Imaging of external instabilities of the patella. State of the art

Recent articles in the scientific literature have described major advances in our understanding of the anatomy and vascular relationships of the optic nerve (cranial nerve II) and of the diagnosis and treatment of a variety of disorders affecting this nerve, including congenital anomalies of the optic disc, dominant hereditary optic neuropathy, anterior and retrobulbar arteritic and nonarteritic ischemic optic neuropathy, optic neuritis, Cuban epidemic optic neuropathy, toxic and nutritional optic neuropathies, radiation-induced optic neuropathy, AIDS-related optic neuropathy, optic neuropathies caused by tumors, and papilledema.     

Endothelin in migraine patients

AIM: Improvement of the dose homogeneity in radiation treatment of the intact breast using 3D-planning and dose volume histograms. PATIENTS AND METHOD: 3D-planning, including the calculation of dose volume histograms of the planning target volume, was performed on 15 patients, who underwent radiation therapy with tangential photon beams. A standard plan and 2 modified or optimized plans were evaluated. Different dosimetric parameters like maximum dose, mean dose, standard deviation and the fractional volume which receives doses from 95 to 105% of the reference dose were compared and correlated with breast size. RESULTS: With increasing breast size standard planning leads to increased overdosage, both in magnitude and volume. Individual optimization by modifying weights and wedges gives no improvement in dose homogeneity, whereas a photon energy of 10 MV results in a more homogeneous dose distribution. The drawback of the higher energy is the increased underdosage of the skin. CONCLUSION: Using the standard geometry of tangential fields the dose homogeneity cannot be improved significantly by 3D-planning, compared to our standard technique.     

Radiation optic neuropathy after stereotactic radiosurgery

PURPOSE: The purpose of the study is to report the occurrence of optic neuropathy after stereotactic radiosurgery for perichiasmal tumors. METHODS: Records of four patients with visual deterioration after stereotactic radiosurgery were reviewed, including clinical findings, neuroimaging results, and treatment methods. RESULTS: Optic neuropathy developed 7 to 30 months after gamma knife radiosurgery. All patients experienced an abrupt change in visual function. Clinical findings indicated anterior visual pathway involvement. Patterns of field loss included nerve fiber bundle and homonymous hemianopic defects. Gadolinium-enhanced magnetic resonance imaging (MRI) showed swelling and enhancement of the affected portion of the visual apparatus in three patients. Systemic corticosteroids were administered in all patients and one partially recovered. One patient also received hyperbaric oxygen without improvement. CONCLUSIONS: Although rare, optic neuropathy may follow radiosurgery to lesions near the visual pathways. Careful dose planning guided by MRI with restriction of the maximal dose to the visual pathways to less than 8 Gy will likely reduce the incidence of this complication.     

Ulcer in the oral mucosa of torpid course and conjunctival injection]

We report two cases of presumed radiation-induced brachial plexus neuropathy in patients with lymphoma who were treated with standard mantle radiotherapy to a dose of 40 Gy in 20 fractions. Radiation-induced brachial plexopathy has not previously been reported following mantle irradiation at this dose. Both patients received chemotherapy in relapse. We postulate three possible causes: enhanced radiation sensitivity; an interaction between the chemotherapy and the radiotherapy; or an increased dose in axilla owing to a smaller separation at that point.     

Potentiation of radiation-induced regrowth delay in murine tumors by fludarabine

Fludarabine (9-beta-D-arabinofuranosyl-2-fluoroadenine-5'-monophosphate), an adenine nucleoside analogue, has previously been shown to inhibit the repair of radiation-induced chromosome damage. Thus fludarabine may have therapeutic utility in combination with photon irradiation. The purpose of this study was to determine whether fludarabine could enhance radiation-induced murine tumor regrowth delay and to determine the most effective dose and schedule of the combination. A significant (P < 0.05) absolute regrowth delay enhancement was observed in three murine tumor models (SA-NH, a sarcoma; and MCA-K and MCA-4, mammary carcinomas) when fludarabine (800 mg/kg) was given 1 h prior to 25 Gy gamma-irradiation. While fludarabine enhanced radiation-induced tumor regrowth delay when given between -36 h and +6 h of radiation (SA-NH tumor), the greatest enhancement was observed when fludarabine was given at -24 h prior to irradiation (radiation dose modification factor of 1.82 at -24 h compared to 1.57 at -3 h prior to radiation). The degree of fludarabine enhancement (at -3 or -24 h) was dose dependent at doses above 200 mg/kg. When fludarabine and radiation were administered on a fractionated schedule (fludarabine given 3 h prior to radiation each day for 4 days), the dose modification factor increased to 2.14 (1.63 if the effect of fludarabine alone is subtracted). These results suggest that fludarabine enhances radiation-induced tumor regrowth delay in a more than additive fashion after both single and fractionated treatments, and the degree of enhancement is dependent on the sequence and timing of administration, the fludarabine dose, and the tumor type. Thus, fludarabine may have clinical potential as a radiation enhancer in the treatment of solid tumors.     

