Biomedical subjects

S L Brown

Publications and source records attributed to S L Brown.

At least 37 records · Page 2Linked to original sources

PubMed2001

Integrin alpha(v)beta1 is an adenovirus coreceptor.

The human embryonic kidney (HEK293) cell line, commonly used for recombinant adenovirus (Ad) propagation, does not express the Ad coreceptor alpha(v)beta3 or alpha(v)beta5 integrins, yet these cells are efficiently infected by Ad vectors. Here we demonstrate that Ad binds to HEK293 cells via the fiber receptor CAR and is subsequently internalized via interaction with integrin alpha(v)beta1. Function-blocking antibodies directed against alpha(v) or beta1, but not beta3, beta5, or alpha5, integrin subunits block Ad infection and viral endocytosis. Therefore, alpha(v)beta1 serves as a coreceptor for Ad infection, and the lack of beta3 and/or beta5 but the relatively high expression of alpha(v)beta1 integrins on certain tumor cell types may explain why these cells are readily transduced by Ad vectors.

Adenoviridae↗

PubMed2001

Variations in utilization and cost of inpatient psychiatric services among adults in Maryland.

The author examined variations in the clinical characteristics, costs, utilization, and discharge patterns of adult inpatients who were hospitalized for psychiatric disorders in Maryland state general hospitals in 1998. Administrative discharge data on all 30,121 adult psychiatric patients in the state in 1998 were used to calculate descriptive statistics on elderly (age 65 years and over) and nonelderly (age 19 to 64 years) patients. The most common reasons for hospitalization were substance-related disorders, which affected 25 percent of the patients, and major depressive disorders, which affected 24.6 percent of the patients. After the effects of Medicare's prospective payment system were disregarded, the average cost of treating elderly persons for depression was calculated to be around 80 percent higher than national estimates.

Adult↗

PubMed2001

Laparoscopic live donor nephrectomy: a comparison with the conventional open approach.

PURPOSE: Laparoscopic live donor nephrectomy is an emerging technique that has not yet gained widespread acceptance in the transplant community due to perceived technical difficulties. However, the potential advantages of decreasing donor morbidity, decreasing hospital stay and improving convalescence while producing a functional kidney for the recipient may prove to enhance living related renal transplantation. We report our early experience with laparoscopic live donor nephrectomy. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 50 consecutive laparoscopic nephrectomies performed from October 1998 to May 2000 and compared them with 50 consecutive open donor nephrectomies, which served as historical controls. RESULTS: Donor age, donor sex and number of HLA mismatches did not differ statistically in the 2 groups. In the laparoscopic and open nephrectomy groups mean followup was 109 and 331 days (p = 0.0001), mean operative time was 234 and 208 minutes (p = 0.0068), mean estimated blood loss was 114 and 193 ml (p = 0.0001), and mean hospital stay was 3.5 and 4.7 days (p = 0.0001), respectively. Average renal warm ischemia time was 2.8 minutes in the laparoscopic nephrectomy group. Serum creatinine did not differ statistically in the 2 groups preoperatively or postoperatively at days 1 and 5, and 1 month. The rate of recipient ureteral complications in the laparoscopic and open nephrectomy groups was 2% (1 of 50 cases) and 6% (3 of 50), respectively (not significant). CONCLUSIONS: Laparoscopic live donor nephrectomy is an attractive alternative to open donor nephrectomy. Laparoscopic nephrectomy results in less postoperative discomfort, an improved cosmetic result and more rapid recovery for the donor with equivalent functional results and complications.

Adult↗

PubMed2001

Silicone gel breast implant rupture, extracapsular silicone, and health status in a population of women.

