Development of a 3-D visible limiter imaging system for the HSX stellarator.

A visible camera diagnostic has been developed to study the Helically Symmetric eXperiment (HSX) limiter plasma interaction. A straight line view from the camera location to the limiter was not possible due to the complex 3D stellarator geometry of HSX, so it was necessary to insert a mirror/lens system into the plasma edge. A custom support structure for this optical system tailored to the HSX geometry was designed and installed. This system holds the optics tube assembly at the required angle for the desired view to both minimize system stress and facilitate robust and repeatable camera positioning. The camera system has been absolutely calibrated and using Hα and C-III filters can provide hydrogen and carbon photon fluxes, which through an S/XB coefficient can be converted into particle fluxes. The resulting measurements have been used to obtain the characteristic penetration length of hydrogen and C-III species. The hydrogen λiz value shows reasonable agreement with the value predicted by a 1D penetration length calculation.

The course of seizure disorders in patients with malignant gliomas.

OBJECTIVE: To describe the morbidity associated with seizures and the efficacy of anticonvulsant therapy in adult patients with malignant gliomas (MGs). STUDY DESIGN: A retrospective review of charts was performed to determine the occurrence of seizures at diagnosis, the frequency and character of subsequent seizures, and the use and toxic side effects of anticonvulsants. PATIENTS: Sixty-five consecutive adult patients with supratentorial MGs who were examined in the neurooncology clinic at a university medical center were studied. The diagnosis was glioblastoma in 47 of the patients, and it was anaplastic astrocytoma in 18 patients. The mean age of the patients was 49.5 years. The median Karnofsky status score was 80. The median survival was 18 months. RESULTS: Twenty-nine patients presented with seizures, and 21 of these had subsequent (eg, "recurrent") seizures while they were receiving anticonvulsant therapy. Ten of 36 patients who were free of seizures at diagnosis experienced seizures after diagnosis (eg, "late onset") while they were being treated with anticonvulsants, including five patients who had single seizures. Long-term seizure frequency in excess of one per month was observed in 13 patients. Ten patients had episodes of partial motor status epilepticus. Most recurrent and late-onset seizures occurred despite therapeutic anticonvulsant levels, and without evidence of tumor progression. Rash associated with anticonvulsants was observed in 26% of the patients. Other clinically important toxic side effects were observed in 14% of the patients who were receiving long-term anticonvulsant therapy. CONCLUSIONS: Seizures contributed substantially to the neurologic morbidity of MGs in at least 25% of these patients. The occurrence of seizures at diagnosis was a strong predictor of subsequent seizures, and in many patients, seizures proved to be refractory to standard anticonvulsant therapy. Long-term anticonvulsant toxic side effects are relatively common in patients with MGs. The use of long-term seizure prophylaxis for patients with MGs who are free of seizures at presentation is not clearly beneficial and should be studied in a prospective trial.

Synthesis of heat shock proteins following oxidative challenge: role of glutathione.

The relationship between glutathione metabolism, menadione sodium bisulphite oxidation of protein thiols, and the synthesis of hsc70 was investigated using CHO cells. A 30-min/37 degrees C exposure to menadione, a compound which redox cycles to produce superoxide anion radicals and hydrogen peroxide, resulted in rapid accumulation of hsc70 mRNA. PAGE and Western blot analysis indicated increased synthesis such that accumulation of hsc70 occurred. These changes were preceded by rapid oxidation of GSH to GSSG, followed by GSH depletion, and subsequent protein thiol oxidation. As a test of whether a correlation existed between GSH oxidation and depletion, protein thiol oxidation and hsp synthesis, cells were exposed to menadione in the absence and presence of glucose. Synthesis of hsc70 was increased in cells exposed to menadione in the absence of glucose compared with its presence. As a further test, cells were exposed to BSO/DEM in order to deplete GSH and then exposed to menadione. The synthesis of hsc70 following exposure to menadione was greatly increased in GSH-depleted cells compared with GSH-replete cells. Experiments were conducted to determine if electroporation of cells in GSSG containing buffer affected hsp synthesis. Electroporation in glucose-free buffer containing 3 mM GSSG did not affect hsp synthesis. We interpret these results to indicate that the inability to maintain glutathione in a reduced form during menadione redox cycling resulted in protein thiol oxidation. This, in turn, resulted in accumulation of hsc70 mRNA with a subsequent increase in the synthesis of hsc70.

