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PubMed2006

8-Isoprostane is a dose-related biomarker for photo-oxidative ultraviolet (UV) B damage in vivo: a pilot study with personal UV dosimetry.

BACKGROUND: Ultraviolet (UV) B irradiation causes visible erythema, which has been linked with DNA damage. However, besides such direct photochemical conformation changes, UVB also induces many indirect photochemical effects in the skin. Lipid peroxidation (LPO) is in this context one of the major pathways by which photo-oxidative stress disturbs cell signalling and promotes photocarcinogenesis and photoageing. So far we lack techniques for visualizing photo-oxidative stress in the skin. Furthermore, LPO has never been linked with individually acquired UVB doses measured by personal dosimetry. OBJECTIVES: Measuring the skin reaction and photo-oxidative damage by LPO in vivo after UVB exposure in a pilot study surveyed by personal dosimetry in order to allow for a correlation analysis of acquired dose, skin reaction and amount of LPO. METHODS: UVB exposure was measured with the opto-electronic X2000-1 (Gigahertz Optik, Puchheim, Germany) and the biological DLR Biofilm (German Aerospace Center DLR, Cologne, Germany) portable dosimeter. The skin reaction following UVB exposure was quantified with a Minolta chromameter (Minolta, Tokyo, Japan) and LPO in vivo was measured by 8-isoprostane generation by means of densitometric analysis of immunohistochemical samples obtained 30 min post-UVB irradiation. RESULTS: Regression analysis revealed significant linear relations between UVB exposures recorded by the dosimeters and colorimetry parameters of the skin reaction. Furthermore, an even better linear relation with higher significance was found between the generation of 8-isoprostane in the skin and the dosimeter readouts. CONCLUSIONS: LPO measured by the generation of 8-isoprostane provides a suitable intrinsic biomarker for photo-oxidative UVB damage in vivo. This study provides a new approach to visualizing photo-oxidative stress in the skin in vivo. Furthermore, future dosimeter readouts can now be set into relation to the expected increase of LPO that can be calculated within the limits of our study.

Adult↗

PubMed2003

Clinical significance of 3D reconstruction of arteriovenous malformation using digital subtraction angiography and its modification with CT information in stereotactic radiosurgery.

PURPOSE: A three-dimensional (3D) reconstruction method of arteriovenous malformation (AVM) nidus from digital subtraction angiography (DSA) in combination with CT and/or MRI was developed, and its usefulness was evaluated in this study. MATERIALS AND METHODS: The contour of the AVM nidus was delineated on two orthogonal projected DSA images. First, the volume and center of the AVM nidus were calculated in a classic DSA plan using three maximal lengths of the nidus in three perpendicular directions, assuming that the nidus had a prolate ellipsoid shape. Second, in the 3D-DSA plan, the contours of the AVM nidus on the two orthogonal projected DSA images were segmented to be compatible with the slice thickness of the CT image. Assuming that each segment of the nidus has an ellipsoid pillar shape, the volume and center of each segment were calculated. The volume and 3D shape of the nidus were calculated by 3D reconstruction in the 3D-DSA plan. Third, in the CT-DSA plan, the contour based on the segmented DSA was superimposed on the corresponding transaxial CT image slice by slice. The cylindrical shape of the nidus in the transaxial image was modified using the enhanced CT images in the CT-DSA plan. These three planning methods were compared using dose-volume statistics from real patients' data. Eighteen patients with intracranial AVMs in different brain locations who had been treated by radiosurgery were the subjects of this study. To examine the visibility (validity) of the nidus on the CT image, the "nidus" was delineated on an enhanced CT image without DSA superposition in the CT plan and compared with the CT-DSA plan. RESULTS: The variance in the distance between coordinates determined by the CT plan and those determined by the classic DSA plan was significantly larger than the variance in the CT-DSA plan (p < 0.0001 for lateral, AP, and craniocaudal directions). The difference in the variance was not reduced by the addition of MRI (p < 0.0001 for each direction). The mean volume +/- SD of the nidus calculated was 5.9 +/- 8.0 cm(3) in the classic DSA plan, 4.0 +/- 5.6 cm(3) in the 3D-DSA plan, and 3.6 +/- 5.2 cm(3) in the CT-DSA plan. The 3D-DSA plan significantly reduced the mean nidus volume 31.8% +/- 12.7% from the classic DSA plan (p = 0.0054). The CT-DSA plan further significantly reduced the volume 9.8% +/- 8.8% from the 3D-DSA plan (p = 0.0021). The mean overlapping volume of the nidus between the CT plan and CT-DSA plan was 2.6 +/- 4.3 cm(3) (range 0.17-18.9), corresponding to 63.7% +/- 19.2% (range 11.4-85.3%) of the volume in the CT-DSA plan. CONCLUSIONS: The superposition of the segmented DSA information on CT was shown to be an important tool to determine the precise shape of the nidus and is suggested to be useful to reduce partial occlusion of the AVM or radiation complications in radiosurgery.