Pentoxifylline suppression of TNF-alpha mediated axonal degeneration in the rabbit optic nerve

In AIDS patients, axonal degeneration in the optic nerve occurs as a histopathological manifestation of the optic neuropathy. Direct infection of neurons by HIV is unlikely, and the axonal injury may be an indirect effect mediated by cytotoxic factors such as tumor necrosis factor-alpha (TNF-alpha) which we have previously demonstrated to cause axonal degeneration in the rabbit optic nerve. To test the suppressive effects of pentoxifylline in preventing TNF-alpha-mediated axonal degeneration, we applied pentoxifylline to an established rabbit model that demonstrates an AIDS-like optic neuropathy using intravitreal TNF-alpha injections. Degenerated axonal profiles were numerous in control rabbit optic nerve (mean 1879) and reduced in rabbits receiving the medium dose of pentoxifylline (300 mg PO BID, mean 439, p < 0.001) and the highest dose of pentoxifylline (600 mg PO BID, mean 120, p < 0.007). High dose pentoxifylline reduced TNF-alpha-induced axonal losses to less than 10% that seen without pentoxifylline pretreatment. Lower doses of pentoxifylline had a lesser but significant protective effect. Our results suggest that TNF-alpha-mediated axonal degeneration can be suppressed by high doses of pentoxifylline. Pentoxifylline may therefore be useful in AIDS patients demonstrating neurological or neuro-ophthalmological symptoms.     

Conformal treatment planning for interstitial brachytherapy

PURPOSE: Quality of a brachytherapy application depends on the choice of the target volume, on the dose distribution homogeneity and radiation injury on critical tissue, which should be postulated by advanced brachytherapy treatment planning systems. MATERIAL AND METHODS: Basic imaging method for conformal treatment planning is the cross-sectional imaging. The clinical applicability of a new type 3D planning system using CT and/or MRT-simulation or US-simulation for planning purposes was studied. The planning system developed at Kiel University differs from usual brachytherapy planning systems because of the obligatory use of cross-sectional imaging as basic imaging method for reconstruction of structures of interest. Dose distribution and normal anatomy can be visualized on each CT/MRT/US slice as well as coronal, sagittal, axial and free chosen reconstruction (3D), as well as dose-volume histogram curves and special colour-coded visualization of dose homogeneity in the target can be analyzed. RESULTS: Because of the experience in the clinical routine, as well as on the base of 30 simultaneous planning procedures on both 2D (semi-3D) and 3D planning systems we observed similar time consumption. Advantages of 3D planning were the better interpretation of target delineation, delineation of critical structures as well as dose distribution, causing more accurate volume optimisation of dose distribution. CONCLUSION: Conformal brachytherapy treatment planning for interstitial brachytherapy means significant advantages for the clinical routine compared to 2D or semi-3D methods.     

Radiation dose in critical organs due to non-coplanar irradiation of the hypophysis

BACKGROUND: In order to estimate the somatic and genetic risk associated with a non-coplanar linac-based radiation technique of the pituitary gland, systematic secondary-dose measurements in a phantom and sample measurements of the dose near critical organs of patients were performed. PATIENTS AND METHODS: For measurements of the dose outside the primary radiation field an acrylic-PVC phantom was used which was irradiated with a single field (4 x 4 cm2). Eight patients with pituitary tumors were treated isocentrically with a combination of sagittal and transverse rotational arcs. To measure the dose in critical organs. LiF thermoluminescence dosimeters (TLD) in chip form were placed onto 1 eyelid, the skin over the thyroid, and the patient's clothes covering the region of breasts and ovaries of female patients and the testicles of male patients. Measurements were performed for all patients during 1 sagittal irradiation and for the majority of patients during 1 transverse irradiation. RESULTS: The phantom measurements demonstrated that the secondary dose measured on the patients surface can be considered as a good approximation for the dose in adjacent organs. The median dose in critical organs for sagittal irradiation was in the range of 25.8 mGy (eyes) to 1.9 mGy (testicles), and for transverse irradiation in the range of 23.3 mGy (eyes) to 1.3 mGy (testicles). The ratio of median organ doses for sagittal and transverse irradiation was 2.1 for the thyroid gland, 1.1 for the eyes, and 1.5 for the other organs. CONCLUSIONS: The dose in critical organs due to non-coplanar irradiation of the pituitary gland is only a small fraction of the dose delivered to the reference point of the planning target volume. The risk of a radiation-induced tumor and a genetic consequence associated with these small doses is generally less than 1% and 0.1%, respectively.     

