Cerebral [18 F]T807/AV1451 retention pattern in clinically probable CTE resembles pathognomonic distribution of CTE tauopathy.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disorder most commonly associated with repetitive traumatic brain injury (TBI) and characterized by the presence of neurofibrillary tangles of tau protein, known as a tauopathy. Currently, the diagnosis of CTE can only be definitively established postmortem. However, a new positron emission tomography (PET) ligand, [18F]T807/AV1451, may provide the antemortem detection of tau aggregates, and thus various tauopathies, including CTE. Our goal was to examine [18F]T807/AV1451 retention in athletes with neuropsychiatric symptoms associated with a history of multiple concussions. Here we report a 39-year-old retired National Football League player who suffered 22 concussions and manifested progressive neuropsychiatric symptoms. Emotional lability and irritability were the chief complaints. Serial neuropsychological exams revealed a decline in executive functioning, processing speed and fine motor skills. Naming was below average but other cognitive functions were preserved. Structural analysis of longitudinally acquired magenetic resonance imaging scans revealed cortical thinning in the left frontal and lateral temporal areas, as well as volume loss in the basal ganglia. PET with [18F]florbetapir was negative for amyloidosis. The [18F]T807/AV1451 PET showed multifocal areas of retention at the cortical gray matter-white matter junction, a distribution considered pathognomonic for CTE. [18F]T807/AV1451 standard uptake value (SUV) analysis showed increased uptake (SUVr⩾1.1) in bilateral cingulate, occipital, and orbitofrontal cortices, and several temporal areas. Although definitive identification of the neuropathological underpinnings basis for [18F]T807/AV1451 retention requires postmortem correlation, our data suggest that [18F]T807/AV1451 tauopathy imaging may be a promising tool to detect and diagnose CTE-related tauopathy in living subjects.

Degradation of insecticides used for indoor spraying in malaria control and possible solutions.

BACKGROUND: The insecticide dichloro-diphenyl-trichloroethane (DDT) is widely used in indoor residual spraying (IRS) for malaria control owing to its longer residual efficacy in the field compared to other World Health Organization (WHO) alternatives. Suitable stabilization to render these alternative insecticides longer lasting could provide a less controversial and more acceptable and effective alternative insecticide formulations than DDT. METHODS: This study sought to investigate the reasons behind the often reported longer lasting behaviour of DDT by exposing all the WHO approved insecticides to high temperature, high humidity and ultra-violet light. Interactions between the insecticides and some mineral powders in the presence of an aqueous medium were also tested. Simple insecticidal paints were made using slurries of these mineral powders whilst some insecticides were dispersed into a conventional acrylic paint binder. These formulations were then spray painted on neat and manure coated mud plaques, representative of the material typically used in rural mud houses, at twice the upper limit of the WHO recommended dosage range. DDT was applied directly onto mud plaques at four times the WHO recommended concentration and on manure plaques at twice WHO recommended concentration. All plaques were subjected to accelerated ageing conditions of 40°C and a relative humidity of 90%. RESULTS: The pyrethroids insecticides outperformed the carbamates and DDT in the accelerated ageing tests. Thus UV exposure, high temperature oxidation and high humidity per se were ruled out as the main causes of failure of the alternative insecticides. Gas chromatography (GC) spectrograms showed that phosphogypsum stabilised the insecticides the most against alkaline degradation (i.e., hydrolysis). Bioassay testing showed that the period of efficacy of some of these formulations was comparable to that of DDT when sprayed on mud surfaces or cattle manure coated surfaces. CONCLUSIONS: Bioassay experiments indicated that incorporating insecticides into a conventional paint binder or adsorbing them onto phosphogypsum can provide for extended effective life spans that compare favourably with DDT's performance under accelerated ageing conditions. Best results were obtained with propoxur in standard acrylic emulsion paint. Similarly, insecticides adsorbed on phosphogypsum and sprayed on cattle manure coated surfaces provided superior lifespans compared with DDT sprayed directly on a similar surface.

Models for predicting subjective quality of life in individuals with traumatic brain injury.

