Evolution of models to support community and policy action with science: Balancing pastoral livelihoods and wildlife conservation in savannas of East Africa.

We developed a "continual engagement" model to better integrate knowledge from policy makers, communities, and researchers with the goal of promoting more effective action to balance poverty alleviation and wildlife conservation in 4 pastoral ecosystems of East Africa. The model involved the creation of a core boundary-spanning team, including community facilitators, a policy facilitator, and transdisciplinary researchers, responsible for linking with a wide range of actors from local to global scales. Collaborative researcher-facilitator community teams integrated local and scientific knowledge to help communities and policy makers improve herd quality and health, expand biodiversity payment schemes, develop land-use plans, and fully engage together in pastoral and wildlife policy development. This model focused on the creation of hybrid scientific-local knowledge highly relevant to community and policy maker needs. The facilitation team learned to be more effective by focusing on noncontroversial livelihood issues before addressing more difficult wildlife issues, using strategic and periodic engagement with most partners instead of continual engagement, and reducing costs by providing new scientific information only when deemed essential. We conclude by examining the role of facilitation in redressing asymmetries in power in researcher-community-policy maker teams, the role of individual values and character in establishing trust, and how to sustain knowledge-action links when project funding ends.

How separate are the sensory, emotional, and motivational dimensions of pain? A multidimensional scaling analysis.

UNLABELLED: To map the structure of the space generated by verbal descriptors of pain, 41 male college students made pairwise similarity judgments to all possible pairings of 16 words that describe experiences commonly associated with noxious electrical stimulation. Individual Differences Scaling (INDSCAL) yielded four dimensions (D) in the group stimulus space: D-1, Intense to Moderate Experiences, contained two attributes: Strong Sensations and Strong Emotions; D-2, Moderate to Weak Experiences, exhibited two attributes: Moderate Sensations and Moderate Emotions; D-3, Motivational State, possessed two attributes: Pain and Arousal Level; D-4, Sensory Qualities, exhibited two attributes: Pain and Somatosensory Qualities. The interpretation of the dimensions was supported by Preference Mapping (PREFMAP) and by correlations between subject weights and (a) psychological tests and (b) responses to noxious electrical stimuli. CONCLUSION: semantically, the pain attribute or component of the total pain-suffering experience pervades emotional, motivational and somatosensory attributes. Pain is not an independent dimension. This means that a score on a pain rating scale is not a pure measure of the patient's pain, but is heavily influenced in unknown ways by the patient's emotional and motivational state.

Preoperative Multidimensional Affect and Pain Survey (MAPS) scores predict postcolectomy analgesia requirement.

OBJECTIVES: One aim of this study was to evaluate the relation of scores on the Multidimensional Affect and Pain Survey (MAPS) that was administered before surgery to postoperative morphine consumption and patient-controlled analgesia. A second aim of the study was to compare the ability of MAPS administered postsurgery with the commonly used Numerical Pain Rating Scale to predict patient-controlled analgesia behavior. DESIGN: The MAPS questionnaire measures pain, suffering, and well-being. It was administered to patients 1 day before and 1 day after left hemicolectomy for colon cancer. The relations of the two scores to postoperative pain control were determined. PATIENTS: Thirty-four patients in the surgical ward of a general hospital admitted for colorectal cancer surgery participated in this study. RESULTS: High preoperative MAPS scores on sensory and emotional words predicted postoperative morphine dosage, dose presses, and lockout presses. Greater morphine consumption was correlated positively with high presurgery MAPS scores in four of the eight "Suffering" subclusters (Depressed Mood, Anger, Anxiety, and Fear). High presurgery MAPS scores in 13 of the 17 "Sensory Qualities" subclusters (e.g., Bothersome, Intense Pain, Pain Extent, Incisive Pressure, Traction/Abrasion) were correlated positively with lockout presses. Neither the postsurgery MAPS nor the postsurgery Numerical Pain Rating Scale predicted patient-controlled analgesia behavior. CONCLUSION: The emotional states and attitudes of the patients toward pain before surgery are important factors in determining patient-controlled analgesia pressing behavior and postoperative demand for analgesics.

Central poststroke pain and Wallenberg's lateral medullary infarction: frequency, character, and determinants in 63 patients.

