on clinical cases are acquired. The treatment unit was released for clinical use after the approval icon was checked in the verification plans module.

Humans↗

Quality assurance procedures for the Peacock system.

The Peacock system is the product of technological innovations that are changing the practice of radiotherapy. It uses dynamic beam modulation technique and inverse planning algorithm, both of which are new methodologies, to perform intensity-modulation radiation therapy (IMRT). The quality assurance (QA) procedure established by Task Group No. 40 did not adequately consider these emerging modalities. A review of literature indicates that published articles on QA procedures concentrate primarily on the verification of dose delivered to phantom during commissioning of the system and dose delivered to phantom before treating patients. Absolute dose measurements using ion chambers and relative dose measurements using film dosimetry have been used to verify delivered doses. QA on equipment performance and equipment safety is limited. This paper will discuss QA on equipment performance, equipment safety, and patient setup reproducibility.

Algorithms↗

Viewpoints to consider in the development of MLC and IMRT programs.

Operational and administrative considerations for the development and implementation of either multileaf collimation (MLC) or non-MLC-based intensity-modulated radiation therapy (IMRT) will be discussed with respect to the impact that this will have on a radiation oncology department. The methodologies that are used in the development process will be reviewed in both the operational and administrative components. Operational issues addressing the potential clinical impact the department will experience, along with the beneficial outcome for the patients, will be major points in this review process. Administrative considerations generally focus on the financial impact that the department and hospital will have to deal with in determining cost benefits of this capital expenditure. This overview will focus on some key discussion points with the incorporation of MLC and IMRT into a radiation oncology department treatment program.

Financial Management↗

Leaf sequencing techniques for MLC-based IMRT.

The nonuniform fields required by intensity-modulation radiation therapy (IMRT) can be delivered using conventional multileaf collimators (MLC) as beam modulators. In MLC-based IMRT, the nonuniform field is initially converted into an intensity map represented as a matrix of beam intensities. The intensity map is then decomposed into a series of subfields or segments of uniform intensities. Although there are many ways of segmenting the beam intensity matrix, a resulting subfield is only deliverable if it satisfies the constraints imposed by the MLC. These constraints exist as a result of the design of the MLC. The simplest constraint of the MLC is that its pairs of leaves can only move in and out in one dimension. Additional constraints include collision of opposing leaves and the need to match the tongue-and-groove to reduce interleaf leakage. The practical aspect of MLC-based IMRT requires that an optimized algorithm decomposes the nonuniform field into the least number of segments and therefore reduces the delivery time. This paper examines the static use and the dynamic use of MLCs to perform MLC-based IMRT.

Radiotherapy, Conformal↗

Commissioning and quality assurance for MLC-based IMRT.

The commissioning and quality assurance (QA) associated with the implementation of linear accelerator multileaf collimator (MLC)-based intensity-modulated radiation therapy (IMRT) at the University of Nebraska Medical Center are described. Our MLC-based IMRT is implemented using the PRIMUS linear accelerator interface through the IMPAC record and verification system to the CORVUS treatment planning system. The "step-and-shoot" technique is used for this MLC-based IMRT. Commissioning process requires the verification of predefined parameters available on the CORVUS and the collection of some machine data. The machine data required are output factor in air and output factor in phantom, and percent depth dose for a number of field sizes. In addition, inplane and crossplane dose profiles of 4 x 4 cm and 20 x 20 cm field sizes and diagonal dose profiles of a large field size have to be measured. Validation of connectivity and dose model includes the use of uniform intensity bar strips, triangular-shaped nonuniform intensity bar strip, and N-shaped target. QA procedure follows the recommendation of the AAPM Task Group No. 40 report. In addition, the leaf position accuracy and reproducibility of the MLC should be checked at regular intervals. The dose validation is implemented through the hybrid plan where the patient beam parameters are applied to a flat phantom. Independent dose calculation method is used to confirm the dose delivery plan and data input to the CORVUS.

Equipment Design↗

Esthesioneuroblastoma: the University of Iowa experience 1978-1998.