The objective of this study was to compare the utility of ICIDH-based models and needs-based models for predicting subjective quality of life in individuals with traumatic brain injury (TBI). Using an existing data base of individuals with TBI living in the community, seven predictive models were tested using multiple regression analyses. In comparing adjusted R2 associated with each of seven models, it was concluded that needs-based models using subjective indicators clearly predict more variance in measures of life satisfaction, or subjective well-being, than do either type of model relying on objective measures. It is suggested that, in documenting 'outcomes' of rehabilitation, the degree to which the focal individual's important needs are met defines more directly his/her well-being than do measures of impairment, disability or handicap.

The sensitivity and specificity of self-reported symptoms in individuals with traumatic brain injury.

In this study, self-reported symptoms (cognitive, physical, behavioural/affective) from the TIRR Symptom Checklist are compared across six panels: 135 individuals with mild TBI, 275 with moderate/severe TBI, 287 with no disability, 104 with spinal cord injury, 197 who are HIV positive and 107 who had undergone liver transplantation. Participants with TBI and SCI were at least 1 year post-injury. Individuals with TBI reported significantly more symptoms than other panels. Symptom reports in the TBI panels were independent of demographic variables (gender, education, income, ethnicity, age), as well as time since injury and depression. Five of the 67 symptoms were found to be sensitive/specific to TBI in general; 25 symptoms were sensitive/specific to mild TBI (23 were cognitive, one physical and one behavioural/affective). Implications of these results in terms of current debates about the 'reality' of symptom reports in individuals with mild TBI are discussed, as well as implications for using symptom checklists for TBI screening.

The unveiling of traumatic brain injury in an HIV/AIDS population.

This study examines the frequency of traumatic brain injury (TBI) in an HIV/AIDS population and its associated symptomatology. A panel of 173 individuals with HIV were split into two groups--those who have experienced a blow to the head within their lifetime (n = 128) and those who have not (n = 45). Self-reported symptoms from the TIRR Symptom Checklist were compared across both HIV panels, individuals who identified as traumatically brain injured (n = 416), and individuals with no disability (n = 282). Six clusters of symptoms (total, cognitive, physical, affective/behavioural, five symptoms sensitive and specific to TBI in general and 25 symptoms sensitive and specific to mild TBI) were analysed in a MANOVA, controlling for the demographic variables that were correlated with total symptoms, including panel membership, education, annual household income and substance use history. Significant main effects were found for panel membership. Individuals with HIV and a history of blow to the head reported a higher number of total symptoms and the 25 symptoms specific to mild TBI. The significance of these findings acknowledges the need to recognize the frequency of TBI in an HIV population and the subsequent need to provide the appropriate interventions that will lead to an enhanced overall quality of life.

Axis II psychopathology in individuals with traumatic brain injury.

PRIMARY OBJECTIVES: To determine the frequency and nature of post-TBI personality disorders (PDs) in a community-based sample of individuals with TBI. RESEARCH DESIGN: One hundred individuals with TBI were administered a structural clinical interview to determine Axis II psychopathology. METHODS OF PROCEDURES: The Structured Clinical Interview for DSM-IV Personality Disorders, Clinician Version (SCID II) was used to determine 12 Axis II personality disorders. SCID II questions were modified so that symptom onset could be rated as occurring pre-injury vs. post-TBI. Data were analysed using student T-tests, chi-square analysis and one way analyses of variance. OUTCOMES AND RESULTS: Pre-TBI PDs were diagnosed in 24% of the sample; antisocial PD and obsessive-compulsive PD were the most common diagnoses. Post-TBI, 66% of the sample met criteria for at least one PD, with PDs independent of TBI severity, age at injury, and time since injury. The most common post-TBI PDs were: borderline, avoidant, paranoid, obsessive-compulsive and narcissistic. Men were more likely to be diagnosed with antisocial PD and narcissistic PD. Individuals with pre-TBI PDs were at greater risk of acquiring additional psychopathology post-TBI. Personality traits endorsed by more than 30% of the sample post-TBI reflected loss of self-confidence, attempts to cope with cognitive and interpersonal failures and negative affect. CONCLUSION: These findings argue against a specific TBI personality syndrome, but rather a diversity of personality disorders reflective of the persistent challenges and compensatory coping strategies developed by individuals post-TBI. Prospective need for clinical assessment, pro-active education and focused treatment approaches are discussed.