UNLABELLED: Central poststroke pain (CPSP) is an infrequently recognized complication of lateral medullary infarction (LMI). We determined the frequency, nature, and predictors of this complication in 63 patients with LMI. The hypothesis tested was that the degree of clinical sensory loss and extent of infarction seen on MRI, both graded by a predetermined scoring scale, would be predictive of CPSP. We also performed quantitative sensory testing (QST) of thermal and pressure sensation thresholds in a subgroup of 19 patients (nine with CPSP and 10 without) to analyze in detail the spinothalamic and trigeminothalamic systems mediating these modalities from both sides of the face and body. We analyzed these results for specific markers of CPSP. RESULTS: CPSP developed in 25% (16/63) of the patients, all within 6 months. This was constant and severe with frequent allodynia, but responded in all cases to amitriptyline and recurred promptly on attempted weaning. CPSP affected the ipsilateral peri-orbital region most commonly, either alone or in combination with the contralateral limbs. Ipsilateral neurotrophic facial ulceration developed in two cases. CPSP correlated significantly (Fisher's exact test, p < 0.0002) with the degree of clinical sensory loss but not with the size of infarction seen on MRI (Fisher's exact test, p = 0.7). QST revealed a highly specific (100%) and sensitive (89%) finding for CPSP-thresholds from the check contralateral to the LMI were normal in eight of nine cases with CPSP and abnormal in all of the 10 cases without CPSP. Abnormalities in the face contralateral to the infarct are referable to the crossed trigeminothalamic tract in the medullary reticular formation medial to the infarcted lateral medulla. We conclude that this argues for the theory that central pain is caused by denervation sensitivity of the "paleo"-reticulothalamic connections due to a selective "neo"-spinothalamic lesion.

Pain assessment in self-injurious patients with borderline personality disorder using signal detection theory.

Signal detection theory measures of thermal responsivity were examined to determine whether differences in reported pain experienced during self-injurious behavior in female patients with borderline personality disorder (BPD) are explained by neurosensory factors and/or attitudinal factors (response bias). Female patients with BPD who do not experience pain during self-injury (BPD-NP group) were found to discriminate more poorly between noxious thermal stimuli of similar intensity, low P(A), than female patients with BPD who experience pain during self-injury (BPD-P group), female patients with BPD who do not have a history of self-injury (BPD-C group), and age-matched normal women. The BPD-NP group also had a higher response criterion, B (more stoical) than the BPD-C group. These findings suggest that 'analgesia' during self-injury in patients with BPD is related to both neurosensory and attitudinal/psychological abnormalities.

Pain and self-injury in borderline patients: sensory decision theory, coping strategies, and locus of control.

Fifteen women with borderline personality disorder who do not experience pain during self-injury were found to discriminate more poorly between imaginary painful and mildly painful situations, to reinterpret painful sensations (a pain-coping strategy related to dissociation), and to have higher scores on the Dissociative Experiences Scale than 24 similar female patients who experience pain during self-injury and 22 age-matched normal women. "Analgesia' during self-injury in borderline patients may be related to a cognitive impairment in the ability to distinguish between painful and mildly painful situations, as well as to dissociative mechanisms.

Extranodal sinus histiocytosis with massive lymphadenopathy: isolated central nervous system involvement mimicking meningioma.

We present the fifth reported case of extranodal sinus histiocytosis with massive lymphadenopathy (SHML) isolated in the central nervous system. This case emphasizes the importance of recognizing the clinical and radiographic presentation of SHML and shows that immunohistochemical evaluation is required for definitive diagnosis.

Effects of cognitive coping skills training on coping strategies and experimental pain sensitivity in African American adults with sickle cell disease.

The present study examined whether training in cognitive coping skills would enhance pain coping strategies and alter pain perception in adults with sickle cell disease (SCD). Sixty-four African Americans with SCD were randomly assigned to either a cognitive coping skills condition (three 45-min sessions in which patients were trained to use 6 cognitive coping strategies) or a disease-education control condition (three 45-min didactic-discussion sessions about SCD). Pain sensitivity to calibrated noxious stimulation was measured at pre- and posttesting, as were cognitive coping strategies, clinical pain, and health behaviors. Results indicated that, compared with the randomly assigned control condition, brief training in cognitive coping skills resulted in increased coping attempts, decreased negative thinking, and lower tendency to report pain during laboratory-induced noxious stimulation.