OBJECTIVE: Esthesioneuroblastoma is rare and the best treatment has yet to be defined. The purpose of this study is to analyze the natural history, treatment, and patterns of failure of esthesioneuroblastoma treated at one institution. METHODS: Between 1978 and 1998, 13 patients with esthesioneuroblastoma were identified using the University of Iowa Tumor Registry. All patients were staged according to Kadish criteria. Mean follow-up was 6.3 years. Six patients had 5 or more years of follow-up and four had follow-up exceeding 9.5 years. One patient was lost to follow-up at 36 months. RESULTS: No patients had Kadish stage A disease, five were stage B, and eight stage C. Overall actuarial 5- and 10-year survival rate was 61% and 24%, respectively. Disease-free survival rate at 5 and 10 years was 56% and 42%, respectively. Seven patients have died, three of intercurrent disease and three of disease progression, one with an unknown disease status. Six patients remain alive, three without evidence of disease and three have experienced a local or regional recurrence. Five patients who were initially controlled developed recurrence, three local only, one locoregional, and one regional and distant. Median time to failure was 96 months. All patients with follow-up exceeding 12 years have experienced either a local or regional recurrence. Survival after salvage therapy in these patients ranged from 3 to 12 years. CONCLUSION: Esthesioneuroblastoma has a long natural history characterized by frequent local or regional recurrence after conventional treatment. Successful retreatment can lead to prolonged survival.

Adult↗

Long-term effects in children treated with radiotherapy for head and neck rhabdomyosarcoma.

PURPOSE: To examine the long-term effects of treatment in children receiving radiotherapy for head and neck rhabdomyosarcoma. METHODS: From 1967 to 1994, a total of 30 children with head and neck rhabdomyosarcoma received megavoltage radiotherapy at one institution. Seventeen patients (57%) have survived and have at least a 5-year follow-up. There were 11 males and 6 females, with a median age of 5.7 years (range 2.2-11.6) at the time of radiotherapy. Tumor location was orbit in 6 patients, infratemporal fossa in 4, paranasal sinuses in 2, and supraglottic larynx in 2; the nasopharynx, pterygopalatine fossa, and parotid gland were sites for the remaining children. All but 2 patients had tumors of embryonal histology. The Intergroup Rhabdomyosarcoma Study (IRS) Group was I in 2, II in 3, and III in 11 children; 1 patient had a recurrent tumor after surgery alone. Radiotherapy volume was the primary tumor or tumor bed in 13, tumor and whole brain in 3, and tumor and craniospinal axis in 1. Median radiotherapy dose to the primary site was 5,040 cGy (range 4,140-6,500) and to the whole brain was 3,000 cGy. All but 1 were treated with 150-200-cGy fractions; 1 patient received 250-cGy fractions for a tumor in the larynx. Chemotherapy was vincristine (V), actinomycin-D (A), and cyclophosphamide (C) in 10 patients, VAC + adriamycin in 2, VA in 1, VA + ifosfamide in 1, VC + adriamycin in 1, and none in 2. One patient had salvage chemotherapy consisting of cisplatin and etoposide. Median follow-up time was 20 years (range 7.5-33). RESULTS: Late effects of treatment were seen in all patients and included facial growth retardation in 11, neuroendocrine dysfunction in 9, visual/orbital problems in 9, dental abnormalities in 7, hearing loss in 6, and hypothyroidism in 3. Intellectual and academic delays were documented in 3 patients who had received whole brain radiotherapy. While neuroendocrine, thyroid, dental, and cognitive sequelae were primarily attributed to radiotherapy, hearing loss was thought to be a direct result of tumor destruction and, in 1 case, cisplatin chemotherapy. Late effects at or beyond 10 years from radiotherapy were few, but severe, and included chondronecrosis, esophageal stenosis, second malignancy, and brain hemorrhage. CONCLUSION: Late effects of treatment in children receiving radiotherapy for head and neck rhabdomyosarcoma are frequent. Although radiotherapy is a significant contributor of neuroendocrine, dental, thyroid, and cognitive toxicity, it is not usually implicated with hearing loss. Late toxicity of treatment beyond 10 years is not as frequent as those occurring within 10 years of therapy.

Antineoplastic Combined Chemotherapy Protocols↗

National cancer database report on chondrosarcoma of the head and neck.