Medical rehabilitation length of stay and outcomes for persons with traumatic spinal cord injury--1990-1997.

OBJECTIVES: To describe changes in acute and rehabilitation length of stay (LOS) for persons with traumatic spinal cord injury (SCI), describe predictors of LOS, and explore year-1 anniversary medical and social outcomes. DESIGN: Longitudinal, exploratory study of patients with SCI. SETTING: Eighteen Model Spinal Cord Injury Centers across the United States. SAMPLE: A total of 3,904 persons discharged from the Model Systems between 1990 and 1997 who had follow-up interviews at 1 year postinjury. MAIN OUTCOME MEASURES: Rehabilitation LOS; injury anniversary year-1 presence of pressure ulcers; incidence of rehospitalization; community or institutional residence; and days per week out of residence. RESULTS: Acute rehabilitation LOS declined from 74 days to 60 days. Discharges to nursing homes and rehospitalizations increased between 1990 and 1997. Linear regression showed that lower admission motor Functional Independence Measure (FIM) scores, year of discharge from the Model System, method of bladder management, tetraplegia, race, education, marital status, discharge disposition, and age were related to longer LOS. At first anniversary, logistic regressions revealed that lower discharge motor FIM, injury level, and age were related to the presence of pressure ulcers, rehospitalization, residence, and time spent out of residence. Of those discharged to nursing homes, 44% returned to home by year 1, and these individuals had higher functional status and were younger. DISCUSSION: High functional status is associated with shorter LOS, discharge to the community, and time spent out of residence, indicating efficiency in the system. For 44.4% of individuals one or more of the following outcomes were observed by first year anniversary: rehospitalization; residing in a skilled nursing facility; having pressure ulcers; or infrequently leaving one's residence.

Quality of life as a construct in health and disability research.

Definitional issues that affect the measurement of quality of life (QOL) in health care research are discussed. In reviewing a broad sample of health- and disability-related QOL studies, the authors note several characteristics in which respective approaches to measurement differ: (a) In various measurement tools, QOL has been located either within the insider's (i.e., the person being measured) judgment of the 'goodness' of his or her life or outside this judgment. (b) The insider's and/or outsider's values may hold sway in deciding the elements of life that are relevant to QOL within the measurement process, and in rating the degree of 'goodness' of these life domains. (c) QOL models incorporate domains of items varying in breadth and specificity; and they take either a negative or neutral view of functioning. (d) QOL models vary in their complexity, type of linkage between components, and inclusion (or not) of both the insider's judgment and external predictors of QOL. These distinctions are used by the authors in recommending approaches to QOL measurement suitable for health care research aimed at outcome assessment and description of populations.

Neuropsychologic outcome after deep hypothermic circulatory arrest in adults.

INTRODUCTION: Pediatric patients undergoing prolonged periods of deep hypothermic circulatory arrest have been found to experience long-term deficits in cognitive function. However, there is limited information of this type in adult patients who are undergoing deep hypothermic circulatory arrest for thoracic aortic repairs. METHODS: One hundred forty-nine patients undergoing elective cardiac or thoracic aortic operations were evaluated preoperatively; 106 patients were evaluated early in the postoperative period (EARLY), and 77 patients were evaluated late in the postoperative period (LATE) with a battery of neuropsychologic tests. Seventy-three patients had routine cardiac operations without deep hypothermic circulatory arrest, and 76 patients with deep hypothermic circulatory arrest were divided into 2 subgroups: those with 1 to 24 minutes of deep hypothermic circulatory arrest (n = 36 patients) and those with 25 minutes or more of deep hypothermic circulatory arrest (n = 40 patients). The neuropsychologic test battery consisted of 8 tests encompassing 5 domains: attention, processing speed, memory, executive function, and fine motor function. Data were normalized to baseline values, and changes from baseline were analyzed by analysis of covariance, multivariate logistic regression, and survival functions. RESULTS: In all domains, poor performance or inability to be tested EARLY were significant predictors of poor performance LATE (odds ratio, 5.27; P <.01). Deep hypothermic circulatory arrest of 25 minutes or more and advanced age were significant predictors of poor performance LATE for the memory and fine motor domains. Deep hypothermic circulatory arrest of 25 minutes or more (odds ratio, 4. 0; P =.02) was a determinant of prolonged hospital stay (>21 days). CONCLUSION: Deep hypothermic circulatory arrest of 25 minutes or more and advanced age were associated with memory and fine motor deficits and with prolonged hospital stay.