Hormonal induction of Dopa decarboxylase in the epidermis of Drosophila is mediated by the Broad-Complex.

The 2B5 early puff locus corresponds to the Broad-Complex BR-C) and encodes a family of transcription factors whose members are induced by the molting hormone ecdysone. Mutations in the br subcomplementation group substantially reduce the levels of Dopa decarboxylase (DDC) in the epidermis of mature third instar larvae but not in mature second instar organisms. Enzyme levels are normal in the central nervous system of the two mutants examined. The specificity of these effects suggests that a product of the BR-C locus mediates the rapid appearance of DDC in mature third instar larvae experiencing an elevated titer of ecdysone. The likely identity of this protein has been confirmed by pursuing the observation that the br28 allele caused by the insertion of a P element into the Z2 DNA-binding domain. Both the transcript and a protein carrying this domain are present in the epidermis and a BR-C recombinant protein carrying the Z2 finger binds to the first intron of the Ddc gene. Five binding sites have been identified within the intron by DNAase I footprinting and a core consensus sequence has been derived which shares some identity with the consensus binding site of the Z2 protein to the Sgs-4 regulatory region. Our demonstration that Ddc is a target of BR-C in the epidermis is the first direct evidence of a role for this early gene in a tissue other than the salivary glands. The data reinforce the idea that BR-C, which clearly mediates a salivary gland-specific response to ecdysone, may play a widespread role in the hormone's activation of gene cascades in other target tissues.

Pain responsivity in major depression and bipolar disorder.

Signal detection theory measures of thermal pain responsivity were examined in patients with major depression and bipolar disorder and in control subjects. Patients with major depression had significantly poorer sensory discrimination of painful thermal stimuli than control subjects, but they did not differ from the control subjects in their sensory discrimination of warm thermal stimuli of lower intensity. Patients with bipolar disorder did not differ significantly in sensory discrimination from either the patients with major depression or the control subjects. Patients with major depression had significantly higher (i.e., more stoical) response criteria than the control subjects for the painful thermal stimuli and also for the lower intensity stimuli; patients with bipolar disorder had significantly higher criteria than control subjects for only the lower intensity stimuli. The results suggest that reduced responsivity to pain in major depression may reflect sensory as well as affective abnormalities. Complaints of pain are very common in mood disorders, and continued examination of experimental pain in individuals with these disorders has the potential to enhance our understanding of this phenomenon.

Origins of the parasitic habit in the nematoda.

Circumstances that probably attended and influenced the adoption and development of the parasitic habit amongst the Nematoda are examined. Features that allowed early terrestrial nematodes to exploit discontinuous habitats such as decomposing organic matter, are considered to have been advantageous to microbivorous Secernentea that became parasites of animals and plants. This development followed the appearance of a land flora and that the Amphibia were the first vertebrate hosts of nematodes. Life cycles involving intermediate hosts were essential in drier environments and in a aquatic ones where intermediate hosts preserve the infective stages; keeps them "in circulation", and makes them attractive to predators. It is concluded that the parasitic habit was adopted repeatedly in both Secernentea and Adenophorea, though the latter did not diversify as much. Convergence is a common feature of nematode evolution, and the typical life history pattern of 5 stadia separated by 4 moults is often greatly modified by suppression, extension and diversification of stages and their roles. There is a need to examine the nematodes, especially of invertebrates in the remaining rain forests of Gondwanaland before they disappear.

On the absence of correlation between responses to noxious heat, cold, electrical and ischemic stimulation.

Is a person's response to one noxious stimulus similar to his/her responses to other noxious stimuli? This long-investigated topic in pain research has provided inconclusive results. In the present study, 2 samples were studied: one using 60 healthy volunteers and the other using 29 patients with coronary artery disease. Results showed near-zero correlations between measures of heat, cold, ischemic, and electrical laboratory pains, as well as between these laboratory pains and an idiopathic pain, the latency to exercise-induced angina in the patients. Power analyses showed that the sample sizes were sufficient to detect a correlation of 0.50 or greater at the 0.05 level 99% of the time in the healthy volunteers, and between 80 and 85% of the time in the patients. Reliability analyses indicated retest correlations on the order of 0.60 for these measures, indicating that the lack of correlation between modalities was not due to unreliability within a measure. These studies fail to demonstrate alternate-forms reliability among these tests, and also fail to support the notion that a person can be characterized as generally stoical or generally complaining to any painful stimulus. In practice, this implies that a battery of tests should generally be used to assess pain sensitivity and also that assessments of one pain modality are not generally useful for making inferences about another.