Comparison of wound healing process using Argon and Krypton lasers

OBJECTIVE: We compared the wound healing process on Sprague-Dawley rats between Argon Laser and Krypton Laser, and calculated the laser actual doses after correction on wound healing on rats and estimated the clinical doses on wound healing for human skin. SUMMARY BACKGROUND DATA: Laboratory work provided some support for the use of low-intensity laser radiation in wound healing. Some studies found that laser irradiation may either enhance, inhibit, or has no effect on the function of a variety of microorganisms and cells. Animal studies also offered some basis for treatment. Improvements, particularly in the earliest phases of wound healing, have been reported following laser irradiation. METHODS: We used Argon Laser (488-514 nm) and Krypton Laser (670 nm) in the study. The laser beam was delivered through a system of fiber optic in Argon Laser and reflector in Krypton Laser. The rats treated were restrained in a Plexiglas cage without anesthesia during the laser irradiation period. The percentage of the wound healing acceleration in days and size, actual doses, and estimated clinical doses were calculated as follows: AccD = (1-TD/CD) x 100%, AccS = (1-TA/CA) x 100%, AD = D(in) - D(gl) - D(SR) and ECD = AD = D(sr), respectively. RESULTS: The acceleration effects of wound healing in days (AccD) were 22.93% and 14.54%, size reductions (AccS) were 41.93% and 30.41% at the optimal stimulative incident dose of 20 J/cm2. Zero bioactivation shown at the incident doses of 80 J/cm2 and 100 J/cm2. The inhibitory effects of wound healing in days were -7.72% and -3.37%, in size reduction were -13.35% and -12.88% at the maximal inhibitory incident dose of 140 J/cm2 for Argon and Krypton Lasers, respectively. The actual doses were 5.21 J/cm2 and 4.03 J/cm2, the estimated clinical doses were 5.50 J/cm2 and 4.25 J/cm2 at optimal stimulative incident dose 20 J/cm2 for Argon and Krypton Lasers, respectively. CONCLUSIONS: Low power laser therapy at the appropriate dosimetric parameters can provide the acceleration effects of wound healing on rats. The effects were dependent with the doses and laser wavelengths used. In this experiment, the optimum stimulative dose was 20 J/cm2 and the Argon Laser with 488 nm was more effective than the Krypton Laser with 670 nm. The zero bioactivation and inhibition effect of wound healing on rats occurred in Argon Laser and Krypton Laser.     

Induction of acute phase gene expression by brain irradiation

PURPOSE: To investigate the in vivo acute phase molecular response of the brain to ionizing radiation. METHODS AND MATERIALS: C3Hf/Sed/Kam mice were given midbrain or whole-body irradiation. Cerebral expression of interleukins (IL-1 alpha, IL-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6), interferon (IFN-gamma), tumor necrosis factors (TNF-alpha and TNF-beta), intercellular adhesion molecule-1 (ICAM-1), inducible nitric oxide synthetase (iNOS), von Willebrand factor (vWF), alpha 1-antichymotrypsin (EB22/5.3), and glial fibrillary acidic protein (GFAP) was measured at various times after various radiation doses by ribonuclease (RNase) protection assay. The effects of dexamethasone or pentoxifylline treatment of mice on radiation-induced gene expression were also examined. RESULTS: Levels of TNF-alpha, IL-1 beta, ICAM-1, EB22/5.3 and to a lesser extent IL-1 alpha and GFAP, messenger RNA were increased in the brain after irradiation, whether the dose was delivered to the whole body or only to the midbrain. Responses were radiation dose dependent, but were not found below 7 Gy; the exception being ICAM-1, which was increased by doses as low as 2 Gy. Most responses were rapid, peaking within 4-8 h, but antichymotrypsin and GFAP responses were delayed and still elevated at 24 h, by which time the others had subsided. Pretreatment of mice with dexamethasone or pentoxifylline suppressed radiation-induced gene expression, either partially or completely. Dexamethasone was more inhibitory than pentoxifylline at the doses chosen. CONCLUSIONS: The initial response of the brain to irradiation involves expression of inflammatory gene products, which are probably responsible for clinically observed early symptoms of brain radiotherapy. This mechanism explains the beneficial effects of the clinical use of steroids in such circumstances.     

