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Biomedical subjects

P Dean

Publications and source records attributed to P Dean.

At least 91 records · Page 5Linked to original sources

Clinical and electrophysiological responses to dietary challenge in migraineurs.

Thirty eight patients with a history of diet-induced migraine were studied with recording of clinical responses, electroencephalography in resting state, in response to photic stimulation, and to hyperventilation and visual evoked potentials. Tests were carried out on an initial baseline day and on a second day, after challenge with chocolate, red wine, cheese, and fasting. Lateralized headache occurred in sixteen subjects (42%), four with scintillating scotomata. Electroencephalograms were abnormal on Day 1 and/or Day 2 in twelve subjects (32%), most abnormalities being non-specific slow waves. In three cases there were paroxysmal features. Electroencephalographic response to hyperventilation was calibrated and was found to be exaggerated in eight subjects (21%) on either Day 1 or Day 2; such response was not related to the occurrence of a headache. Photic simulation showed high frequency driving response (so called "H" response) in all 16 individuals who developed headache but in only 14 out of 22 (64%) who did not (p less than 0.01). Pattern reversal visual evoked responses were normal and failed to show any difference in latency or amplitude between headache responders and non-responders.

Adolescent↗

Intratectal glutamate suppresses pentylenetetrazole-induced spike-and-wave discharges.

Cortical spike-and-wave discharges evoked in rats by low (20-50 mg/kg) doses of subcutaneous pentylenetetrazole were suppressed by bilateral microinjection of sodium L-glutamate (100 mM, 200 nl/side) into the superior colliculus. Injections of saline into the superior colliculus, or glutamate into overlying cortex, were ineffective. This result is predicted by the hypothesis that the antiepileptic effects of nigral inactivation are at least partly mediated by the inhibitory nigrotectal pathway that runs from substantia nigra pars reticulata to the superior colliculus.

Animals↗

Detection of visual stimuli after lesions of the superior colliculus in the rat; deficit not confined to the far periphery.

The visual neglect which follows lesions of the superior colliculus in the rat is well documented, although its nature has been somewhat contentious. Recently, using large, bright stimuli, Overton et al. [Exp. Brain Res., 59 (1985) 559-569] presented evidence that collicular lesions produce a detection deficit in the far peripheral visual field (120 degrees), whilst the central field is unaffected. However, some simple tests for visual neglect by other workers suggest that a detection deficit may also exist in the central field, if the stimuli are dim (and small). This possibility was investigated psychophysically. Using a signal detection paradigm, sensitivity to small (2.5 degrees v.a.), transient (modal duration 200 ms) stimuli of varying luminance was determined at 40 degrees on either side of the vertical meridian, before and after collicular lesions or control lesions of the striate cortex. Despite extensive preoperative training, collicular animals showed a decrease in sensitivity of around 50% for all stimulus intensities postoperatively. This deficit was significantly more severe than that produced by striate lesions. Furthermore, it proved very difficult to retrain the animals to a preoperative criterion. These data suggest that collicular lesions do indeed cause a detection deficit which is not confined to the far periphery, and that this deficit may specifically affect the detection of small stimuli. The proposed detection deficit is related to recent anatomical findings in the rat.

Animals↗

Plasticity of behavioural response to repeated injection of glutamate in cuneiform area of rat.

Whereas a single microinjection of L-glutamate (10 nmol) into the cuneiform area of rats gives freezing, a second or third injection (delivered at 4-min intervals to the same site)can produce fast running. To examine whether this plasticity of response was caused by a simple increase in the amount of glutamate present, 30 nmol of glutamate were given in a single injection. In 93% of sites in the cuneiform area this procedure gave only freezing, although subsequent testing with repeated injections produced fast running in 53% of these sites. Thus, response potentiation to glutamate appears to require repeated stimulation, and may therefore be related to processes underlying the natural conditioning of defensive responses.

Animals↗

The projection from superior colliculus to cuneiform area in the rat. I. Anatomical studies.