The Beck Depression Inventory: is it a suitable measure of depression for individuals with traumatic brain injury?

OBJECTIVE: This study examined the relationship between Beck Depression Inventory (BDI) scores and current diagnosis of depression, based on The Structured Clinical Interview for DSM-IV Diagnosis (SCID). DESIGN: Correlation. SETTING: Community-based sample. PARTICIPANTS: 100 individuals with traumatic brain injury (TBI) participated in this study, 25 of whom were diagnosed as depressed and 75 as not depressed at the time of interview. MAIN OUTCOME MEASURES: BDI scores, number of symptoms reported on a symptom checklist and DSM-IV diagnosis of depression. RESULTS: BDI symptoms correlated significantly with the SCID diagnosis of depression (r = .30) but were more strongly related (r = .67) to the number of non-depression-related problems reported, using the TIRR Symptom Checklist, a list of symptoms frequently found post TBI. The BDI had low sensitivity for discriminating depressed from nondepressed individuals (sensitivity = 36% when specificity was set at 80%). These results suggest that for individuals with TBI, high BDI scores may reflect hyperreactivity to post-TBI symptoms to a greater extent than clinical depression. CONCLUSIONS: Further study is needed to (1) understand the physiological, functional, and psychosocial factors that are associated with depression in individuals with TBI; (2) provide the basis for developing better measures of depression; and (3) understand how depression is experienced after TBI.

The benefits of exercise in individuals with traumatic brain injury: a retrospective study.

OBJECTIVE: This study examined the benefits of exercise. DESIGN: A retrospective study. SETTING: A community-based sample. PARTICIPANTS: A sample of 240 individuals with traumatic brain injury (TBI) (64 exercisers and 176 nonexercisers) and 139 individuals without a disability (66 exercisers and 73 nonexercisers). MAIN OUTCOME MEASURES: Scales measuring disability and handicap. RESULTS: It was found that the TBI exercisers were less depressed than nonexercising individuals with TBI, TBI exercisers reported fewer symptoms, and their self-reported health status was better than the nonexercising individuals with TBI. There were no differences between the two groups of individuals with TBI on measures of disability and handicap. CONCLUSIONS: The findings suggest that exercise improves mood and aspects of health status but does affect aspects of disability and handicap.

Undiagnosed health issues in individuals with traumatic brain injury living in the community.

OBJECTIVES: To examine the self-reported prevalence of long-term health issues in individuals with traumatic brain injury (TBI) living in the community. DESIGN: A structured health interview. For individuals with TBI, the presence of a specific health-related issue with onset post-TBI and currently a problem at the time of the interview was explored. For individuals without disability, a specific health-related issue was evaluated at time of interview. For each health issue, the proportion of individuals with TBI experiencing post-TBI onset but current symptoms was contrasted with symptom reports of individuals without disability. Chi-square statistical analyses were used to determine significance. For individuals with TBI, logistic regressions were used to model the probability of having a particular health difficulty when four covariates were examined, such as age, gender, time since onset of TBI, and duration of loss of consciousness (LOC). SETTING: Urban, suburban, and rural New York State. PARTICIPANTS: 338 individuals with TBI and 273 individuals without disability between the ages of 18 and 65 years. Individuals with TBI were, on average, 10 years post-onset at the time of interview. MAIN OUTCOME MEASURES: Self-reported health issues reflective of neuroendocrine, neurological, immunosuppression, and other health issues. RESULTS: Chronic health issues suggestive of ongoing neuroendocrine dysfunctions (ie, changes in hair/skin texture, body temperature changes), neurologic difficulties (ie, headaches, seizures, balance difficulties, spasticity, sleep disturbances, loss of urinary control), and arthritic complaints were significantly more common in individuals with TBI. The prevalence of many of these health-related difficulties was related to duration of LOC but not to time since injury. Age and gender effects were found, with older women with TBI more likely to report thyroid conditions, sleep disturbances, loss of urinary control, and arthritic changes. Women also reported greater frequency of headaches, colds, weight changes, and temperature changes post TBI. CONCLUSION: Health issues reflective of neuroendocrine, neurological, and arthritic difficulties are common long-term health issues for individuals with TBI. Proactive patient education, ongoing health screening with appropriate medical follow-up, and timely interventions for individuals with TBI are indicated. Longitudinal studies are necessary to examine the natural course of post-TBI health difficulties.