Current radiosurgery practice: results of an ASTRO survey. Task Force on Stereotactic Radiosurgery, American Society for Therapeutic Radiology and Oncology.

PURPOSE: Although there is increasing interest in radiosurgery, little quantitative data regarding current patterns of radiosurgery practice are available. We developed a radiosurgery questionnaire to obtain information on radiosurgery practice. METHODS AND MATERIALS: We distributed the questionnaire to the entire membership of the American Society of Therapeutic Radiology and Oncology in early 1993. Responses were obtained from 74 facilities that practice radiosurgery, corresponding to over 6000 treatments carried out since 1983 by 135 radiation oncologists and 130 physicists. RESULTS: Most respondents were found to work within a multidisciplinary team, consisting of the following specialists (average hours devoted per patient on day of treatment in parentheses): radiation oncologist (3.8), neurosurgeon (3.2), physicist (6.1), radiologist (0.7), nurse (2.7), other (3.0). On average, neurosurgeons and nurses who perform Gamma Knife radiosurgery devote significantly more time-per-patient on the day of treatment than their peers who perform linac radiosurgery. On average, less experienced radiation oncologists and physicists (< or = 24 months experience, or < or = 50 patients treated) devote significantly more time-per-patient on the day of treatment than their more experienced peers. Although there are many more linac radiosurgery facilities than Gamma Knife facilities, on average the number of patients treated per month per facility is significantly larger at the latter. On average, follow-up responsibilities are nearly equally shared by radiation oncologists and neurosurgeons, except at Gamma Knife facilities, where neurosurgeons assume a larger percentage of follow-up responsibility. The percentages of patients treated at linac facilities for metastases or primary CNS malignancy are larger than the corresponding percentages at Gamma Knife facilities; the opposite is true for arteriovenous malformation, acoustic neuroma, and meningioma. CONCLUSION: Current radiosurgery practice usually involves a team approach, with participation of specialists from radiation oncology, neurosurgery, physics, radiology, and nursing. The average number of M.D. and Ph.D. hours required per treatment on the day of radiosurgery is high.

Synthesis of hsp-70 is enhanced in glutathione-depleted Hep G2 cells.

The question of whether depletion of glutathione (GSH) could affect the synthesis of stress proteins was investigated in Hep G2 cells. Cells were exposed to BSO/DEM at 37 degrees C to deplete glutathione. When 95% of the glutathione was depleted cells were washed, and BSO was added to cells previously exposed to BSO/DEM; then the cells were incubated at 37, 38.5, or 39 degrees C for 4 h. Two-dimensional PAGE analysis of GSH-depleted cells incubated at 37 degrees C indicated increased synthesis of heme oxygenase and a polypeptide tentatively identified as hsp-70B'. Depletion of GSH did not affect the cellular concentration of hsp-70 as assessed by Western immunoblotting, yet Northern blot analysis indicated that hsp-70 mRNA was increased in GSH-depleted cells. Incubation of GSH-replete cells at 38.5 degrees C did not appear to enhance the amount of hsp-70 mRNA or the relative rate of hsp-70 synthesis. In contrast, incubation of GSH-depleted cells at 38.5 degrees C elevated steady-state hsp-70 mRNA levels and the rate of hsp-70 synthesis relative to total protein synthesis. Depletion of GSH also increased the relative rate of hsp-70 synthesis at 39 degrees C. These results suggest that the synthesis of stress proteins can be affected by glutathione concentrations.

Depletion of glutathione after gamma irradiation modifies survival.

