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.

Venom neutralization by rattlesnake serum albumin.

The blood serum of the eastern diamond back rattlesnake (Crotalus adamanteus) neutralizes lethal doses of C. adamanteus venom in mice. The protective capacity of the serum is associated with the serum albumin, rather than the immunoglobulin fraction of the blood. Neither the serum nor its albumin fraction form precipitin bands on immunophoresis against venom.

Acupunctural analgesia? Evaluation by signal detection theory.

Pain responses to noxious thermal stimulation decreased in the acupunctured arm of subjects as compared to the arm not treated with acupuncture; this result suggested that effective analgesia had been induced. However, sensory decision theory analysis of the data revealed no difference in discriminability. This failure to find a sensory (physiological) change strongly suggests that analgesia had not been induced. The sole effect of acupuncture was to cause the subjects to raise their pain criterion in response to the expectation that acture works.

Pain responses in Nepalese porters.

When tested by the method of limits, Nepalese had much higher pain thresholds to electrical stimulation than Occidentals did. Discriminability was the same for both groups, however, indicating that there were no neurosensory differences. Nepalese had higher (stoical) criteria for reporting pain but were not less sensitive to noxious stimulation. The battery of sensory measurement procedures described may be applied to any modality and are particularly applicable to difficult field conditions.

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.

Reduced systemic drug exposure by combining intraarterial cis-diamminedichloroplatinum(II) with hemodialysis of regional venous drainage.

During cancer chemotherapy toxicity to normal tissues often limits the tolerable dose. To increase drug delivery to tumor while maintaining tolerable systemic exposure, regional treatments, such as intraarterial drug delivery, have been used. Despite intraarterial delivery, systemic toxicity often remains the dose-limiting sensitivity. If systemic drug exposure could be reduced after intraarterial infusion, the intraarterial dose could be increased, which should increase the therapeutic response. We compared the pharmacokinetic advantage after cisplatin infusion into the internal carotid artery to that obtained after infusing cisplatin into the internal carotid artery during extracorporeal removal of cisplatin from the jugular blood by hemodialysis. Four patients with malignant gliomas received intracarotid cisplatin, 100 mg/m2 over 60 min, every 4 weeks. During one treatment, while cisplatin was infused into the internal carotid artery, the jugular blood was dialyzed extracorporeally at 300 ml/min and returned to the inferior vena cava. Seventy to 96% of the free platinum that entered the dialyzer was removed. By aspirating blood from the jugular vein at 300 ml/min, 30-79% of the ipsilateral carotid blood was collected for extracorporeal circulation. Hemodialysis of the cerebral venous drainage during intracarotid infusion reduced the systemic exposure to cisplatin by 51-61% when compared to the exposure from internal carotid artery infusion without hemodialysis. The pharmacokinetic advantage (brain/body exposure ratio) was increased from 3 to 5/1 during internal carotid artery infusion alone to as much as 15/1 during treatment combining intracarotid infusion with hemodialysis of the jugular blood. Systemic toxicity now limits the dose of cisplatin that can be administered safely. Increased tumor exposure without increased systemic toxicity may be possible with the technique described and greater doses of cisplatin. Assuming no associated local toxicities, the results of the current study indicate that the dose of intracarotid cisplatin can be increased while maintaining tolerable systemic exposure.

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.

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.

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.

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.

Altered pain and visual sensitivity in humans: the effects of acute and chronic stress.

In the runner study, as measured by tourniquet ischemic pain, exercise stress produced hypoalgesia 20 minutes post-run, followed by hyperalgesia and euphoria at 30 minutes. The hypoalgesia and euphoria were reversed by naloxone. Exercise stress also produced a decrease in P(A), suggesting hypoalgesia to the thermal cutaneous stimulation. However, this analgesia was not naloxone reversible. Nor did exercise stress produce analgesia to cold-pressor pain. In the acupuncture study, noxious electrical stimulation of classical acupuncture sites failed to produce analgesia either during or after stimulation. However, expectation did produce a change in the pain report criterion, but only in the acupunctured arm. Noxious electrical stimulation (TENS) of the median nerve produced no analgesia outside of the related segmental area, that is, acute electrical pain did not produce generalized hypoalgesia. Thus, the effects of the stress produced by noxious electrical stimulation differ from that produced by exercise. In contrast to the results of the acute pain studies, chronic clinical pain, which combines mental stress and pain stress, produced strong hypoalgesia and anesthesia. Again, in contrast to the acute experimental pain studies, the emotional stress of mental illness produces hypoalgesia, but not anesthesia. Finally, the somatosensory system is not the only the sensory system affected by stress. Cold-pressor pain decreases visual sensitivity both during and for a few minutes following stimulation, and does not interfere with short-term (supra-digit span) memory.