The enigma of "hidden" traumatic brain injury.

OBJECTIVE: To examine individuals with "hidden" traumatic brain injury (TBI), defined in this study as those who sustained a blow to the head, with altered mental status, and experienced a substantial number of the cognitive, behavioral, and emotional sequelae typically associated with brain injury but did not make the causal connection between the injury and its consequences. DESIGN: Comparison of four groups of individuals matched for age, gender, years of education, and duration of loss of consciousness. SETTING: This study of hidden TBI followed the identification of 143 individuals who, within a larger study of people with TBI who live in the community, identified themselves as "nondisabled" (they were to be part of the comparison sample) but who had experienced a blow to the head that left them at minimum dazed and confused. PARTICIPANTS: 21 of these 143 individuals also reported large numbers of symptoms (eg, headaches, memory problems) associated with TBI. This group (Hidden TBI-High Symptoms group) was compared to three other matched samples: one with known TBI (Known Mild TBI group) and one with no disability (No Disability group) (both of which were drawn from the larger study), and one group of individuals who identified themselves as having no disability but who had experienced a blow to the head that resulted in a few symptoms (Head Trauma-Low Symptoms group). MAIN OUTCOME MEASURES: All study participants were administered an interview that incorporated several existing instruments documenting levels of reported symptoms, emotional well-being/distress, and vocational/social handicaps. RESULTS: The Hidden TBI-High Symptoms group was found to be similar to the Known Mild TBI group in terms of the number and types of symptoms experienced, whereas the Head Trauma-Low Symptoms group was similar in this respect to the No Disability group. The two former groups also evidenced high levels of emotional distress, whereas the two latter groups did not. However, on measures of handicap, the Hidden TBI-High Symptoms and Head Trauma-Low Symptoms groups were similar to the No Disability group and dissimilar from the Known Mild TBI group in that the last group experienced vocational handicap, in particular, whereas the other groups did not. CONCLUSIONS: We conclude that hidden TBI occurs at a nontrivial level (7% of our nondisabled sample). Also, individuals with hidden TBI (with persistent symptoms), unlike those with known mild TBI, are likely to experience emotional distress but not vocational handicap following injury.

Parathyroid hormone suppression in spinal cord injury patients is associated with the degree of neurologic impairment and not the level of injury.