Although the ipsilateral descending pathway is a major output projection of the superior colliculus, little is known of its functions. We therefore carried out two studies to investigate in rats the part of the ipsilateral projection that terminates in an area ventral to the inferior colliculus, referred to as the cuneiform nucleus. The first study, described here, used orthograde and retrograde tract-tracing techniques to locate the cells of origin and precise region of termination of the tectocuneiform pathway. The main findings were as follows. Injections of WGA-HRP into the superior colliculus gave terminal label in the cuneiform nucleus and also in surrounding structures which included central grey, the midbrain tegmentum bordering the parabigeminal nucleus, and the external nucleus of the inferior colliculus. As well as the strong ipsilateral projection, there was a much weaker contralateral one which crossed the midline in the tectal commissure. Label in the cuneiform nucleus was heaviest after injections into the medial deep layers. However, no clear evidence was found for topography within the tectocuneiform projection: cuneiform label varied in intensity rather than pattern of distribution with variation in the collicular location of the injection site. Injections of retrograde tracers into the cuneiform are a labelled large numbers of collicular cells, which were distributed mainly in the deep and intermediate grey layers. In agreement with the data from orthograde tracing, the heaviest concentration of labelled cells was found in the medial deep layers. This concentration extended into the adjacent dorsolateral part of central grey. A similar distribution of labelled cells was seen after injections into the structures next to the cuneiform nucleus that also receive a tectal projection. Comparison of this distribution with that obtained from injections into other parts of the ipsilateral projection, including dorsolateral basilar pons, suggested that the projection to the cuneiform area may arise from a distinct set of collicular output cells. The projection from the superior colliculus to the cuneiform nucleus and immediately adjacent areas may therefore be also functionally distinct, mediating a particular kind of tectally-elicited response. The lack of clear topography in the projection suggests that this response may not have precise spatial direction.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

The projection from superior colliculus to cuneiform area in the rat. II. Defence-like responses to stimulation with glutamate in cuneiform nucleus and surrounding structures.

To investigate the role of the projection from superior colliculus to the cuneiform nucleus in mediating collicular responses, the cuneiform area (including the cuneiform nucleus and immediately adjacent structures such as caudal central grey) was stimulated in rats with microinjections of glutamate (50 mM, 200 nl, 10 nmole) and the animals' head and body movements observed. The most common responses obtained from sites in the cuneiform area were freezing, darting or fast running, the form or direction of which did not appear to be strongly influenced by the laterality of the injection. These responses were only a subset of those that have been obtained in previous studies from stimulation of the superior colliculus itself: stimulation of the cuneiform area did not give contralaterally directed movements resembling orienting or approach, or ipsilaterally directed movements resembling cringing or shying. It therefore appears that the tectocuneiform projection is likely to be involved only in some of the behaviours appropriate to unexpected stimuli that are mediated by the superior colliculus, namely undirected defensive responses elicited normally by certain kinds of threatening or noxious stimulation. Involvement with such responses would be consistent with an apparent lack of topography in the tectocuneiform projection, and the connections of the cuneiform nucleus with parts of the brain concerned with nociception (see previous paper). It is unclear, however, whether the somatic responses occur in parallel with, or as a result of, autonomic changes that have also been evoked by stimulation of the cuneiform area. One striking feature of stimulating the cuneiform area with glutamate was that at many sites the intensity of the response appeared to increase with successive (one to three) injections. It is possible that this plasticity of response, which can also be obtained from the superior colliculus itself, is related to processes involved in sensitisation or learning of defensive responses.

Animals↗

Contralateral head movements produced by microinjection of glutamate into superior colliculus of rats: evidence for mediation by multiple output pathways.