Interstitial iodine 125 and concomitant cisplatin followed by hyperfractionated external beam irradiation for malignant supratentorial glioma. Preliminary experience at the University of Tennessee, Memphis.

Between November 1989 and October 1992, 28 consecutive patients with glioblastoma multiforme (n = 18) or anaplastic astrocytoma (n = 10; includes one patient with oligodendroglioma with anaplastic astrocytoma component) were treated with interstitial iodine 125 (60 Gy over 6 days) and with concomitant cisplatin (via infusion on days 2-6 of the implant), then followed by hyperfractionated external beam irradiation (110 cGy delivered twice daily; 66 Gy planned total dose). Of 26 patients (60%) who received both 125I and HEBI, 15 are alive with no evidence of recurrent disease at a median follow-up of 18 months post-125I (range: 11 to 34 months). Four other disease-free patients succumbed to nontumor-related events. Two patients with local control had distant failure outside the HEBI treatment fields. Overall local control is 77%. Local failure occurred in 6 patients (23%) 2 to 11 months post-125I. Time to disease progression ranged from 4 to 18 months (median: 10 months). Survival (measured from the date of diagnosis) has ranged from 6 to 26 months (median: 15 months). All patients have maintained Karnofsky Performance Status within 20 points of their preimplant status, with the exception of a single patient who, following diagnosis of radiation necrosis and surgical intervention for symptomatic relief, had a 30-point drop in KPS. Radiation necrosis or persistent mass effect were noted by neuroimaging in seven patients, four of whom required surgical intervention following failed medical management. Ototoxicity, nephrotoxicity, peripheral nerve dysfunction, or hematologic toxicities have not been observed. This new innovative treatment approach offers a promising alternative to the normally dismal prognosis for patients with malignant gliomas.

Multidimensional scaling of painful electrocutaneous stimulation: INDSCAL dimensions, signal detection theory indices, and the McGill Pain Questionnaire.

Individual-differences multidimensional scaling (INDSCAL) determined the dimensions underlying ratings of electrocutaneous stimuli, which ranged from innocuous levels to individual pain intolerance at each of three frequencies. Twenty-five healthy males made pairwise similarity judgments of these 15 stimuli for the INDSCAL procedure, and then rated each stimulus on nine property scales. Signal detection theory indices, as well as ratings on the McGill Pain Questionnaire (MPQ), were also obtained. A Sensory Magnitude dimension scaled the stimuli from lowest to highest perceived intensity; this dimension was related to sensory, affective, and arousal property scales. A Frequency dimension ordered the stimuli from lowest to highest frequency; this dimension was related to the Fast-Slow property. Compared to the Frequency dimension, the Sensory Magnitude dimension was more salient to subjects who better discriminated among painful stimulus intensities, set a more stoical pain report criterion, and were less apt to endorse frequency-related MPQ descriptors. Thus, variation of physical intensity and frequency elicited complementary dimensions of subjective judgment, which were related to perceptual and attitudinal differences among individuals.

Expression of the vascular permeability factor/vascular endothelial growth factor gene in central nervous system neoplasms.