OBJECTIVE: To assess whether breast implant rupture or extracapsular silicone are associated with selected symptoms of self-reported physician-diagnosed connective tissue disease (CTD). METHODS: Women with silicone gel breast implants responded to a questionnaire that included questions on health status, satisfaction with implants, symptoms of CTD, and physician-diagnosed disease. These women then had magnetic resonance imaging (MRI) of their breasts to determine the status of the implants with respect to rupture and extracapsular silicone. RESULTS: Women with breast implant rupture diagnosed by MRI were no more likely to report a diagnosis of selected CTD than those with intact implants or those with implants of indeterminate status. Women with extracapsular silicone (silicone gel outside of the fibrous scar that forms around breast implants) were more likely to report having fibromyalgia (FM, p = 0.004) or other CTD, which included dermatomyositis, polymyositis, Hashimoto's thyroiditis, mixed CTD, pulmonary fibrosis, eosinophilic fasciitis, and polymyalgia (p = 0.008) than other women in the study. The association with FM remained statistically significant when adjusted for multiple comparisons (7 diagnoses) and implant age, implant location, or implant manufacturer (p < 0.05 in all cases), but became of borderline statistical significance when adjusted for multiple comparisons and self-perceived health status (p = 0.094) or self-perceived rupture status (p = 0.051). The association with other CTD remained statistically significant when adjusted for multiple comparisons and implant location or implant manufacturer, but became borderline or insignificant when adjusted for multiple comparisons and for implant age (p = 0.051), self-perceived health status (p = 0.434), or self-perceived rupture status (p = 0.145). Logistic regression was used to compute odds ratios of self-reported diagnoses comparing women with and without extracapsular silicone. The odds ratios were 2.8 (95% CI 1.2 to 6.3) for FM, and 2.6 (95% CI 0.8 to 8.5) for other CTD after adjustment for implant age, implant location, implant manufacturer, implant type, self-perceived health, self-perceived rupture status, and site of surgery practice. CONCLUSION: These data suggest an association between extracapsular silicone from ruptured silicone breast implants and FM. If this association persists in other studies, women with silicone gel breast implants should be informed of the potential risk of developing fibromyalgia if their breast implants rupture and the silicone gel escapes the fibrous scar capsule.

Adult↗

PubMed2001

Infections related to breast implants reported to the Food and Drug Administration, 1977-1997.

The FDA has a surveillance system for monitoring adverse events related to medical devices. Infection reports submitted to the FDA by breast implant manufacturers between 1977 and 1997 are characterized. Two cases of death caused by toxic shock syndrome after mammoplasty reported to the FDA are presented. Overall, 1,971 reports with a principal adverse event of infection were reported in this time frame. There was a large increase in the number of reports on infections related to breast implants between 1992 and 1995 due to the publicity and litigation surrounding breast implants. When an organism was identified in the report, the most common organism reported was Staphylococcus sp. Information on the time between the implantation and the onset of the infection or the explantation of the implant was not always reported. However, in reports that did contain this information, there were differences between the length of time to infection onset reported for saline breast implants (earlier) compared to silicone gel breast implants (later). More than half of the reports (56.6%) asserted only that there was an infection and that breast implants were explanted as a result; the remaining reports asserted that infection and other signs, symptoms, or diagnoses had afflicted the patient.

Bacterial Infections↗

PubMed2000

Limitations of computed tomography in the preoperative staging of upper tract urothelial carcinoma.

OBJECTIVES: Computed tomography (CT) of the abdomen and pelvis has been used for staging of upper tract urothelial carcinoma. This study was initiated to evaluate the utility of this modality in guiding the management of patients with upper tract urothelial malignancies. METHODS: We performed a retrospective chart review of 37 consecutive patients with urothelial carcinoma of the upper urinary tract (21 renal pelvic, 16 ureteral) who underwent preoperative CT staging of the abdomen and pelvis before open surgical management. RESULTS: CT was not required to establish the diagnosis in any of the patients, but in 16.2% helped to confirm the diagnosis when the disease was suspected based on other studies. CT accurately provided evidence of metastatic disease in only 3% of the patients. CT was accurate in predicting pathologic TNM stage in 59. 5% of patients. The study understaged or did not detect in 16.2% and 24.3%, respectively. Most importantly, CT did not alter the management of any patient. CONCLUSIONS: CT was rarely helpful in establishing the diagnosis of the upper tract urothelial carcinoma and did not influence the management of any patient. We conclude that preoperative CT scan in those patients who are to undergo open surgical management of confirmed urothelial malignancies of the upper urinary tract without suspicion of advanced disease will rarely influence the management of the disease and its use should be selective and not routine.