Three-dimensional visualization and measurement of conformal dose distributions using magnetic resonance imaging of BANG polymer gel dosimeters

PURPOSE/OBJECTIVE: The measurement of complex dose distributions (those created by irradiation through multiple beams, multiple sources, or multiple source dwell positions) requires a dosimeter that can integrate the dose during a complete treatment. Integrating dosimeter devices generally are capable of measuring only dose at a point (ion chamber, diode, TLD) or in a plane (film). With increasing use of conformal dose distributions requiring shaped, noncoplanar beams, there will be an increased requirement for a dosimeter that can record and display a 3D dose distribution. The use of a 3D dosimeter will be required to confirm the accuracy of treatment plans produced by the current generation of 3D treatment-planning computers. METHODS AND MATERIALS: The use of a Fricke-infused gel and magnetic resonance imaging (MRI) to demonstrate the localization of stereotactic beams has been demonstrated (11). The recently developed BANG polymer gel dosimetry system (MGS Research, Inc., Guilford, CT), based on radiation-induced chain polymerization of acrylic monomers dispersed in a tissue-equivalent gel, surpasses the Fricke-gel method by providing accurate, quantitative dose distribution data that do not deteriorate with time (6, 9). The improved BANG2 formulation contains 3% N,N'-methylene-bisacrylamide, 3% acrylic acid, 1% sodium hydroxide, 5% gelatin, and 88% water, where all percentages are by weight. The gel was poured into volumetric flasks, of dimensions comparable to a human head. The gels were irradiated with complex beam arrangements, similar to those used for conformal radiation therapy. Images of the gels were acquired using a Siemens 1.5T imager and a Hahn spin-echo pulse sequence (90 degrees-tau-180 degrees-tau-acquire, for different values of tau). The images were transferred via network to a Macintosh computer for which a data analysis and display program was written. The program calculates R2 maps on the basis of multiple TE images, using a monoexponential nonlinear least-squares fit based on the Levenberg-Marquardt algorithm. The program also creates a dose-to-R2 calibration function by fitting a polynomial to a set of dose and R2 data points, obtained from gels irradiated in test tubes to known doses. This function can then be applied to any other R2 map, so that a dose map can be computed and displayed. RESULTS: Through exposure to known doses of radiation, the gel has been shown to respond linearly with dose in the range of 0 to 10 Gy, and its response is independent of the beam energy or modality. Dose distributions have been imaged in orthogonal planes, and can be displayed in a convenient form for comparison with isodose plans. The response of the gel is stable; the gel can be irradiated at any time after its manufacture, and imaging can be conducted any time following a brief interval after irradiation. CONCLUSION: The polymer gel dosimeter has been shown to be a valuable device for displaying three-dimensional dose distributions. The imaged dose distribution can be compared easily with calculated dose distributions, to validate a treatment planning system. In the future, gels may be prepared in anthropomorphic phantoms, to confirm unique patient dose distributions.     

Inhibition and activation of the thyroidal axis by the adrenal axis in vertebrates

PURPOSE: To determine the long-term effects of 75.6- and 81.0-Gy doses of three-dimensional conformal radiation therapy in a dose-escalation study in patients with stage T2c-T3 prostatic cancer. MATERIALS AND METHODS: Fifty patients received an initial 75.6-Gy dose, and the dose in 46 patients was subsequently escalated to 81.0-Gy. Median follow-up was 60 and 40 months, respectively. RESULTS: The rates of effects of acute toxicity during the course of treatment were similar for both dose levels. Among the 96 patients, the rate of grade 2 morbidities necessitating medication to relieve acute symptoms was 17% (16 patients) for rectal and 36% (35 patients) for urinary morbidities. All other patients had either no or grade 1 morbidities. Fourteen patients (15%) developed late grade 2 rectal morbidities. There were no differences in 5-year actuarial rates of late grade 2 rectal or urinary morbidities among patients who received 75.6 Gy versus those who received 81.0 Gy. One patient treated with 81.0 Gy developed a grade 3 urethral stricture, which was resolved with dilatation. CONCLUSION: Tumor dose escalation beyond conventional radiation doses for localized prostatic cancer is feasible when delivered with three-dimensional conformal radiation therapy, with no increase in morbidity in normal tissue.     