One of the major efferent pathways of the superior colliculus crosses midline to run caudally in the contralateral predorsal bundle, innervating targets in the brain stem and eventually reaching the cervical spinal cord. A variety of evidence suggests that this tecto-reticulo-spinal pathway may mediate the orienting movements that can be evoked by tectal stimulation. However, we have recently found that orienting head movements can still be obtained in rats after section of the tecto-reticulo-spinal pathway, implying that additional pathways are also involved. The present study sought to test this implication, by taking advantage of the fact that in rats the cells of origin of the tecto-reticulo-spinal pathway are largely segregated within the lateral part of the stratum album intermediate. It is thus possible to find out whether orienting head movements can be produced by a cell-excitant from tectal regions that contain few cells of origin of the tecto-reticulo-spinal pathway. Hooded rats in an open field were filmed during microinjections of sodium L-glutamate (50 mM, 200 nl) into the superior colliculus, and the films analysed for the appearance of contralaterally directed movements of the head and body. Subsequent histological reconstruction of the injection sites indicated that such movements could be obtained from widespread areas within the superior colliculus, including not only lateral stratum album intermediale but also the deep layers, and parts of the medial superficial and intermediate layers. Moreover, sites in or close to lateral stratum album intermediate often gave circling movements with downward pointing head, whereas some sites outside lateral stratum album intermediale gave sustained immobility with the head pointing contralaterally and upwards. This evidence supports the view that tectal efferent pathways besides the tecto-reticulo-spinal pathway are involved in the control of head movement. In addition, at least some of these pathways are not collaterals of the tecto-reticulo-spinal pathway, since the movements were obtained from collicular regions with few tecto-reticulo-spinal pathway cells. Finally, the results are consistent with the view that different collicular output pathways mediate movements that have different functions.

Animals↗

Responses resembling defensive behaviour produced by microinjection of glutamate into superior colliculus of rats.

Electrical stimulation of the superior colliculus in rats elicits not only orienting movements, as it does in other mammals, but also behaviours resembling such natural defensive responses as prolonged freezing, cringing, shying, and fast running and jumping. To investigate the location of the cells mediating these behaviours, the superior colliculus was systematically mapped with microinjections of sodium L-glutamate (50 mM, 200 nl), and the resultant behavioural changes as assessed in an open field were analysed for defence-like responses. The main regions that gave defensive behaviour were (i) rostromedial superior colliculus (all layers), and (ii) both medial and lateral parts of the caudal deep layers. Cells in these areas project into the ipsilateral descending pathway. However, the cells of origin of this pathway are also found in collicular regions, such as rostral intermediate gray and parts of far caudal colliculus, that did not give defensive movements in response to glutamate stimulation. It is unclear whether this is because only parts of the ipsilateral pathway mediate defensive behaviours, or because glutamate is a relatively inefficient stimulating agent for these systems. An unexpected feature of the results was that at a number of collicular sites the nature of the defensive response changed with successive (up to three) injections of glutamate, often appearing to become more intense. Whether the mechanism underlying this potentiation is related to the conditioning of natural defensive behaviour is unknown.

Animals↗

Cardiovascular and respiratory changes elicited by stimulation of rat superior colliculus.

Stimulation of the rat superior colliculus can produce either orienting or defensive movements, which if elicited by natural stimuli would be accompanied by cardiovascular changes. To assess whether cardiovascular changes might also be mediated by the superior colliculus, blood pressure and heart rate were measured in Saffan-anaesthetised rats while the dorsal midbrain was systematically explored with electrical and chemical stimulation. Electrical stimulation (10 sec trains of 0.3 msec 100 Hz cathodal pulses, 50 microA) within the superficial and intermediate layers of the rostral superior colliculus transiently lowered blood pressure without affecting heart rate. In contrast sites within the deep layers, and in adjacent periaqueductal grey and midbrain tegmentum, gave pressor responses accompanied by a variety of heart-rate changes, that usually included a period of bradycardia. A roughly similar distribution was obtained with the cell-stimulant bicuculline (200 or 500 nl, 490 microM), though sodium L-glutamate (200 nl, 0.05 or 1.0 M) was ineffective. These results suggest that (a) cardiovascular responses can be produced by stimulation of the rat superior colliculus; (b) their nature depends on the location of the stimulation; and (c) they may be mediated in part by cells differentially sensitive to glutamate and to bicuculline. In addition, in some animals respiratory responses were measured stethographically. Short-latency increases in thoracic girth, often accompanied by increases in respiratory rate and depth, were elicited by electrical stimulation from 61% of the collicular sites examined, and by microinjection of glutamate from 56% of collicular sites. These data suggest that (a) cells within the superior colliculus are capable of influencing respiration; (b) given the widespread distribution of responsive sites within the superior colliculus, the respiratory changes may be preparatory for both approach and defensive movements; (c) the collicular cells that affect respiration may be different from those that influence blood pressure, because the latter are relatively insensitive to microinjection of glutamate.