The relationship between the intracellular glutathione (GSH) concentration and the aerobic radiation response was studied in Chinese hamster ovary cells. Various degrees of GSH depletion were produced by exposure to buthionine sulfoximine (BSO) and/or diethyl maleate (DEM). Diethyl maleate did not act as a classical radiosensitizer under the experimental conditions employed, nor did exposure to DEM/BSO nonspecifically affect protein thiols as measured by thiol blotting. Dose-response curves were obtained using cells irradiated in the absence or presence of DEM/BSO, which decreased GSH levels by 90-95%. Exposure to DEM/BSO did not affect the formation of DNA single-strand breaks or DNA-protein crosslinks measured immediately after irradiation performed at ice temperatures. Analysis of survival curves indicated that the Dq was decreased by 18% when GSH depletion occurred prior to, during, and after irradiation. The DEM/BSO exposure did not affect D0. To study postirradiation conditions, cells were exposed to 10 microM DEM prior to and during irradiation, which was performed at ice temperatures. Levels of GSH were depleted by 75% by this protocol. Immediately after irradiation, the cells were rapidly warmed by the addition of 37 degrees C growth medium containing either 10 or 90 microM DEM. Addition of 10 microM DEM after irradiation did not affect the degree of depletion, which remained constant at 75%. In contrast, GSH depletion was increased to 90% 10 min after addition of the 90 microM DEM. Addition of 90 microM DEM after irradiation produced a statistically significant difference in survival compared to addition of 10 microM DEM. In a second depletion protocol, cells were exposed to 100 microM DEM at room temperature for 5 min, irradiated, incubated at 37 degrees C for 1 h, washed, and then incubated in 50 microM BSO for 24 h. This depletion protocol reduced survival by a factor of 2.6 compared to cells not exposed to the combination of DEM/BSO. Survival was not affected if the cells were exposed to the DEM or BSO alone. This was interpreted to indicate that survival was not affected by GSH depletion occurring after irradiation unless depletion was rapid and sustained. The rate of repair of sublethal and potentially lethal damage was measured and found to be independent of the DEM/BSO exposure. These experimental results in addition to previous ones (Freeman and Meredith, Int. J. Radiat. Oncol. Biol. Phys. 13, 1371-1375, 1987) were interpreted to indicate that under aerobic conditions GSH depletion may alter the expression of radiation damage by affecting metabolic fixation.

Questionnaires in behavioral pediatrics: guidelines for selection and use.

There is a death of information for pediatricians to use in choosing questionnaires that would be useful in medical practice. In this article, general guidelines are presented for primary child health clinicians to use in selecting questionnaires. Concepts such as reliability, validity, readability, response format, scoring and completion time, and norms are reviewed, and the implications of these concepts for practitioners are discussed. Guidelines are applied to selected behavioral questionnaires to illustrate their importance.

Obtaining parental perceptions of the quality of services for children with special health needs.

Analyzed responses from 295 parents across two service delivery sites to identify specific factors of satisfaction. Although General Satisfaction accounted for most variance, Clarity of Communication, Preappointment Wait and Information, and Clinic Efficiency were also identified as factors. Results are discussed in the context of a collaborative relationship between parents and providers. A shortened questionnaire that efficiently taps these areas of satisfaction is appended.

Failure of chronic glutathione elevation to reduce cytotoxicity produced by exposure to cis-diamminedichloroplatinum(II), ionizing radiation, or hyperthermia.

Chinese hamster ovary (CHO) cells cultured in vitro were continuously exposed to increasing concentrations of diethylmaleate (DEM). Chronic exposure of these cells (designated CHO/DEM) to 80 microM diethylmaleate resulted in an increase in cystine transport, a decrease in glutathione inhibition of the enzyme gamma-glutamylcysteine synthetase, elevation of intracellular glutathione levels to 4.3 times control, and elevation of glutathione-S-transferase activity by 6.6 times. Yet, CHO/DEM and control CHO cells exhibited the same ability to synthesize protein as measured by two-dimensional electrophoresis, the same cell cycle distribution, and the same population doubling times. CHO/DEM cells are resistant to DEM and diamide cytotoxicity, compared to control CHO cells. CHO/DEM cells were used to address the question of whether chronic elevation of glutathione, above control concentrations, reduced the cytotoxicity produced by exposure to cisplatin, gamma-radiation, or hyperthermia. The resulting dose-response curves obtained with CHO/DEM and control CHO cells indicated that chronic exposure to DEM, which resulted in chronic elevation of glutathione, did not provide protection against any of the three toxic treatments.

Primary malignant extragonadal germ cell tumors. An analysis of the effect of the effect of radiotherapy.

A retrospective analysis was performed on all patients diagnosed with biopsy-proven extragonadal germ cell tumors at the University of Virginia (Charlottesville, VA), The Medical University of South Carolina (Charleston, SC), the Bethesda Naval Hospital (Bethesda, MD), and The Medical College of Virginia (Richmond, VA) for the time period of January 1965 to December 1984. A total of 54 patients were treated with the initial sites of presentation observed: mediastinum, 26; central nervous system, 14; retroperitoneum, eight; and sacrococcygeal region, six. Megavoltage irradiation was used in 44 patients with a dose range of 2400 to 5580 cGy (mean, 4213 cGy). With a minimum follow-up of 4.0 years and a mean follow-up of 10.8 years, the 5-year actuarial survival for the entire population was 57.8%. Local control was achieved in 26 of 44 (59%) of the irradiated population. Factors of prognostic significance included histologic type at presentation, site of presentation, and radiation doses greater than or equal to 4000 cGy. Radiotherapy appears to be an effective modality in patients with extragonadal seminomas; however, the nonseminomatous tumors do not appear to be as radioresponsive.