Cigarette smoking and treatment outcomes in Graves ophthalmopathy

BACKGROUND: It is unclear whether smoking affects the course of Graves ophthalmopathy and therapeutic outcomes. OBJECTIVE: To observe smoking behavior in a randomized study of the effect of radioiodine therapy on ophthalmopathy and in a case series of patients with Graves ophthalmopathy receiving orbital radiation therapy and glucocorticoids. DESIGN: Randomized, single-blind study of smoking and mild ophthalmopathy after radioiodine therapy (study 1) and a retrospective cohort study of the association between smoking and response of severe ophthalmopathy to treatment (study 2). SETTING: University medical center. PATIENTS: 300 patients with mild ophthalmopathy (study 1) and 150 patients with severe ophthalmopathy (study 2). INTERVENTION: In study 1, patients received radioiodine alone or radioiodine and a 3-month course of oral prednisone (initial dosage, 0.4 to 0.5 mg/kg of body weight per day). In study 2, patients received high-dose oral prednisone for 6 months (initial dosage, 80 to 100 mg/d) and underwent orbital radiation therapy by linear accelerator (cumulative dose, 20 Gy per eye over 2 weeks). MEASUREMENTS: Degree of ophthalmopathy was assessed by overall evaluation (inflammatory changes, proptosis, extraocular muscle dysfunction, corneal involvement, and optic neuropathy). RESULTS: In study 1, ophthalmopathy progressed in 4 of 68 nonsmokers (5.9% [95% CI, 3% to 9%]) and 19 of 82 smokers (23.2% [CI, 13% to 33%]) who received radioiodine alone (P = 0.007). Ophthalmopathy was alleviated in 37 of 58 nonsmokers (63.8% [CI, 51% to 78%]) and 13 of 87 smokers (14.9% [CI, 10% to 26%]) who received radioiodine plus prednisone (P < 0.001). In study 2, 61 of 65 nonsmokers (93.8% [CI, 90% to 98%]) and 58 of 85 smokers (68.2% [CI, 57% to 78%]) responded to treatment (P < 0.001). CONCLUSIONS: Cigarette smoking increases the risk for progression of ophthalmopathy after radioiodine therapy and decreases the efficacy of orbital radiation therapy and glucocorticoid therapy.     

Cost benefit of emerging technology in localized carcinoma of the prostate

PURPOSE: In a health care environment strongly concerned with cost containment, cost-benefit studies of new technology must include analyses of loco-regional tumor control, morbidity, impact on quality of life, and financial considerations. METHODS AND MATERIALS: This nonrandomized study analyzes 124 patients treated with three-dimensional conformal radiation therapy (3D CRT) and 153 with standard irradiation (SRT) between January 1992 and December 1995, for histologically proven adenocarcinoma of prostate, clinical Stage T1 or T2. Mean follow-up is 1.4 years. Three-dimensional CRT consisted of six or seven coplanar oblique and lateral and, in some patients, AP fields designed to treat the prostate with a 1 to 1.7 cm margin. SRT consisted of 120 degrees bilateral arc rotation. Total doses to prostate were 67 to 70 Gy when pelvic lymph nodes were irradiated or 68.4 to 73.8 Gy when prostatic volume only was treated; dose per fraction was 1.8 Gy. Patients were interviewed weekly for severity of 12 acute intestinal and urinary pelvic irradiation side effects (0 to 4+ grading). Time and effort for 3D RTP and daily treatment with 3D CRT and SRT were recorded. Dose-volume histograms (DVHs) were calculated for gross tumor volume, planning target volume, bladder, and rectum. Actual reimbursement to the hospital and university was determined for 41 3D CRT, 43 SRT, and 40 radical prostatectomy patients treated during the same period. RESULTS: Average treatment planning times (in minutes) were: 101 for 3D conformal therapy simulation, 66 for contouring of target volume and sensitive structures, 55 for virtual simulation, 39 for plan preparation and documentation, 65 for physical simulation, and 20 for approval of treatment plan. Daily mean treatment times were 19 min for 3D CRT with Cerrobend blocking, 16 with multileaf collimation, and 10 with bilateral arc rotation. Dosimetric analysis (DVHs) showed a reduction of 50% in volume of bladder or rectum receiving doses higher than 65 Gy. Acute side effects included dysuria, moderate difficulty in urinating, and nocturia in 25-39% of both SRT and CRT patients; loose stools or diarrhea in 5-12% of 3D CRT and 16-22% of SRT patients; moderate proctitis in 3% of 3D CRT and 12% of SRT patients (p = 0.01). Chemical disease-free survival (prostate-specific antigen < or =2 ng/ml) at 3 years was 90% with 3D CRT and 80% with SRT (p = 0.01). Average initial treatment reimbursements were $13,823 (3D CRT), $10,864 (SRT), and $12,250 (radical prostatectomy). Average total treatment reimbursement and projected cost of management of initial therapy failures per patients were $15,173, $16,264, and $16,405, respectively. CONCLUSIONS: Three-dimensional CRT irradiated less bladder and rectum volume than SRT; CRT initial reimbursement was 28% higher than SRT and 12% higher than radical prostatectomy. Because of projected better local tumor control, average total cost of treating a patient with 3D CRT or radical prostatectomy is equivalent to cost of SRT. Treatment morbidity was lower with 3D CRT. Our findings reflect an overall benefit with 3D CRT as a new promising technology in treatment of localized prostate cancer. Dose-escalation studies may enhance its efficacy and cost benefit.     

