Cardiovascular effects of 5-HT1A receptor agonists injected into the dorsal raphe nucleus of conscious rats

The aim of this study was to investigate the cardiovascular effects of the 5-HT1A receptor agonists, 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin), flesinoxan and 5-carboxamidotryptamine (5-CT) following injection into the dorsal raphe nucleus of conscious rats. 8-OH-DPAT (0.5-2.5 micrograms), hypotension, bradycardia and flat body posture. In contrast, injection of 8-OH-DPAT (0.5 microgram) into the median raphe nucleus caused no cardiovascular changes or flat body posture. (-)Pindolol (0.5 microgram dorsal raphe nucleus) had little effect on cardiovascular parameters, but significantly attenuated the cardiovascular effects of 8-OH-DPAT (0.5 microgram dorsal raphe nucleus). N-Methylatropine (1 mg/kg i.v.) antagonised the cardiovascular effects of 8-OH-DPAT (0.5 microgram dorsal raphe nucleus), suggesting these were vagally mediated. Both pretreatments also appeared to reduce 8-OH-DPAT-induced flat body posture. The results suggest that 8-OH-DPAT activates 5-HT1A receptors in the dorsal raphe nucleus to cause hypotension and bradycardia.     

Intracranial ependymoma in children: analysis of prognostic factors

Summary Between 1955 and 1986, 25 children (aged 2 weeks to 15 years) were treated for intracranial ependymoma at M.D. Anderson Cancer Center. Nine patients had supratentorial primaries (5 high-grade, 4 low-grade), and 16 had infratentorial primaries (9 high-grade, 7 low-grade). Five patients had gross complete resection and 20 had incomplete resection. Seven patients received craniospinal irradiation (25–36 Gy to the neuroaxis, 45–55 Gy to tumor bed), 12 received local field irradiation (29–60 Gy, median 50 Gy). Five infants had adjuvant chemotherapy without radiotherapy, and 6 children had postradiotherapy adjuvant chemotherapy, and 12 patients had salvage chemotherapy with various agents and number of courses. Eight patients are alive, disease-free and without relapse from 1 year to 12 1/2 years from diagnosis (median 42 months). The primary failure pattern was local recurrence. The data suggest that 1) the long-term cure rate of children with ependymoma is suboptimal; 2) histologic grade may be of prognostic importance for supratentorial tumors; 3) prognosis appears worse for girls and infants under 3 years of age; 4) in well-staged patients routine spinal irradiation could be omitted; 5) the role of adjuvant chemotherapy is unclear. Address for offprints: Shiao Y. Woo, Department of Radiation Oncology, 6565 Fannin, M.S. DB1-37, Houston, Texas 77030, USA     

Salivary gland 99mTc-scintigraphy: a grading scale and correlation with major salivary gland flow rates

Sequential salivary gland scintigraphy with 99mTc-technetium pertechnetate (Tc-99) is a safe, minimally invasive test for study of major salivary glands. However, its relationship to salivary function has not been investigated in detail. We have investigated the relationship between major salivary gland flow rates and Tc-99 scans and developed a new rating scale using scans of a control group with normal salivary function. Salivary flow rates and Tc-99 scans were obtained from healthy, non-medicated subjects (n = 33) and from xerostomic patients (n = 22). There were significant differences between the groups for salivary flow rates and Tc-99 ratings. Significant correlations were found between salivary flow rates and Tc-99 ratings in the control and xerostomic groups. The Tc-99 rating scale proved reliable in assessing salivary dysfunction, and showed a high inter-examiner correlation. These results demonstrate the usefulness of salivary gland scintigraphy in assessing major salivary gland flow rates and the utility of a new rating scale.     

Novel 1,2,4-oxadiazoles and 1,2,4-thiadiazoles as dual 5-lipoxygenase and cyclooxygenase inhibitors.

A series of 1,2,4-oxadiazoles and 1,2,4-thiadiazoles containing a 2,6-di-tert-butylphenol substituent were prepared and evaluated as dual inhibitors of 5-lipoxygenase and cyclooxygenase in rat basophilic leukemia (RBL-1) cells. Several of these compounds show oral efficacy in the rat carrageenan footpad edema (CFE) and mycobacterium footpad edema (MFE) antiinflammatory models, without concomitant gastric ulceration. Structure-activity relationships are discussed. The best compounds (ID40 values in MFE of 3-8 mg/kg po) contain guanidine-derived substituents on the heterocyclic ring.     

Artifacts due to stimulus correlated motion in functional imaging of the brain

To assess the effect of stimulus correlated motion on the appearance of functional magnetic resonance images, conventional visual and motor protocols were each performed by four normal volunteers and an image co-registration technique was used to retrospectively monitor subject motion. In three studies synthetic data sets were constructed from single baseline images using the positional information obtained from the co-registration procedure. Cumulative difference images were then created from both the synthetic and functional image sets. Stimulus correlated motion was detected in all eight studies and the synthetic cumulative difference images showed striking similarities to the equivalent functional images in each case.     

Problems measuring contrast sensitivity in children

A preliminary study measured the contrast sensitivity function (CSF) in 30 children (aged 3 months-5 years). Preferential looking techniques were used to assess CSF to sine wave gratings displayed on one of two screens. To find a meaningful contrast sensitivity procedure we compared the results with a shorter procedure using an edge stimulus. The following problems were encountered: measuring the contrasts required to detect four or five different spatial frequencies took time, resulting in boredom and loss of attention in our subjects; there was poor correlation between CSF and edge detection; an interesting artefact resulted in a plateau rather than a low frequency fall-off in the CSF of five of the children greater than 30 months old. This artefact may have resulted from peripheral rather than central retinal responses and/or motion artefacts in the stimulus onset. A follow up study with 41 additional children aged 3-36 months limited the contrast testing to that of the spatial frequency corresponding to the peak of the CSF. The shortened procedure, plus a lot of encouragement, resulted in higher contrast sensitivities in all but the oldest age group and successful monocular contrast measurements. In order to avoid artefacts arising from peripheral vision, children were encouraged to look at each screen before responding.