Adolescent↗

PubMed1996

Improved survival in stage III non-small-cell lung cancer: seven-year follow-up of cancer and leukemia group B (CALGB) 8433 trial.

BACKGROUND: For many years, high dose radiation therapy was the standard treatment for patients with locally or regionally advanced non-small-cell lung cancer (NSCLC), despite a 5-year survival rate of only 3%-10% following such therapy. From May 1984 through May 1987, the Cancer and Leukemia Group B (CALGB) conducted a randomized trial that showed that induction chemotherapy before radiation therapy improved survival during the first 3 years of follow-up. PURPOSE: This report provides data for 7 years of follow-up of patients enrolled in the CALGB trial. METHODS: The patient population consisted of individuals who had clinical or surgical stage III, histologically documented NSCLC; a CALGB performance status of 0-1; less than 5% loss of body weight in the 3 months preceding diagnosis; and radiographically visible disease. Patients were randomly assigned to receive either 1) cisplatin (100 mg/m2 body surface area intravenously on days 1 and 29) and vinblastine (5 mg/m2 body surface area intravenously weekly on days 1, 8, 15, 22, and 29) followed by radiation therapy with 6000 cGy given in 30 fractions beginning on day 50 (CT-RT group) or 2) radiation therapy with 6000 cGy alone beginning on day 1 (RT group) for a maximum duration of 6-7 weeks. Patients were evaluated for tumor regression if they had measurable or evaluable disease and were monitored for toxic effects, disease progression, and date of death. RESULTS: There were 78 eligible patients randomly assigned to the CT-RT group and 77 randomly assigned to the RT group. Both groups were similar in terms of sex, age, histologic cell type, performance status, substage of disease, and whether staging had been clinical or surgical. All patients had measurable or evaluable disease at the time of random assignment to treatment groups. Both groups received a similar quantity and quality of radiation therapy. As previously reported, the rate of tumor response, as determined radiographically, was 56% for the CT-RT group and 43% for the RT group (P = .092). After more than 7 years of follow-up, the median survival remains greater for the CT-RT group (13.7 months) than for the RT group (9.6 months) (P = .012) as ascertained by the logrank test (two-sided). The percentages of patients surviving after years 1 through 7 were 54, 26, 24, 19, 17, 13, and 13 for the CT-RT group and 40, 13, 10, 7, 6, 6, and 6 for the RT group. CONCLUSIONS: Long-term follow-up confirms that patients with stage III NSCLC who receive 5 weeks of chemotherapy with cisplatin and vinblastine before radiation therapy have a 4.1-month increase in median survival. The use of sequential chemotherapy-radiotherapy increases the projected proportion of 5-year survivors by a factor of 2.8 compared with that of radiotherapy alone. However, inasmuch as 80%-85% of such patients still die within 5 years and because treatment failure occurs both in the irradiated field and at distant sites in patients receiving either sequential chemotherapy-radiotherapy or radiotherapy alone, the need for further improvements in both the local and systemic treatment of this disease persists.

Antineoplastic Agents, Phytogenic↗

PubMed2002

Electronic procedure logs: taking it further.