Treatment of intrahepatic cancers with radiation doses based on a normal tissue complication probability model

PURPOSE: To attempt to safely escalate the dose of radiation for patients with intrahepatic cancer, we designed a protocol in which each patient received the maximum possible dose while being subjected to a 10% risk of radiation-induced liver disease (RILD, or radiation hepatitis) based on a normal tissue complication probability (NTCP) model. We had two hypotheses: H1; with this approach, we could safely deliver higher doses of radiation than we would have prescribed based on our previous protocol, and H2; the model would predict the observed complication probability (10%). PATIENTS AND METHODS: Patients with either primary hepatobiliary cancer or colorectal cancer metastatic to the liver and normal liver function were eligible. We used an NTCP model with parameters calculated from our previous patient data to prescribe a dose that subjected each patient to a 10% complication risk within the model. Treatment was delivered with concurrent hepatic arterial fluorodeoxyuridine (HA FUdR). Patients were evaluated for RILD 2 and 4 months after the completion of treatment. RESULTS: Twenty-one patients completed treatment and were followed up for at least 3 months. The mean dose delivered by the current protocol was 56.6 +/- 2.31 Gy (range, 40.5 to 81 Gy). This dose was significantly greater than the dose that would have been prescribed by the previous protocol (46.0 +/- 1.65 Gy; range, 33 to 66 Gy; P < .01). These data are consistent with H1. One of 21 patients developed RILD. The complication rate of 4.8% (95% confidence interval, 0% to 23.8%) did not differ significantly from the predicted 8.8% NTCP (based on dose delivered) and excluded a 25% true incidence rate (P < .05). This finding supports H2. CONCLUSION: Our results suggest that an NTCP model can be used prospectively to safely deliver far greater doses of radiation for patients with intrahepatic cancer than with previous approaches. Although the observed complication probability is within the confidence intervals of our model, it is possible that this model overestimates the risk of complication and that further dose escalation will be possible. Additional follow-up and accrual will be required to determine if these higher doses produce further improvements in response and survival.     

Comparative dynamics of elimination of potential chromosome damage in mouse bone marrow cells after low and moderate doses of radiation

Possible dynamics of the incidence, repair, and realization of potential chromosome aberrations (PAs) was examined by indirect methods based on cytogenetic analysis of radiation effects. PAs were characterized as chemical modifications of DNA responsible for the incidence of structural aberrations of chromosomes. We interpreted our data as providing evidence that two types of radiation-induced PAs, differing in repair rates, could occur in the exposed cells: quick- (short-term) and slow (long-term) repairing PAs. We showed that the PA spectrum gradually changed with an increase in radiation dose within the interval from 24 to 150 cGy. This process was paralleled by changes in the cell response and chromosome resistance to radiation. Short-term PAs were induced mainly by low radiation doses ranging from 24 to 75 cGy. Their incidence was associated with activation of the corresponding repair process. Further increase in radiation dose resulted in changes in the PA spectrum, and doses of 150 cGy induced predominantly long-term PAs with concomitant activation of the appropriate repair process. Induction of repair occurred in the dose intervals limited by lower and upper threshold doses, Dl and Du. In our experiments, short-term PAs were repaired when Dl < 24 cGy and 126 cGy < Du < < 150 cGy. Long-term PAs were repaired when 75 cGy < Dl < 99 cGy and Du > 150 cGy.     