Effects of moderate and high doses of marihuana on thermal pain: a sensory decision theory analysis.

Sixteen habitual marihuana users, selected for their good mental and physical health, were hospitalized for three months in the New York State Psychiatric Institute. During the first month, the subjects were drug free; during the second month, they smoked marihuana cigarettes provided by NIDA (2% THC, 20 mg per cigarette) at the rate of 3 to 12 a day. A modified Hardy-Wolff dolorimeter was used to present 20 thermal stimuli of 30-second duration in a random manner at nine different intensities. Subjects responded from a 14-category scale, and data were analyzed according to sensory decision theory analysis. During the third month, the subjects were again drug free. At the noxious thermal intensities, there was a decrease in the pain report criterion during the first two weeks of smoking. The pain enhancement effect was followed by return to the presmoking pain level during weeks 3 and 4 and in the postsmoking period, indicating that tolerance had developed. There was also an increase in pain discriminability during the four weeks of smoking which extended for one week after smoking. Tolerance developed to the pain report criterion but not to the thermal discriminability. This study suggests that marihuana may have hyperalgesic activity and probably enhances the perception of pain, in moderate smokers. In contrast, heavy smoking had little effect on discriminability and caused an increase in the pain report criterion.

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.

High resolution computed tomographic scanning in the detection of intratemporal neuromas of the facial nerve.

Continued refinements in the technique of high resolution computed tomographic scanning now allow the study of the pathology of intratemporal tumors of the facial nerve. The normal anatomy of this area and a selected case of facial nerve neuroma diagnosed with high resolution computed tomography are presented.

Use of the carbon dioxide laser in the operative management of intracranial meningiomas: a report of twenty cases.

This study presents 20 cases of meningioma of various intracranial locations, all of which were removed with the carbon dioxide surgical laser system. The carbon dioxide laser is contrasted with other means of meningioma removal to emphasize the advantages of this new technology. These advantages include: (a) the ability to operate with smaller exposures, (b)reduced brain retraction, (c) a reduced amount of mechanical manipulation by vaporizing the tumor mass, (d) vaporization of the dural attachment after the removal of tumor, (e) improved operative precision, and (f) decreased intraoperative significant advancement in the ability to remove meningiomas that might prove difficult to extirpate by conventional means.

Use of the carbon dioxide laser for acoustic tumor surgery.

The carbon dioxide laser has been used clinically in both otorhinolaryngology and neurological surgery for approximately 10 years. Only recently, however, have technical modifications allowed its use with the operating microscope, providing the increased precision and control necessary for intracranial surgery. This paper reports the authors' experience with the carbon dioxide laser in the removal of acoustic tumors, details the surgical technique involved, and describes the advantages that may accompany the use of the laser in the removal of these difficult lesions.

Mycobacterium tuberculosis meningitis: a report of twelve cases and a literature review.

Twelve recent cases of Mycobacterium tuberculosis meningitis were presented, and the literature was reviewed. There are no particularly new or unique therapies or approaches to the management of this most serious disease. The major obstacle to successful diagnosis and treatment of tuberculous meningitis continues to be a lack of clinical suspicion of its presence. As illustrated in the cases presented, it has been our experience that patients already moribund or nonresponsive do not respond, regardless of the intervention undertaken. The most sensitive and economical method of detecting M. tuberculosis in the CSF may be LPA. However, this has not yet been widely validated or accepted. Larger volumes of CSF should be sent to the laboratory for testing and centifuged to about 5x concentrations before both acid-fast bacilli staining and culture are attempted. If tuberculous meningitis is suspected, three-drug therapy can be started immediately without jeopardizing subsequent culture confirmation of the presence of the TB bacillus. In addition, these patients must be followed closely to detect hydrocephalus at the earliest possible moment. When patients fail to respond to appropriate antituberculosis and pressure-reducing therapy, hydrocephalus should be actively sought by either CT or radioisotope cisternography. Although the decision to proceed to ventricular drainage or shunting must be individually made in adult patients with infection-related hydrocephalus, we agree with others that surgical intervention should be considered early and should be performed if the level of consciousness deteriorates, intracranial pressure increases, or ventricular enlargement or enhancing basal exudates are identified on CT.