OBJECTIVE: To create an electronic procedural logbook with enhanced user interactivity and usefulness as an educational resource. DESCRIPTION: From our own work on electronic student logbooks and other studies, it is clear that compliance with complete and valid data entry remains a challenge. Without direct and visible benefit, students are reluctant to spend time logging all their cases. We developed an interactive procedural logbook using Microsoft Embedded Visual Basic and Metrowerks CodeWarrior. Interface design focused on rapid data entry with minimum requirement for text, and field-level automation where possible. We loaded it onto a mixed platform of personal digital assistants (PDAs)--Compaq iPaq Pocket PCs and HandEra 330 PalmOS devices. Our rural residents were supplied with the devices of their choice. Various built-in educational reference resources included: (1) contextual help options about each procedure, which contained diagrams and pictures; (2) diagnostic and fee coding so they could see how poorly some procedures pay; and (3) Quick Tips relevant to each procedure, which can be easily modified by the preceptor. Preceptor evaluations and comments can be entered rapidly. Using built-in database conduits, data are automatically collected from each device on every HotSync with the desktop. Data can then be collated and analyzed using Microsoft Access or via secure Web access. DISCUSSION: Improved compliance has been dramatic-one resident logged 250 procedures in just two months. However, not all residents have been successful in establishing seamless synchronization, and the resulting data loss has caused frustration. The evidence indicates the need to implement central data collection and backup right from the outset. Central data collection provides many advantages. The program director has better information for future applications. Preceptor evaluations are now spread over many interactions and yet can be collated and analyzed. Quick Tips have been very popular-we have been able to collect the tips and redistribute them. Focus-group feedback from the residents has shown that the rich data in the logbook's reference component improved its usefulness and popularity as an educational tool. Choice of device type is important for user acceptance because devotees of one platform are reluctant to switch to another. Cross-platform development does slow the process but is increasingly easy with the latest software design tools, such as AppForge. These new tools have enabled us to explore further improvements in data entry. Digital ink provides the ability to capture annotated diagrams and preceptor signatures. Voice input is built in with these devices, and our software now allows for voice annotation for more detailed commentary by preceptors or student. The compressed digital sound file is collected along with the data and transcribed centrally (on-device voice recognition is not feasible yet). Point-of-care accessibility has been the key attraction of using these devices for logging encounter data. This project demonstrates that it is important to explore all multimodal interactive capabilities to provide a truly rich educational tool.

Electronic Data Processing↗

PubMed1986

A new visible light-cured resin system applied to removable prosthodontics.

Preliminary studies of VLC resins have produced promising results; however, additional research is necessary to completely define qualities of this material. Biologic testing of VLC (Triad) resins indicated that they are nontoxic and biocompatible. They have a wide range of uses in all subdisciplines of prosthodontics. Advantages such as accuracy of fit, superior strength, complete polymerization without residual compounds, ease of fabrication and manipulation, patient acceptance, ability to bond with other denture base resins, and low bacterial adherence make this material an important addition to the choices available to dentists. As with many new materials, there are initial problems or hurdles that must be overcome before there is widespread use. Initial formulations of material had insufficient flexural strength and tended to fracture when flexed over uncut sites on a stone cast. This problem has been reduced by Dentsply International, Inc. with the introduction of the new improved formulation. The original VLC bonding agent did not provide sufficient bond strength with acrylic resin denture base materials, but this also has been improved with development of a new VLC bonding agent. The problem of microporosity and small voids produced when adapting VLC resin sheets against a stone cast may be overcome with pressure or vacuum adaptation techniques. A promising application of VLC resin material is in direct intraoral procedures such as relining of dentures. Physical and chemical properties are superior to autopolymerizing methacrylates. Preliminary studies have shown successful patient acceptance to this clinical procedure. It is of particular advantage to the patient not to be without dentures for the period of at least 1 day necessary for a laboratory-processed relining. Immediate light-curing is time-saving and convenient compared to indirect (heat-cured) relining. Until recently, most direct intraoral applications of autopolymerizing acrylic resin reliner material were considered temporary or expedient to a permanent procedure. The patient and dentist may now have another treatment choice. The release of residual methyl methacrylate, among other shortcomings of AP materials, is not a concern when using the VLC reliner material. Some patients may notice a nonobjectionable taste to the uncured material; however, they can be reassured that the taste will be only temporary until the material is completely polymerized in the curing unit. The flow of the material can be regulated by selection of appropriate viscosity, warming and cooling measures, and partial intraoral polymerization with hand-held curing lights.(ABSTRACT TRUNCATED AT 400 WORDS)

Acrylic Resins↗

PubMed1998

Recanalization therapies for acute ischemic stroke.