Carcinoma, Transitional Cell↗

PubMed2000

Association of p130CAS with phosphatidylinositol-3-OH kinase mediates adenovirus cell entry.

The Crk-associated substrate, p130(CAS), has been implicated in the regulation of the actin cytoskeleton following ligation of cell integrins with the extracellular matrix. Integrin-mediated cell adhesion involves p130(CAS) association with focal adhesion kinase (p125(FAK)). Internalization/cell entry of type 2 and type 5 adenoviruses (Ad) is also mediated by alpha(v) integrins. However, expression of dominant negative forms of p125(FAK) does not alter virus entry, and Ad entry occurs normally in p125(FAK)-deficient fibroblasts. We now provide evidence that Ad internalization, a process which is mediated by alpha(v) integrins, also requires p130(CAS) and phosphatidylinositol-3-OH kinase (PI 3-kinase). Ad induces p130(CAS) phosphorylation and inhibition of p130(CAS) phosphorylation by tyrphostin and genistein, or expression of the substrate domain deleted p130(CAS) blocks Ad internalization. p130(CAS) was also found to associate with the p85 subunit of PI 3-kinase through its proline-rich domain during virus internalization and expression of p130(CAS) containing a deleted proline-rich domain (PRD) inhibited adenovirus cell entry. We showed further that the RPLPSPP motif in the proline-rich region of p130(CAS) interacts with the SH3 domain of p85/PI 3-kinase. These studies reveal the molecular basis by which p130(CAS) coordinates the signaling pathways involved in integrin-mediated Ad endocytosis.

Adenoviridae↗

PubMed2000

Venous thrombosis prophylaxis by inflammatory inhibition without anticoagulation therapy.

OBJECTIVE: This study was performed to determine the effectiveness of recombinant P-selectin glycoprotein ligand Ig (rPSGL-Ig) pretreatment to decrease thrombosis and inflammation in experimental venous thrombosis. rPSGL-Ig, a unique mucin-like glycoprotein, has a high affinity for P-selectin. METHODS: Twelve juvenile baboons underwent inferior vena cava (IVC) thrombosis with temporary 6-hour IVC balloon occlusion. Before balloon placement, the animals received rPSGL-Ig (4 mg/kg; n = 8) or saline solution for control (n = 4). The animals underwent evaluation with duplex ultrasound scan imaging, magnetic resonance venography (MRV), phlebography, coagulation profile, and tissue analysis at death for cytokines and vein wall leukocyte morphometrics. With the MRV results, thrombus development, thrombus resolution, and inflammation (gadolinium; square millimeters of enhancement) were assessed. RESULTS: Each animal provided two time points for evaluation (days 2 and 6 after balloon occlusion). A significant decrease in IVC thrombosis between balloons was found in the rPSGL-Ig animals (1 of 16) versus the control animals (5 of 8; P <.01). The MRV results showed significantly less enhancement in the rPSGL-Ig animals at days 2 and 6 (P <.05). Spontaneous thrombus resolution (including balloon sites) was significantly greater from day 2 to day 6 in the rPSGL-Ig animals versus the control animals (23% vs 2%; P <.001), without pulmonary embolism. Lower interleukin-8, platelet factor IV, and monocyte chemotactic protein-1 levels were found in rPSGL-Ig vein walls without significant differences in vein wall leukocyte morphometrics. There were significantly lower D-dimer levels in the rPSGL-Ig-treated animals (P <.05), but there were no differences in measurements of coagulation. Adequate circulating rPSGL-Ig levels were documented. CONCLUSION: Pretreatment with rPSGL-Ig results in: (1) a significant inhibition of thrombosis and vein wall inflammation; (2) a decrease in vein wall cytokine expression; and (3) a promotion of thrombus resolution. Inflammatory inhibition by rPSGL-Ig without anticoagulation therapy provides effective venous thrombosis prophylaxis in experimental venous thrombosis.

