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.

Sequential development of ethylnitrosourea-induced neurinomas: morphology, biochemistry, and transplantability.

Sequential evaluations were made of the morphology and biochemistry of trigeminal nerves from control and ethylnitrosourea (ENU)-exposed rats from 1 day to 6 months of age. Distinct increases in cellularity were evident as early as 20 days after exposure to ENU. Corresponding increases in N-acetyl-beta-glucosaminidase and beta-glucuronidase were detected at the same time. Transplantation studies were performed with grossly normal trigeminal nerves from 32-, 63-, and 91-day-old control and ENU-exposed rats. One of eight nerves from the 32-day-old ENU-exposed donors developed into neurinomas at the site of transplantation. No tumors developed from nerves of controls. These results indicate that the early increases in cellularity and acid hydrolase activities represent neoplastic rather than preneoplastic changes.

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.

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.

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.

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)

Inhibition of Na+-K+-activated ATPase activity following experimental spinal cord trauma.

The specific activity of the membrane-bound enzyme, Na+-K+-activated adenosine triphosphatase (ATPase), has been shown to be decreased following experimental impact injury (400 gm-cm) to the spinal cord in dogs. The prompt and significant (p less than 0.01) fall in activity was evident as early as 5 minutes after injury, and remained at 56% to 67% of control for the 1-hour period studied. This decrease was most prominent in the central core of the traumatized segments of spinal cord. Central core samples, excised immediately adjacent to the trauma site, gave values for the Na+-K+-activated enzyme intermediate to those of the trauma and control sites. For these same samples, the activity of the Mg+2-dependent ATPase did not change appreciably. No alterations were observed in the tissue surrounding the zone of maximum injury at these early time periods. The relationship of membrane-bound enzyme alterations to blood flow, clotting mechanisms, and abnormal free radical reactions are briefly discussed.

Effects of scopolamine, pentobarbital, and amphetamine on radial arm maze performance in the rat.

Rats were trained to obtain food pellets from the end of each arm of an eight-arm radial maze. Baseline performance was characterized by very few entries into arms from which the food pellet had already been obtained. In Experiment 1, neither d-amphetamine (0.1-3.0 mg/kg) nor pentobarbital (1.0-10.0 mg/kg) affected choice accuracy, although the rate of arm-entry increased after d-amphetamine and decreased after pentobarbital. Scopolamine (0.1-1.0 mg/kg), on the other hand, reduced both accuracy and the rate of arm entry. In a second experiment, the effects of scopoalmine were replicated using a between-subjects design. Methylscopolamine (0.17, 1.0 mg/kg) was found to have little effect on performance. Multiple response criteria were also compared in the second experiment. Scopolamine was found to affect runs farther out the arm differently than it affected abbreviated arm entrances. A post-trial feeding test was also included to evaluate changes in reinforcer effectiveness, and showed that food continued to be a reinforcer after both scopolamine and methylscopolamine.

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.

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.

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.