Angiographic studies performed within 6 hours of stroke onset have demonstrated that 75-80% of patients with an acute ischemic stroke have an angiographically visible occlusion of an extracranial and/or intracranial artery that is the cause of the ischemic stroke. The NINDS t-PA Stroke Study demonstrated that recanalization of occluded brain arteries can successfully salvage ischemic brain if intravenous tissue plasminogen activator (t-PA) is initiated within 3 hours of stroke onset. The effectiveness and safety of intravenous t-PA beyond 3 hours has yet to be shown. Large clots in the internal carotid artery, vertebral or basilar artery, or middle cerebral artery trunk are infrequently lysed by intravenous t-PA during the first hour of treatment. Intraarterial delivery of a thrombolytic agent appears to lyse clots in cerebral arteries more effectively than intravenous t-PA. However, a head-to-head comparison of full-dose intravenous t-PA and intraarterial therapy has yet to be done, and recanalization rates reported in the intraarterial studies are at longer times after the start of therapy than the rates of recanalization reported in intravenous t-PA studies. Intraarterial delivery of thrombolytic therapy takes longer than intravenous delivery, and even intraarterial delivery takes 2 hours on average to partially or completely lyse 75% of clots. Intraarterial delivery of a thrombolytic agent has yet to be proven effective and safe in improving long-term outcome of ischemic stroke patients. The approach of combining intravenous and intraarterial delivery of t-PA or other pharmacologic agents is an attractive option that deserves further study. Mechanical lysis of clots, in combination with pharmacologic therapies, is a more effective way to recanalize coronary arteries and salvage heart muscle than intravenous thrombolytic therapy alone. This approach is likely to be effective in ischemic stroke as well. What is needed is advances in catheter technology that meet the special requirements of clot lysis in cerebral vessels. Whether neuroprotective agents can extend the therapeutic window for effective clot lysis and recanalization remains to be seen. Thrombolytic therapy and other pharmacologic treatments of clot in cerebral vessels will likely remain a two-edged sword. Pharmacologic therapies that increase the likelihood of clot lysis and recanalization, such as thrombolytic agents, the platelet GIIbIIIa receptor blockers, defibrinogenating agents, and even the newer more potent thrombolytic agents, also concomitantly increase the risk of bleeding into the brain. What we will be searching for in the coming decade is the correct mechanical strategy, dose of a given pharmacologic agent, or combination of agents that maximizes recanalization and minimizes the risk of intracerebral hemorrhage.

Angioplasty, Balloon↗

PubMed2000

Improving the dosimetric coverage of interstitial high-dose-rate breast implants.

PURPOSE/OBJECTIVE: We performed a retrospective computed tomography (CT)-based three-dimensional (3D) dose-volume analysis of high-dose-rate (HDR) interstitial breast implants to evaluate the adequacy of lumpectomy cavity coverage, and then designed a simple, reproducible algorithm for dwell-time adjustment to correct for underdosage of the lumpectomy cavity. METHODS AND MATERIALS: Since March 1993, brachytherapy has been used as the sole radiation modality after lumpectomy in selected protocol patients with early-stage breast cancer treated with breast-conserving therapy. In this protocol, all patients received 32 Gy in 8 fractions of 4 Gy over 4 days. Eleven patients treated with HDR brachytherapy who underwent CT scanning after implant placement were included in this analysis. For each patient, the postimplant CT dataset was transferred to a 3D treatment planning system, and the relevant tissue volumes were outlined on each axial slice. The implant dataset, including the dwell positions and dwell times, were imported into the 3D planning system and then registered to the visible implant template in the CT dataset. The calculated dose distribution was analyzed with respect to defined volumes via dose-volume histograms. Due to the variability of lumpectomy cavity coverage discovered in this 3D quality assurance analysis, dwell times at selected positions were adjusted in an attempt to improve dosimetric coverage of the lumpectomy cavity. Using implant data from 5 cases, a dwell-time adjustment algorithm was designed and was then tested on 11 cases. In this algorithm, a point P was identified using axial CT images, which was representative of the underdosed region within the cavity. The distance (d) from point P to the nearest dwell position was measured. A number of dwell positions (N) nearest to point P were selected for dwell time adjustment. The algorithm was tested by increasing the dwell times of a variable number of positions (N = 1, 3, 5, 7, 10, and 20) by a weighting factor (alpha), where alpha = f(d) and alpha > 1, and subsequently performing 3D dose-volume analysis to evaluate the improvement in lumpectomy cavity coverage. RESULTS: Before adjustment in the 11 implants, the median proportion of the lumpectomy cavity and target volume that received at least the prescription dose was 85% and 68%, respectively. After dwell-time adjustment, lumpectomy cavity coverage was significantly improved in all 11 cases. The median distance from point P to the nearest dwell position (d) was 1.4 cm (range 0.9-1.9). The median volume of the lumpectomy cavity receiving 32 Gy increased from 85.3% in the actual implant to 97.0% (range 74-100%) by increasing the dwell time of a single dwell position by a median factor (alpha) of 12.2 according to the above algorithm. With N = 3, the median proportion of the cavity volume receiving 32 Gy was improved to 97.5% (range 77-100%), with a median alpha of 5.7. Further improvement in lumpectomy cavity coverage was relatively small by increasing additional dwell times. In addition, with N = 20, the median absolute volume of breast tissue receiving 150% of the prescription dose was 70.3 cm3 compared to 26.3 cm3 in the actual implant; whereas with N = 1 or N = 3, this median volume was only 35.9 and 42.0 cm3, respectively. CONCLUSION: Lumpectomy cavity coverage sometimes appears suboptimal with interstitial HDR breast brachytherapy using our current technique. A simple dwell-time increase at only 1-3 dwell positions can compensate for some underdosage without creating significant regions of overdosage. Using simple methodology, a single reference point representing the underdosed region can be utilized for initial selection of the dwell positions to be increased.