Animals↗

PubMed2000

Breast cancer following augmentation mammoplasty (United States).

OBJECTIVE: Although clinical reports have raised concern that breast implants may either increase the risk of breast cancer or delay its diagnosis, epidemiologic studies have generally shown implant recipients to be at a reduced risk of subsequent breast cancer. A large retrospective cohort study was undertaken to clarify effects of cosmetic breast implantation. METHODS: Medical records of 13,488 women receiving cosmetic implants at 18 plastic surgery practices and a group of 3936 patients who received other types of plastic surgery at the same practices were reviewed and information abstracted. Questionnaires were sent to all subjects located as alive, with 71% being completed. Attempts were made to obtain medical verification for all reported cancers and to obtain death certificates for deceased subjects. RESULTS: A total of 136 breast cancers were observed among the breast implant patients. External analyses, using general population rates from the Surveillance, Epidemiology and End Results (SEER) program, resulted in 152.2 cases expected and a standardized incidence ratio (SIR) of 0.9 (95% CI 0.8-1.1). A comparable SIR was found for the other plastic surgery patients (SIR =1.0, 95% CI 0.7-1.2). Internal analyses, directly comparing the implant patients with the other plastic surgery patients, showed a RR of 0.8 (95% CI 0.6-1.1). In neither the external nor internal analyses was there any systematic variation in risk by age or calendar year of initial implant. Risk also did not vary by years of follow-up or by type of implant. Risk was not affected by exclusion of patients who received their implants following surgery for benign breast disease. Although breast tumors tended to be detected at a somewhat later stage among the breast implant than the comparison patients, the difference was not statistically significant, nor was there any significant difference in breast cancer mortality between the two groups. CONCLUSIONS: Breast implants do not appear to alter the risk of subsequent breast cancer.

Adult↗

PubMed2000

Signaling antibodies complexed with adenovirus circumvent CAR and integrin interactions and improve gene delivery.

Current adenoviral (Ad) vectors cannot be targeted to specific cell types due to the widespread distribution of the Ad receptor (CAR). Moreover, CAR and/or internalization receptors (alphav integrins) are absent or present at low levels on some cell types, rendering them resistant to Ad-mediated gene delivery. To address these problems, we have developed a novel vector targeting approach that takes advantage of the common cell signaling pathways initiated by ligation of alphav integrins and growth factor receptors. Recombinant growth factor/cytokines (TNF-alpha, IGF-1, EGF) which trigger phosphatidylinositol-3-OH kinase (PI3K) activation, a signaling molecule involved in adenovirus internalization, were fused to a monoclonal antibody specific for the viral penton base. Ad vectors complexed with these bifunctional mAbs increased gene delivery 10 to 50-fold to human melanoma cells lacking alphav integrins. The bifunctional mAbs also enhanced gene delivery by fiberless adenovirus particles which cannot bind to CAR. Improved gene delivery correlated with increased virus internalization and attachment as well as PI3K activity. The use of bifunctional mAbs to trigger specific cell signaling pathways offers a widely applicable method for bypassing the normal Ad receptors in gene delivery and potentially increasing the selectivity of gene transfer.

Adenoviridae↗

PubMed2000

Routine pharyngeal cultures may not be useful in pediatric victims of sexual assault.