Total lymphoid irradiation in heart transplantation: adjunctive treatment for recurrent rejection.

In the face of recurrent heart transplant graft rejection refractory to all conventional immunotherapy, retransplantation is customary treatment. The case of a heart transplant recipient unsuitable for retransplantation whose recurrent rejection was successfully treated with postoperative total lymphoid irradiation is described.

Facilitating play in hospitalized handicapped children: the design of a therapeutic play environment.

The development of a play environment is described, including a play structure that was designed to facilitate symbolic play in hospitalized, handicapped children. The effect of the structure on play was tested on handicapped children aged 2 to 13 years who were verbal and able to use at least one hand. Twenty-five pretest and 25 posttest observations were conducted and data were coded into play and nonplay categories. Results indicated decline in aimless wandering and nonplay activities, with a concomitant increase in both partial and symbolic play. The implications for play among hospitalized, handicapped children are discussed.

Postoperative radiation as adjuvant treatment for carcinoma of the oral cavity, larynx, and pharynx: preliminary report of a prospective randomized trial.

A prospective randomized trial was performed in patients with advanced squamous cell carcinomas (SCC) of the oral cavity, larynx, and pharynx to examine the effect of adjuvant postoperative radiation therapy on locoregional recurrence and survival following "curative" resection. Fifty-one patients with stage III or IV SCC treated from 1981 through 1984 were randomized to receive either surgery alone (n = 27) or surgery with postoperative radiation (n = 24). Five patients were excluded from the study after randomization because of ineligibility or protocol violations. Overall recurrence rates of 55.6% and 36.8% were noted in the surgery and surgery with adjuvant radiotherapy arms, respectively (p = NS). This trend towards a higher recurrence rate in the surgery only arm was in part due to the development of lymph node metastases in the contralateral, nonoperated neck. Thus far, no significant differences in either locoregional or overall survival have been noted between the two treatment arms. In this preliminary analysis, adjuvant postoperative radiotherapy does not appear to improve disease-free or overall survival.

Primary central nervous system germ cell tumors. Effect of histologic confirmation on radiotherapy.

Primary malignant intracranial germ cell tumors are rare lesions responsible for only 0.5% of all central nervous system (CNS) malignancy. With stereotactic localization these lesions can be safely biopsied, and histologic confirmation will affect the ultimate prognosis. This report is a multi-institutional retrospective analysis of 33 patients diagnosed with a primary CNS germ cell tumor. Tumors in 14 patients (42%) were histologically confirmed (13 germinoma and one embryonal cell carcinoma); 19 patients were treated with a presumptive diagnosis. All patients were irradiated with a dose range of 3950 cGy to 6000 cGy to the primary lesions. Eight patients received craniospinal irradiation, and 25 patients were locally treated. The 5-year actuarial survival for the entire population was 64%. The survival rate in patients with histologic confirmation was 79% versus 53% in the unbiopsied population. Radiation doses greater than 5000 cGy, radiotherapy volume, and age were prognostic factors in determining survival.

1986 Association of Residents in Radiation Oncology Survey.

Two simultaneous surveys were conducted by the Association of Residents in Radiation Oncology (ARRO). A survey of all residents in Radiation Oncology was conducted to obtain information on trends in residency training. A simultaneous survey of Chief Residents was obtained to determine more specific information on current training programs. Over one-half of residents responded. Eighty-eight percent of respondents were graduates of a North American medical school. Most did at least an internship prior to entering Radiation Oncology and 3/4 of those who did not do a separate internship rotated through other areas at a later time to broaden their knowledge. One-half are Board certified or Board eligible in another specialty or hold a Masters or Ph.D. degree. Three-quarters of all residents had authorship of at least one paper during training and one-half were primary authors. Eighty percent felt adequately prepared for practice after residency. One-half plan at least an initial post-residency affiliation with an academic center. Many were concerned that Radiation Oncologists are not afforded respect equivalent to that of other specialties. Ninety-eight percent favored departmental status for Radiation Oncology. Resident recommendations for improving the image of Radiation Oncology are presented.