Algorithms↗

PubMed1997

Prostate carcinoma screening in the county of Tyrol, Austria: experience and results.

BACKGROUND: This article summarizes the experience and results of different prostate carcinoma screening projects using total prostate specific antigen (PSA) as the initial test and different diagnostic tests to improve specificity. METHODS: The seven projects studied included 1) a mass screening study using PSA as the initial test in 21,079 volunteers; 2) an investigation of the usefulness of normal and age-referenced PSA cutoffs in 1618 men; 3) a PSA-based screening study of 2272 asymptomatic blood donors; 4) an investigation of the incidence and clinical significance of transitional zone carcinoma in 340 men with negative rectal examination findings and clearly visible prostatic zones on three-dimensional transrectal ultrasound; 5) determination of percent free PSA in one retrospective and two prospective screening studies to define the optimal range of total PSA and determine the appropriate cutpoints for percent free PSA within this range; 6) evaluation of the diagnostic benefit of PSA transitional zone density in 308 screening volunteers; and 7) a study of the impact of PSA-based screening on the percentage of incidental prostate carcinoma diagnosed in 1543 men undergoing transurethal resection of the prostate. RESULTS: 1) Of the 21,078 volunteers, 1618 (8%) had elevated PSA levels. Of these men, 778 (48%) underwent biopsies; 197 biopsies (25%) were positive for prostate carcinoma and 135 patients underwent radical prostatectomy. Ninety-five of the 135 pathologically staged lesions (70%) were found to be organ-confined. 2) A PSA cutoff of 2.5 ng/mL in men age 45-49 years and of 3.5 ng/mL in men age 50-59 years with normal digital rectal examination findings resulted in an 8% increase in both the number of biopsies (66 of 778) and the detection rate of organ-confined disease. 3) Of the 2272 men, 284 had elevated PSA levels and prostate carcinoma was detected in 62 men. All patients underwent radical prostatectomy and histologic examination revealed organ-confined disease in all but eight men. 4) Ninety-eight of 340 men (28.8%) had biopsies positive for carcinoma; 28 of these patients (28.5%) had carcinoma that originated in the transitional zone only. 5) In the retrospective study, receiver operating characteristic curve analysis showed that by using a percent free PSA of 18% as a biopsy criterion in men with an elevated PSA serum level, 37% of the negative biopsies could be eliminated although 94% of all carcinomas would still be detected. In the first prospective study, 106 of 158 men with elevated total PSA values between 2.5 and 10.0 ng/mL were further evaluated and 37 prostate carcinomas were detected. By using a percent free PSA of < or =22% as a biopsy criterion, 30% of the negative biopsies could be eliminated although 98% of the carcinomas would still be detected. In the second prospective study, 120 of 465 men with total PSA levels between 1.25 and 6.49 ng/mL, a percent free PSA of <18%, and normal digital rectal examination findings were further evaluated and 27 (22.5%) were found to have prostate carcinoma. 6) Receiver operating characteristic curve analysis for PSA transitional zone density showed that by using a PSA transitional zone density of >0.22 ng/mL/cc as a biopsy criterion, 24.4% of negative biopsies could be avoided without missing the detection of a single carcinoma. 7) In the prescreening era the incidence of T1a Grade 1 and 2 carcinomas was 3.1% and the incidence of T1a Grade 3 and T1b carcinoma was 2.3%, whereas in the years after the establishment of PSA-based screening the incidence was 4.6% and 1.03%, respectively. CONCLUSIONS: These data suggest that PSA-based screening increases the detection rate of clinically significant and organ-confined tumors. Percent free PSA and PSA transitional zone density provide an additional diagnostic benefit over total PSA.