OBJECTIVE: To demonstrate that after spinal cord injury (SCI) suppression of the parathyroid-vitamin D axis is associated with the degree of neurologic impairment and not the level of injury. DESIGN: A retrospective analysis of clinical and biochemical data obtained from hospital records of patients with SCI compared to a control group of patients with traumatic brain injury (TBI). SETTING: The inpatient rehabilitation unit of a tertiary care hospital. SUBJECTS: The medical records of 82 consecutive admissions to the rehabilitation unit with a diagnosis of SCI or TBI were reviewed. Patients with SCI were classified by the American Spinal Injury Association (ASIA) impairment scale and then grouped based on the completeness and level of injury. MAIN OUTCOME MEASURE: Comparisons of serum parathyroid hormone (PTH), 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D (1,25-D) were planned. Multiple comparisons were performed for total and ionized serum calcium levels, serum phosphorus levels, and 24-hour urinary calcium excretion rates to reflect changes in mineral homeostasis. Multiple comparisons were also performed for serum albumin, prolactin, thyroid function tests, and AM cortisol levels, as well as 24-hour urinary urea nitrogen and cortisol excretion rates to reflect metabolic responses to stress. RESULTS: Patients with SCI had significant suppression in PTH (p < .000009) and 1,25-D (p < .02) levels with elevated phosphorus (p < 0.03) and prolactin (p < .03) levels compared to patients with TBI. Also, more patients with SCI were hypoalbuminemic (p < .003) than patients with TBI. Patients with complete SCI (ASIA A) had more suppressed PTH (p < .03) and higher urinary urea nitrogen (p < .05) levels than SCI patients with incomplete injuries (ASIA B-D). Patients with complete, but not incomplete, SCI had lower albumin levels than patients with TBI (p < .05). These differences were not found between patients with tetraplegic and paraplegic SCI. ASIA motor scores did not correlate with any of the measured parameters but when used as a covariate did abolish differences in PTH and 1,25-D among the study groups by ANOVA. CONCLUSION: In patients with SCI, the degree of neurologic impairment, and not the level of injury, is associated with PTH suppression and markers of metabolic stress.

Helplessness, self-efficacy, cognitive distortions, and depression in multiple sclerosis and spinal cord injury.

The aim of this study was to determine if learned helplessness, self-efficacy, and cognitive distortions would predict depression in a sample of 80 individuals with multiple sclerosis (MS) and 80 individuals with a spinal cord injury (SCI). As MS and SCI usually present with disparate disease courses and etiologies, a secondary objective was to determine if individuals with MS would exhibit greater levels of helplessness, cognitive distortions, and depression and lower levels of self-efficacy than those with SCI. Results indicated that helplessness and self-efficacy significantly predicted depression for both the MS and SCI groups after controlling for confounding variables. Cognitive distortions had no independent effect, indicating that cognitive distortions may have caused feelings of helplessness and low self-efficacy and, in this way, had indirect effects on depression. The MS group exhibited significantly greater levels of depression and helplessness and significantly lower levels of self-efficacy than the SCI group. It was hypothesized that it may have been the combination of an unpredictable course of disease activity and the possibility of being affected by MS in many different ways that produced greater feelings of depression, helplessness, and low self-efficacy in the MS group.

Poststroke depression: an examination of the literature.

OBJECTIVE: To examine literature on poststroke depression (PSD). DATA SOURCES: More than 200 articles related to stroke and depression were selected from a computer-based search spanning 1985 to 1995. STUDY SELECTION: All relevant articles on PSD. Articles in foreign languages, case studies, anecdotal reports, book chapters, and reviews were excluded. DATA EXTRACTION: Summary findings were independently reviewed by the authors. DATA SYNTHESIS: PSD remains a frequent sequela of stroke; its prevalence remains uncertain because of continued methodologic problems in defining subject groupings and in utilizing psychiatrically normed assessment tools with neurologically impaired individuals, and because of the poor specificity/sensitivity of neuroendocrine markers in determining a diagnosis. The etiology of PSD appears to be complex and not fully understood. Although there has been much research on PSD, this review highlights the sparsity of available literature on its treatment. CONCLUSION: The review points out the further need for more carefully designed studies of PSD that examine both assessment and treatment.

An examination of the needs of families with a brain-injured child.

Data from a questionnaire designed to assess the long-term needs of caregivers of children with brain injury were analyzed. The goals of this study were (1) to identify those needs most important to caregivers, (2) to identify those important needs that were least likely to be met, and (3) to identify characteristics of caregivers that predicted success in having needs met. Caregivers tended to endorse needs focused on acquiring information regarding their child's condition more often than needs to obtain resource or emotional support. On the average, 22 of the 39 needs sampled were considered important to caregivers, while only an average of 9 needs were rated as being met. While there were no strong demographic predictors of success in having important needs met, a regression analysis indicated that respondent gender and age, the number of behavioral problem, exhibited by the brain-injured child, and the Family Crisis Oriented Personal Evaluation Scales (FCOPES) reframing subscale were related to having important needs met. This study indicates that there are significant gaps between what caregivers perceive as important needs and the extent to which caregivers perceive their needs being met.