INTRODUCTION: This study was conducted to determine the usefulness of routine pharyngeal cultures in pediatric sexual assault victims. METHODS: A retrospective chart review was conducted to examine incidence data. The study was conducted in a 656-bed tertiary care hospital with 60,000 ED visits and approximately 350 pediatric sexual assault examinations annually. Records of all pediatric sexual assault examinations completed between 12:01 AM January 1, 1994, and 12:01 AM January 1, 1997, were retrospectively reviewed for inclusion. Subjects were included if they were younger than 15 years and had a nonacute examination for a suspected sexual assault. The final sample included 370 females and 81 males (total n=451 children). Oral and anal cultures were obtained on all patients. In addition, female patients had vaginal cultures and male patients had penile cultures performed. Culture specimens were sent for detection of chlamydia and gonococcus organisms. RESULTS: Of the 451 sets of cultures examined, there were 6 patients with one or more positive culture results. The 6 patients yielded a total of 10 positive culture results: 1 anal only, 1 vaginal only, and 4 both anal and vaginal. This was a positive culture rate of 1.3% overall. The positive culture result rates by site were oral 0%, vaginal 1.6%, anal 1.1%, and penile 0%. The ages of patients with positive culture results ranged from 2 to 13 years; all of those with positive culture results were female. DISCUSSION: The incidence of positive oral culture results in this sample was zero. This finding supports a more limited approach to standard sexually transmitted disease screening in pediatric sexual assault victims. The elimination of routine oral cultures in pediatric victims without alleged oral contact decreases the examination time, decreases the number of invasive procedures associated with the examination, and decreases the cost of the examination without negatively affecting patient care.

Adolescent↗

PubMed2000

Characteristics of a population of women with breast implants compared with women seeking other types of plastic surgery.

Several previous studies have shown that breast implant patients demonstrate a number of differences compared with the general population. However, studies have not compared patients with breast implants with women receiving other types of plastic surgery, of interest because this latter group has been proposed as a comparison group for assessing the long-term health effects experienced by breast implant patients. Questionnaire data obtained from 7447 breast implant patients and 2203 patients with other types plastic surgery were collected during the course of a retrospective cohort study, to determine whether implant patients demonstrate different characteristics compared with a more restricted group of patients. In contrast to previous investigations that compared implant patients with the general population, distinctive differences with respect to family income, number of pregnancies, alcohol consumption, cigarette smoking, or histories of previous gynecologic operations or operations for benign breast disease were not found. However, implant patients were significantly more likely than other plastic surgery patients to be white, have low levels of education, have early ages at first birth, be thin, and be screened frequently for breast disease. Furthermore, implant patients reported somewhat greater use of exogenous hormones and familial histories of rheumatoid arthritis. These results support the notion that other plastic surgery patients are a more appropriate comparison group than women in the general population for studies of the health effects of breast implants; however, there continue to be distinctive characteristics possessed by breast implant patients, which need to be taken into account in an assessment of what disease effects can be uniquely attributed to silicone breast implants.

Adult↗

PubMed2000

Prevalence of rupture of silicone gel breast implants revealed on MR imaging in a population of women in Birmingham, Alabama.

OBJECTIVE: Silicone gel breast implants have been reported to rupture, but the prevalence of implant rupture in an unreferred population of women is not known. The objective of this study was to assess the prevalence of implant rupture and the presence of extracapsular silicone gel in an unreferred population of women without regard to the absence or presence of any local or systemic symptoms. SUBJECTS AND METHODS: Women identified as part of a National Cancer Institute cohort study on breast implants, living in the Birmingham, AL, area were invited to undergo MR imaging of their current silicone gel breast implants at the Kirklin Clinic at the University of Alabama at Birmingham. Three radiologists independently examined and rated all MR images for signs of implant rupture and extracapsular silicone. RESULTS: A total of 344 women with silicone gel breast implants underwent MR imaging. Breast implant rupture was reported by at least two of three radiologists for 378 (55.0%) of the 687 implants in this study. Another 50 implants (7.2%) were rated as indeterminate (suspicious) for rupture. A majority of women in this study, 265 (77.0%) of 344, had at least one breast implant that was rated as ruptured or indeterminate. Radiologists also agreed that silicone gel could be seen outside the fibrous capsule that forms around the implant in 85 (12.4%) of the 687 implants affecting 73 women (21.2%). Factors that affected implant rupture were implant age and location (submuscular or subglandular). The median implant age at rupture was estimated to be 10.8 years with a 95% confidence interval of 8.4-13.9 years. CONCLUSION: The prevalence of silent or occult silicone gel breast implant rupture is higher than was previously suspected. Most women in this study had MR imaging evidence of at least one ruptured silicone gel breast implant.