Age Factors↗

PubMed2002

Radiosurgery for residual or recurrent nonfunctioning pituitary adenoma.

OBJECT: Nonfunctioning pituitary adenomas comprise approximately 30% of all pituitary tumors. The purpose of this retrospective study is to evaluate the efficacy and role of gamma knife radiosurgery (GKS) in the management of residual or recurrent nonfunctioning pituitary adenomas. METHODS: A review was conducted of the data obtained in 42 patients who underwent adjuvant GKS at the University of Pittsburgh between 1987 and 2001. Prior treatments included transsphenoidal resection, craniotomy and resection, or conventional radiotherapy. Endocrinological, ophthalmological, and radiological responses were evaluated. The duration of follow-up review varied from 6 to 102 months (mean 31.2 months). Fifteen patients were observed for more than 40 months. The mean radiation dose to the tumor margin was 16 Gy. Conformal radiosurgery planning was used to restrict the dose to the optic nerve and chiasm. Tumor control after GKS was achieved in 100% of patients with microadenomas and 97% of patients with macroadenomas. Gamma knife radiosurgery was equally effective in controlling adenomas with cavernous sinus invasion and suprasellar extension. No patient developed a new endocrinological deficiency following GKS. One patient's tumor enlarged with an associated decline in visual function. Another patient experienced a deterioration of visual fields despite a decrease in tumor size. CONCLUSIONS: Gamma knife radiosurgery can achieve tumor control in virtually all residual or recurrent nonfunctioning pituitary adenomas. Dose sparing facilitates tumor management even when the adenoma is close to the optic apparatus or invades the cavernous sinus.

Adenoma↗

PubMed2000

Gamma knife radiosurgery as a primary treatment for prolactinomas.

OBJECT: The purpose of this study was to estimate the efficacy of gamma knife radiosurgery (GKS) in controlling tumor growth and endocrinopathy associated with prolactinomas. METHODS: Between 1993 and 1997, 164 of 469 patients with pituitary adenomas treated by GKS harbored prolactinomas. The dose to the tumor margin ranged from 9 to 35 Gy (mean 31.2 Gy), and the visual pathways were exposed to a dose of less than 10 Gy. The mean tumor diameter was 13.4 mm. The mean follow-up time for 128 cases was 33.2 months (range 6-72 months). Tumor control was observed in all but two patients who underwent surgery 18 and 36 months, respectively, after GKS. Clinical cure was achieved in 67 cases. Clinical improvement was noted with a decrease in the hyperprolactinemia after GKS. Nonetheless, in 31 (29%) of 108 patients who were followed for more than 2 years no improvement in serum prolactin levels was demonstrated, although this could be normalized by bromocriptine administration after treatment. Nine infertile women became pregnant 2 to 13 months after GKS and all gave birth to normal children. There was no visual deterioration related to GKS. Five women experienced premature menopause. In these patients there was subtotal disappearance of the tumor and an empty sella developed. CONCLUSIONS: Gamma knife radiosurgery as a primary treatment for prolactinomas can be safe and effective both for controlling tumor growth and for normalization of prolactin hypersecretion. A higher margin dose (> or = 30 Gy) seemed to be associated with a better clinical outcome. Gamma knife radiosurgery may make prolactinomas more sensitive to the bromocriptine.

Humans↗