BACKGROUND: Management of chondrosarcoma of the head and neck is largely based on single-institution reports with small numbers accrued over several decades. METHODS: The American College of Surgeons' National Cancer Data Base included 400 cases of chondrosarcoma of the head and neck diagnosed between 1985 and 1995. Chi square analyses of selected contingency tables and Wilcoxon regression analyses of selected survival stratifications were performed. RESULTS: Histologic types included conventional (80.8%), myxoid (10.5%), and mesenchymal (8.8%). The mesenchymal and myxoid subtypes were rare among white patients (17.1%) and more common among African-American (31.8%) and Hispanic patients (44.9%). Treatment was most commonly surgery alone (59.5%) and surgery with irradiation (21.0%). Disease-specific survival was 87.2% at 5 years and 70.6% at 10 years. Worse 5-year survival was associated with higher grade (67.3%), regional or distant spread (71.0%), and the myxoid (45.0%) or mesenchymal (53.2%) subtypes. CONCLUSIONS: Chondrosarcoma of the head and neck encompasses a variety of lesions that differ substantially by demographic and tumor characteristics. Individual tumors can be classified further according to site of origin, histologic subtype, and tumor grade, which can be used to predict biologic behavior and prognosis.

Adult↗

Pixel analysis of MR perfusion imaging in predicting radiation therapy outcome in cervical cancer.

The purpose of this study was to assess heterogeneity of tumor microcirculation determined by dynamic contrast-enhanced magnetic resonance (MR) imaging and its prognostic value for tumor radiosensitivity and long-term tumor control using pixel-by-pixel analysis of the dynamic contrast enhancement. Sixteen patients with advanced cervical cancer were examined with dynamic contrast-enhanced MR imaging at the time of radiation therapy. Pixel-by-pixel statistical analysis of the ratio of post- to precontrast relative signal intensity (RSI) values in the tumor region was performed to generate pixel RSI distributions of dynamic enhancement patterns. Histogram parameters were correlated with subsequent tumor control based on long-term cancer follow-up (median follow-up 4.6 years; range 3.8-5.2 years). The RSI distribution histograms showed a wide spectrum of heterogeneity in the dynamic enhancement pattern within the tumor. The quantity of low-enhancement regions (10th percentile RSI < 2.5) significantly predicted subsequent tumor recurrence (88% vs. 0%, P = 0.0004). Discriminant analysis based on both 10th percentile RSI and pixel number (reflective of tumor size) further improved the prediction rate (100% correct prediction of subsequent tumor control vs. recurrence). These preliminary results suggest that quantification of the extent of poor vascularity regions within the tumor may be useful in predicting long-term tumor control and treatment outcome in cervical cancer. J. Magn. Reson. Imaging 2000;12:1027-1033.

Aged↗

Laryngeal cancer cost analysis: association of case-mix and treatment characteristics with medical charges.

OBJECTIVES: To examine the relationship of various pretreatment case-mix characteristics and treatment modalities with medical charges incurred during diagnosis, treatment, and 2-year follow-up for patients with laryngeal cancer. DESIGN: Retrospective chart review and billing record analysis. METHODS: The charts and billing records of patients diagnosed with laryngeal cancer at the University of Iowa Hospitals and Clinics (UIHC) between January 1, 1991 and December 31, 1994 were reviewed. The independent variables included various pretreatment patient-mix and tumor characteristics (age, AJCC TNM clinical stage, smoking history, ASA class, and comorbidity as defined by Kaplan-Feinstein grade) as well as type of treatment. The dependent variables included total physician, office, and university hospital-based charges incurred during the pretreatment evaluation and 0- to 3-, 3- to 12, and 12- to 24-month billing periods after the initiation of cancer-directed therapy. Total 1-year and 2-year charges were also evaluated. Univariate and multivariate analyses were used to investigate the relationships between dependent and independent variables and to develop models predictive of management charges during the individual and total billing periods. RESULTS: Pretreatment charges showed no significant associations (P < .05) with any of the independent variables. Multiple regression analyses indicated that comorbidity, stage, and initial treatment modality were significant variables in one or more of the models predicting charges incurred during the 0- to 3-month, 3- to 12-month, total 1-year, and total 2-year billing periods. The models yielded R2 values for the total 1- and 2-year billing periods of 0.5246 and 0.5055, respectively. CONCLUSIONS: This work supports continued study of measures that may result in earlier detection of laryngeal cancer as a potential means of reducing management charges. These results also indicate that a more accurate method of stratifying the disease severity of laryngeal cancer patients for reimbursement purposes would include measurements of the severity of the index disease as well as comorbid diseases.