Adult↗

PubMed2000

Limitations of computerized tomography in staging invasive bladder cancer before radical cystectomy.

PURPOSE: Computerized tomography (CT) of the abdomen and pelvis is often routine in the preoperative staging assessment of invasive transitional cell carcinoma of the bladder. We determine the accuracy of staging CT findings, usefulness before planned extirpative surgery and impact on surgical management of this disease. MATERIALS AND METHODS: We retrospectively reviewed the medical records, including radiographic, operative and pathological reports, of 82 consecutive cases. All patients presented with muscle invasive bladder tumors, were considered candidates for radical cystectomy and underwent preoperative staging CT of the abdomen and pelvis between July 1994 and June 1998. The ability of CT to provide additional staging information in terms of depth of tumor invasion, local extent of tumor, pelvic lymph node involvement and distant metastases was examined. We determined whether CT findings altered surgical management for individual patients. RESULTS: CT was able to discriminate depth of invasion in only 1 patient (1.2%) and correctly identified extravesical tumor spread in 4 (4.9%). Lymph node and distant metastases were accurately determined in 4 (4.9%) and 2 (2.4%) cases, respectively. The overall accuracy of CT was 54. 9%, with an under staging and over staging rate of 39.0% and 6.1%, respectively. CT provided accurate, additional staging information in only 8 cases (9.8%). Surgical management was altered in 3 cases (3.7%) and only 1 (1.2%) avoided an unnecessary operation as a result of CT findings. CONCLUSIONS: Staging CT of the abdomen and pelvis in patients with invasive bladder carcinoma has limited accuracy, mainly because of its inability to detect microscopic or small volume extravesical tumor extension and lymph node metastases. CT tends to under stage advanced disease and failed to alter surgical management in nearly all of our cases.

Aged↗

PubMed2000

The effect of union type on psychological well-being: depression among cohabitors versus marrieds.

Marital status is a key determinant of psychological well-being. I use data from both waves of the National Survey of Families and Households to evaluate the effect of union type (i.e., cohabitation versus marriage) on depression. Cohabitors report higher levels of depression than their married counterparts, net of sociodemographic factors. The greater depression characterizing cohabitors is primarily due to their higher relationship instability relative to marrieds. Cohabitors' reports of relationship instability are about 25 percent higher than marrieds' reports. High levels of relationship instability are especially detrimental for cohabitors who have been in their union for a long period of time. Additionally, cohabitors' depression scores are exacerbated by the presence of biological and step children, whereas marrieds' depression scores are impervious to children. Longitudinal analyses that correct for selection bias confirm that the lower levels of well-being characterizing cohabitors are not due to the types of people who choose to cohabit.

Adult↗

PubMed2000

Cadaveric versus autologous fascia lata for the pubovaginal sling: surgical outcome and patient satisfaction.