Expression of the vascular permeability factor/vascular endothelial growth factor (VEGPF) gene was investigated in human central nervous system (CNS) neoplasms and normal brain. Adsorption of capillary permeability activity from human glioblastoma multiforme (GBM) cell conditioned medium and GBM cyst fluids by anti-VEGPF antibodies demonstrated that VEGPF is secreted by GBM cells and is present in sufficient quantities in vivo to induce vascular permeability. Cloning and sequencing of polymerase chain reaction-amplified GBM and normal brain cDNA demonstrated three forms of the VEGPF coding region (567, 495, and 363 nucleotides), corresponding to mature polypeptides of 189, 165, and 121 amino acids, respectively. VEGPF mRNA levels in CNS tumors vs. normal brain were investigated by the RNase protection assay. Significant elevation of VEGPF gene expression was observed in 81% (22/27) of the highly vascular and edema-associated CNS neoplasms (6/8 GBM, 8/8 capillary hemangioblastomas, 6/7 meningiomas, and 2/4 cerebral metastases). In contrast, only 13% (2/15) of those CNS tumors that are not commonly associated with significant neovascularity or cerebral edema (2/10 pituitary adenomas and 0/5 nonastrocytic gliomas) had significantly increased levels of VEGPF mRNA. The relative abundance of the forms of VEGPF mRNA was consistent in tumor and normal brain: VEGPF495 > VEGPF363 > VEGPF567. In situ hybridization confirmed the presence of VEGPF mRNA in tumor cells and its increased abundance in capillary hemangioblastomas. Our results suggest a significant role for VEGPF in the development of CNS tumor neovascularity and peritumoral edema.

Evidence for the involvement of a potential second tumor suppressor gene on chromosome 17 distinct from p53 in malignant astrocytomas.

Molecular analysis of malignant astrocytomas demonstrated three distinct groups of tumors with chromosome 17p abnormalities, which include (a) deletion of the p53 locus (17p13.1) and mutations in the remaining allele, (b) deletion of the p53 locus but no detectable mutations in the remaining allele, and (c) deletions not including the p53 locus but mutations in one of the alleles. Furthermore, deletion mapping analysis demonstrated allelic loss of genes distal to D17S28/D17S5 markers (17p13.3) in group C tumors. The loss of heterozygosity of genes on chromosome 17 without detectable mutation (group B) or deletion (group C) in the p53 gene implies the presence of a second tumor suppressor gene in the telomeric region of 17p, the homozygous functional inactivation of which may play a role, either alone or in conjunction with p53, in the initiation and/or progression of astrocytic neoplasms.

Clonal composition of glioblastoma multiforme.

Glioblastoma multiforme, the most common and most lethal primary central nervous system neoplasm, is noted for its phenotypic and biological heterogeneity. This heterogeneity may result from genetic alterations accumulated by a single transformed astrocyte as it evolves into a monoclonal tumor. Alternatively, it may be attributed to the presence of multiple biologically and genetically distinct astrocytic populations within a polyclonal tumor. To address the issue of clonal composition of glioblastoma multiforme the authors used two independent approaches: analysis of X-chromosome inactivation and analysis of chromosomes 10 and 17 for tumor-specific somatic deletions. The analysis included 10 tumors from nine female patients with glioblastoma multiforme (eight primary and two recurrent tumors), who were heterozygous at either of two X-chromosome genes (hypoxanthine phosphoribosyl-transferase or phosphoglycerate kinase). Nine glioblastomas multiforme demonstrated a monoclonal pattern on X-chromosome analysis; contamination with normal tissue obscured the analysis in one tumor. Somatic deletions on chromosomes 10 and/or 17 occurred in nine tumors, supporting a monoclonal composition for these tumors. These data suggest that glioblastoma multiforme is a monoclonal neoplasm, derived from the clonal expansion of a single transformed astrocyte that has, as a fundamental step in tumorigenesis, sustained a critical genetic alteration on chromosome 10 and/or 17.

Amplification and/or overexpression of platelet-derived growth factor receptors and epidermal growth factor receptor in human glial tumors.

Analysis of genomic organization and expression of platelet-derived growth factor receptors (PDGFR) and epidermal growth factor receptor (EGFR) in human malignant gliomas showed amplification and overexpression of both receptors in distinct subsets of tumors. Amplification of the alpha PDGFR was detected in 4 of 50 glioblastomas (8%). EGFR was amplified in 9 of the 50 tumors (18%). Western blot analysis showed elevated expression of alpha PDGFR and EGFR proteins in 4 (24%) and 3 (18%), respectively, of 17 tumor specimens analyzed. Increased production of alpha PDGFR as well as EGFR proteins was observed in the presence or absence of gene amplification. Three of the 4 tumors with elevated levels of alpha PDGFR also overexpressed the beta PDGFR, which was present as a single copy gene in all 50 tumors analyzed. Our findings suggest that the amplification and/or overexpression either of EGFR or of the alpha PDGFR along with the coordinate overexpression of the beta PDGFR can contribute to the malignant phenotype of distinct subsets of human glioblastoma.