Aged↗

Synthesis and amyloid binding properties of rhenium complexes: preliminary progress toward a reagent for SPECT imaging of Alzheimer's disease brain.

The definitive diagnosis of Alzheimer's disease (AD) requires the detection of amyloid plaques in postmortem brain. Although the amount of fibrillar amyloid roughly correlates with the severity of symptoms at the time of death, the temporal relationship between amyloid deposition, neuronal loss, and cognitive decline is unclear. To elucidate this relationship, a noninvasive, practical method for the quantitation of brain amyloid deposition is required. We describe herein the initial stages of a strategy to accomplish this goal by single photon computed tomographic imaging. The amyloid-binding dye Congo Red was modified to allow its conjugation to the monoamine-monoamide bis(thiol) ligand. This ligand complexes technetium(V) in its neutral oxo form. A biphenyl-containing building block was conjugated to the protected ligand, and the product was coupled to the relevant aromatic compounds. Rhenium oxo complexes, which are isosteric, but nonradioactive, analogues of the potential imaging agent technetium oxo complexes, were synthesized. These complexes bound to Abeta amyloid fibrils produced in vitro and stained amyloid plaques and vascular amyloid in AD brain sections.

Alzheimer Disease↗

Studies on the antitumor activity and biochemical actions of cyclopentenyl cytosine against human colon carcinoma HT-29 in vitro and in vivo.

Cyclopentenyl cytosine (CPEC) is cytotoxic to several tumor cell lines. CPEC inhibits CTP synthesis resulting in depletion of cytidylate pools. The aim of this study was to examine CPEC's cytotoxic and antitumor activity in vitro and in vivo against human colon carcinoma HT-29, and to relate its action on CTP synthesis. CPEC exhibits potent cytotoxicity in vitro to HT-29 cells with an LC50 (concentration that is lethal to the survival of 50% cell colonies) of 2.4 microM and 0.46 microM following 2 h and 24 h exposure, respectively. Incubation of cells with CPEC for 2 h resulted in a dose-dependent decrease in cytidylate pools. The in vivo antitumor activity of CPEC in athymic mice transplanted subcutaneously (s.c.) with 3 million HT-29 cells was examined. Antitumor activity of CPEC was elucidated in early-staged tumor, wherein CPEC (1.5 mg/kg, QD x 9 or 3 mg/kg, QOD x 9) was administered intraperitoneally (i.p.) 24 h after tumor implantation and it resulted in a significant reduction in tumor weight to 48% of control. The effect of CPEC on established solid tumors in vivo was examined in athymic mice transplanted s.c. 14 days earlier with HT-29 cells and treated i.p. with 1.5 mg/kg CPEC, QD x 5 for 4 courses, with a 10 day-interval between courses. This treatment resulted in a significant reduction in tumor weight (72%) in the treated group. HPLC analysis of HT-29 tumor obtained from mice after treatment with CPEC showed a depletion of the CTP concentration reaching a nadir at 8 h. In conclusion, the present studies demonstrate potent antitumor activity of CPEC against freshly transplanted and established human colon carcinoma which can be corroborated with the drug's biochemical actions.

Adenosine Triphosphate↗

Radiation field simulation of gynecologic malignancies: localization of the cervix and vagina with a flexible vaginal localizer contrast tampon.

The authors evaluated a flexible vaginal localizer contrast tampon for radiation therapy simulation. In 51 patients, the degree of cervical or vaginal cuff displacement secondary to the contrast tampon was evaluated by comparing simulation radiographs (with tampon) and initial portal radiographs (without tampon). The same comparisons were made on the radiographs obtained in 25 control subjects who underwent simulation without a tampon. Mean displacement in the group who underwent simulation with a tampon was minimal (< or = 5 mm in each direction) and similar to that in the control group. This technique provides reliable cervical and vaginal cuff localization.