PURPOSE: We report our initial experience with cadaveric fascia lata in pubovaginal sling procedures. MATERIALS AND METHODS: We compared 121 consecutive women who underwent a sling procedure using cadaveric fascia lata from February 1997 through June 1999 (group 1) with 46 consecutive women who underwent a sling procedure using autologous fascia lata from May 1994 through July 1997 (group 2). RESULTS: Mean followup was longer in group 2 (44 versus 12 months). A total of 104 of the 121 group 1 patients (86%) responded to the questionnaire, of whom 85% were cured of stress incontinence, 83% reported overall improvement in urinary control and 74% had no or minimal leakage not requiring pads. Median catheterization time was 9 days (range 4 to 120). Overall 89% of the women were satisfied with the results and 83% would recommend this surgery. A total of 30 of the 46 group 2 patients (65%) responded to the questionnaire, of whom 90% were cured of stress incontinence, 90% reported overall improvement in urinary control and 73% had no or minimal leakage not requiring pads. Median catheterization time was 14 days (range 6 to 180). Overall 90% of the women were satisfied with the results and 83% would recommend this surgery. CONCLUSIONS: Cadaveric fascia lata pubovaginal slings appear to be safe. Early experience suggests that cadaveric fascia lata may be considered an alternative to autologous fascia. Cadaveric and autologous fascia lata appear to have a high success rate.

Cadaver↗

PubMed1999

Arsenic trioxide causes selective necrosis in solid murine tumors by vascular shutdown.

To investigate the antitumor action of arsenic trioxide in solid tumors, we carried out quantitative tumor perfusion studies, using locally advanced methylcholanthrene-induced fibrosarcoma grown in BALB/c mice. The tumor perfusion studies were assessed by two separate methods: 99mTc clearance and 86Rb uptake. A single administration of arsenic trioxide (10 mg/kg i.p.) produced a preferential vascular shutdown in the tumor tissue at 2 and 6 h, leading to massive necrosis in the central part of the tumor. The phenomenon was repeatable at intervals of weekly administration of the drug in the same tumor. Normal skin, muscle, and kidney were relatively unaffected by arsenic trioxide. These results suggest that the drug may be investigated as an adjunct to the standard cancer therapeutic modalities.

Animals↗

PubMed1999

Fractionated radiosurgery for 9L gliosarcoma in the rat brain.

PURPOSE: Fractionated radiosurgery is being carried out in the clinic to improve the therapeutic ratio of single-dose radiosurgery using various fractionation schemes. Because there is a paucity of experimental radiobiological data in the literature on the tumor response and late-responding normal tissue of critical intracranial structures to radiosurgery, the present animal study was designed to compare the response following a single high dose of radiation with that obtained from calculated fractionated doses of radiosurgery. METHODS AND MATERIALS: Male Fischer rats with 9L gliosarcoma growing in their brains were stereotactically irradiated and assayed for the tumor control rate and brain tissue damage. The radiation dose needed for 50% tumor control (TCD50) was used as the endpoint of the efficacy of radiosurgery. Normal brain damage was measured histologically following a period of time over 270 days. Histological evaluation included hematoxylin-eosin (H & E), Luxol fast blue and periodic acid Schiff (LFB/PAS) for the presence of myelin and glial fibrillary acidic protein (GFAP) for the assessment of astrocytic re-activity. The optical density of optic nerves and chiasms staining with LFB/PAS was quantitatively measured using a computer image analysis to assess the magnitude of demyelination. RESULTS: Radiosurgery (RS) was found to be more effective in curing small tumors than large tumors. The dose required to control 50% of the tumored animals for 120 days was 24, 31, and 40 Gy for 2-, 6-, and 12-day-old tumors, respectively. Using 12-day-old brain tumors, two fractions of 23.5 Gy and three fractions of 18.5 Gy were found to be equivalent to the single dose of 35 Gy for tumor control. For normal brain damages, the visual pathways including optic nerves and chiasm were found to be highly radiosensitive structures. A single dose of 35 Gy produced 100% severe optic neuropathy. The fractionated RS regimens spared substantial optic nerve damage. CONCLUSION: The present data provide a strong radiobiological rationale for the use of fractionated RS in the treatment of tumors located near critical normal structures, including visual pathways. The sparing effect of fractionated RS is greater for late-responding tissues, relative to the rapidly proliferating tumor tissues. This report also characterizes the dose/time tolerance relationship of optic neuropathy after single and fractionated RS.

Animals↗