Utility of the dexamethasone suppression test in the diagnosis of poststroke depression.

The utility of the dexamethasone suppression test (DST) in the diagnosis of depression was examined in an outpatient sample of 29 stroke patients. Results indicated that the DST's sensitivity was 15%, its specificity was 67%, and its positive predictive value was 48%. These findings suggest that the DST yields no more information than would be gained from random assignment of the diagnosis of depression. Therefore, it is not a useful measure of mood in these patients.

Adoptive immunotherapy of a rat glioma using lymphokine-activated killer cells and interleukin 2.

The aim of the present study was to develop an animal model to test the therapeutic potential of purified adherent lymphokine-activated killer (A-LAK) cells against an intracerebrally implanted rat glioma, designated F98. Highly purified A-LAK cells demonstrated greater activity against F98 tumor cells than conventional lymphokine-activated killer cells, as determined by means of 51Cr-release and clonogenic assays. Therapeutic efficacy was evaluated by means of a Winn neutralization assay, in which F98 targets and A-LAK cells or control nonadherent mononuclear cells were incubated for 18 h in vitro and then implanted stereotactically into the right caudate nuclei of Fischer rats. Animals given injections of 4000 F98 cells alone or control nonadherent mononuclear cells had a mean survival time of 22.3 days, compared to 46.1 days (P less than 0.001) for rats treated with A-LAK cells. Increasing the tumor inoculum to 12,500 cells reduced the survival time of A-LAK-treated animals to 27.8 days, compared to 20.8 days for untreated controls. Systemic administration of 50,000 units/kg of interleukin 2 every 12 h for 5 days failed to improve survival. The mean survival time of rats implanted with the F98 tumor ranged from 16 days for 10(5) cells to 29 days for 10(2) cells. Extrapolating from these survival data, treatment with A-LAK cells may have decreased the number of F98 cells to less than 10, but even this small number was still lethal. Supernatants from F98 cells had immunoinhibitory activity that, further, may have modulated the antitumor effects of A-LAK cells. Our results indicate that curative, adoptive immunotherapy of the F98 glioma by means of A-LAK/interleukin 2 is impossible to achieve and provide some explanation for the clinical failures that have been observed in the adoptive immunotherapy of malignant gliomas.

Boron neutron capture therapy of a rat glioma.

The purpose of the present study was to utilize a well-established rat glioma to evaluate boron neutron capture therapy for the treatment of malignant brain tumors. Boron-10 (10B) is a stable isotope which, when irradiated with thermal neutrons, produces a capture reaction yielding high linear energy transfer particles (10B + 1nth----[11B]----4He(alpha) + 7Li + 2.79 MeV). The F98 tumor is an anaplastic glioma of CD Fischer rat origin with an aggressive biological behavior similar to that of human glioblastoma multiforme. F98 cells were implanted intracerebrally into the caudate nuclei of Fischer rats. Seven to 12 days later the boron-10-enriched polyhedral borane, Na2B12H11SH, was administered intravenously at a dose of 50 mg/kg body weight at varying time intervals ranging from 3 to 23.5 hours before neutron irradiation. Pharmacokinetic studies revealed blood 10B values ranging from 0.33 to 10.5 micrograms/ml depending upon the time after administration, a T1/2 of 6.2 hours, normal brain 10B concentrations of 0.5 microgram/g, and tumor values ranging from 1.1 to 12.8 micrograms/g. No therapeutic gain was seen if the capture agent was given at 3 or 6 hours before irradiation with 4 x 10(12) n/cm2 (10 MW-min; 429 cGy). A 13.5-hour preirradiation interval resulted in a mean survival of 37.8 days (P less than 0.01), compared to 30.5 days (P less than 0.03) for irradiated controls and 22.1 days for untreated animals.(ABSTRACT TRUNCATED AT 250 WORDS)