Ventricular tachycardia--diagnosis and therapy

We report a case of radiation-induced optic neuropathy in a 32-year-old man with Cushing's disease and a recurrent tumour of the left cavernous sinus. The patient experienced rapid, painless loss of vision 4 years after treatment without recurrence of tumour or other visual disorder. MRI showed enlargement and contrast enhancement of the optic chiasm. A year later the patient was almost blind and MRI showed atrophy and persistent contrast enhancement of the chiasm.     

Graves' ophthalmopathy

Ophthalmopathy develops in about 30% of patients who have Graves' disease. The pathogenesis, like that of the hyperthyroidism, is probably autoimmune in nature. The eye manifestations are diverse and include lid lag, soft tissue swelling, proptosis, corneal damage, diplopia, and optic neuropathy. The natural history is benign in 90% of patients, with gradual improvement over time. Therapeutic options include corticosteroid therapy, radiation, and surgical treatment. The last is usually the therapy of choice for severe or disfiguring ophthalmopathy.     

Simplified method for three-dimensional evaluation of interstitial brachytherapy applications

Although three-dimensional (3-D) treatment planning has primarily been used for external beam radiation therapy, the advantages of 3-D treatment planning can be realized for brachytherapy applications. As with teletherapy, the use of 3-D treatment planning for brachytherapy can provide both superior dose distribution as well as detailed evaluations of the relationship of dose and volume in critical structures and target tissues. Conventional 3-D treatment planning uses computed tomography (CT) scans to localize structures; however, localizing individual brachytherapy sources on each CT slice can be impractical for routine clinical use. In the transition from two-dimensional to 3-D localization and dose evaluation of interstitial perineal templates in particular, a practical method of seed localization on a postimplant CT dataset has been developed. This method does not utilize dummy sources and, as such, does not require individual seed locations to be identified. Instead, the position of the afterloading catheter is defined as a reference line by connecting its location as seen on the axial CT slices and seed locations defined along its length. Full volumetric calculations can then be performed, including dose-volume histograms (DVH) for critical organs and tumor volumes. Source localization and normal tissue doses were calculated using both orthogonal films and the 3-D method for a series of perineal template guided implants. Point dose calculations of the rectum and bladder were obtained from orthogonal films and were then compared to the corresponding DVHs for these organs.     

Pharmacokinetic monitoring and dose modification of etanidazole in the RTOG 85-27 phase III head and neck trial

PURPOSE: To prospectively evaluate the pharmacokinetic monitoring and drug dose adjustment of Etanidazole (Eta) in patients treated on the RTOG randomized trial for Stage III and IV head and neck cancer. METHODS AND MATERIALS: From June, 1986 to October, 1991, 521 patients were randomized to conventional RT alone or RT plus Eta. The primary goal was to determine whether the addition of Eta to conventional radiation therapy improves local-regional control and tumor-free survival. Of the 264 patients who received Eta, 233 had their drug exposure calculated and the Eta dose and schedule adjusted accordingly to prevent the occurrence of serious peripheral neuropathy. Drug exposure was assessed using the area under the curve (AUC) for a single treatment that was calculated by the integral over time of the serum concentration of Eta. The total drug exposure (total-AUC) was estimated by multiplying the AUC by the number of drug administrations. RESULTS: Eighteen percent of patients developed Grade I and 6% developed Grade II peripheral neuropathy. There was no Grade 3 or 4 peripheral neuropathy. There is a trend for an increased risk of neuropathy by single dose AUC. The minimal difference in incidence of neuropathy by single-dose AUC was due to the use of dose and schedule modification for patients with the higher values. CONCLUSIONS: The pharmacokinetics investigated in this study confirm previous work that monitoring Eta levels, with dose adjustment, allows it to be used safely in the clinic. In a subset analysis there was a statistically significant improvement in local-regional control and survival rates for patients with N0 and N1 disease, that will require confirmation (14). However, the clinical efficacy of Eta in this trial proved to be of little overall benefit.