Brachytherapy↗

The use of laminarias for osmotic dilation of the cervix in gynecological brachytherapy applications.

PURPOSE: Osmotic dilators (laminarias) have been used for gradual nontraumatic dilation of the cervical canal for various intrauterine procedures; however, this technique has not been well accepted in gynecological brachytherapy. The purpose of this study was to evaluate the efficacy of osmotic cervical dilation for brachytherapy in gynecologic cancer patients, without the use of general/regional anesthesia, and to assess patient tolerance, complications, and outcome. METHODS AND MATERIALS: Thirteen brachytherapy procedures were performed in 6 patients with clinical Stages I and II endometrial (5) and Stage IB cervical cancer (1), who were unable to tolerate general/regional anesthesia because of severe medical problems. An osmotic dilator (synthetic laminaria) was inserted into the cervical os 10-12 h before each brachytherapy procedure and removed just before the procedure. Standard Fletcher-Suit-Delclos tandem insertions with vaginal colpostats or cylinders were then performed. Degree of cervical dilation, patient discomfort, procedure time, intra- and postoperative complications were recorded, and local control and survival were assessed. Median follow-up was 31 months (range: 8-35 months). RESULTS: The diameter of the dilated cervical os after laminaria removal was adequate (> or = 5 mm) for tandem insertion, and no additional mechanical dilation was required in all but one procedure (1 of 13). All procedures were performed without general/regional anesthesia. The mean duration of the procedures was 44 min (range, 20-60 min). Discomfort was minimal in all cases. There were no intra- or postoperative complications. All patients maintained local control until death (1 of metastatic disease, 2 of intercurrent disease) or last follow-up (2 with no evidence of disease, 1 alive with metastatic disease). CONCLUSION: This preliminary study suggests that osmotic cervical dilation with a synthetic laminaria is a useful technique to facilitate intrauterine tandem insertion in patients who cannot tolerate general/regional anesthesia. This technique may reduce treatment-associated morbidity, shorten procedure time, and allow the delivery of adequate radiation therapy in this uncommon but challenging patient population.

Adenocarcinoma↗

NACP, a protein implicated in Alzheimer's disease and learning, is natively unfolded.

The "non-A beta component of Alzheimer's disease amyloid plaque" (NAC) is a minor peptide component of the insoluble fibrillar core of the Alzheimer's disease (AD) neuritic plaque. NAC amyloid fibrils seed the polymerization of A beta 1-40, the major AD amyloid protein. NAC is derived from a 14 kDa precursor protein, designated NACP, a member of a highly conserved family of heat-stable brain-specific acidic proteins which have been suggested to be involved in synapse formation and/or stabilization. NACP has also been suggested to play a role in AD. We present herein a conformational analysis of human NACP. NACP has a much larger Stokes radius (34 A) but sedimented more slowly (s20,w = 1.7S) than globular proteins of similar molecular weight, indicating that the native protein is elongated. Circular dichroism (CD) and Fourier-transform infrared spectroscopy (FTIR) indicate the absence of significant amounts of secondary structure in NACP, while CD and ultraviolet spectroscopy suggest the lack of a hydrophobic core. The conformational properties of NACP were unchanged by boiling and were independent of concentration, pH, salt, and chemical denaturants. These features indicate that NACP exists as a mixture of rapidly equilibrating extended conformers and is representative of a class of "natively unfolded" proteins, many of which potentiate protein-protein interactions.

Alzheimer Disease↗

[The role nitric oxide and other neurotransmitter in canine penile erection].

The role on nitric oxide and its relative factors (cGMP, cAMP, methylene blue) was studied in canine erection induced by stimulating pelvic nerves, and the effect of cholinergic neuroeffectors and the sinusoidal endothelium was also observed in this experiment. The results indicate that intracavernous injection of nitric oxide can evoke a penile tumescence, which is similar to that of the neurostimulation. The results also suggest that the cholinergic nerves and the sinusoidal endothelium are involved in erection, and the effect of the former must depend on mediation of the latter. The study supports that cholinergic and nonadrenergic noncholinergic (NANC) neuroeffectors take part in penile erection, and nitric oxide may be one of chief NANC neurotransmitters.

Animals↗