Animals↗

Morphologic features of rejection in long-surviving canine small bowel transplants.

We studied morphologic features of small bowel transplants in 25 dogs immunosuppressed by cyclosporine, and preoperative graft irradiation. Graft and host bowel were compared with respect to multiple histologic parameters in a blinded analysis. A lymphoplasmacytic infiltrate in nerves and vessels in submucosa and muscle was present in 18 graft bowels and only 3 host bowels, suggesting that these findings represent a cellular rejection reaction. The other histologic parameters were the same in graft and host bowel. Although the dogs did not exhibit clinical signs of rejection, end-stage scarring of the bowel and death occurred in 6 dogs. The animals did not develop systemic graft-verus-host reaction. These findings indicate that under cyclosporine therapy, a subclinical rejection reaction persists deep in the wall and may remain undetectable in mucosal biopsies, but may progress to destroy the graft.

Animals↗

Thyroid metastases from renal carcinoma.

The identification and diagnosis of thyroid metastases from renal adenocarcinoma are rare in living patients, though more frequent during autopsy. A case is reported in which the identification of thyroid metastases indicated a clear-cell renal carcinoma in a kidney treated 12 years earlier for emptying of multiple cysts.

Carcinoma, Renal Cell↗

Male hypogonadism of uremic patients on hemodialysis.

Primary hypogonadism occurring among uremic men on hemodialysis has been widely investigated, yet few data are available concerning the general pattern of steroidogenesis. In 161 hemodialysis patients and in 83 healthy subjects, serum levels of gonadotropins (LH and FSH), prolactin (PRL), testosterone (T), androstenedione (A), estrone (E1), estradiol (E2), and dehydroepiandrosterone-sulphate (DHEA-S) were assessed through RIA methods. Mean +/- SD hormone levels were: LH 45.6 +/- 41.1 mIU/ml, FSH 16.3 +/- 16 mIU/ml, PRL 42.4 +/- 69.1 ng/ml, A 0.83 +/- 0.27 ng/ml, E1 64.3 +/- 31.7 pg/ml, all higher than controls; T 289 +/- 125 ng/100 ml, E2 11.8 +/- 3 pg/ml, and DHEA-S 1.4 +/- 1.4 micrograms/ml, all lower than controls. The A/T and E1/E2 ratios were also higher than controls and showed a good positive linear correlation (r = 0.40; p less than 0.001) between each other. The uremic damage acts at the testis level, impairing the activity of the enzyme 17-beta-hydroxysteroid-dehydrogenase (17-OHSD), even if a derangement of the peripheral interconversion between steroids cannot be excluded.

Adult↗

Effect of pretransplant graft irradiation on canine intestinal transplantation.

This study was done to define the tolerance of ex vivo administered irradiation to intestinal allograft and to assess the effect of irradiation on the incidence and severity of rejection and graft versus host disease after intestinal transplantation in dogs. Excessive intestinal damage was produced by 2,500 rads, but 750 and 1,500 rads produced no detectable acute or chronic damage in dogs observed from 100 days to two years. Using cyclosporine for postoperative immunosuppression, 1,500 rads reduced the incidence of acute (p = 0.05) and chronic rejection (p = 0.08), yet did not impair intestinal absorption of cyclosporine. The greatest improvement in survival occurred with 750 rads (p = 0.02). Histologic evidence of graft versus host disease appeared in the native small intestine in two of four long term surviving dogs receiving a nonirradiated graft but in none of the dogs receiving irradiated grafts. Irradiation of the graft may be a promising adjunct in the search for a clinically applicable method of intestinal transplantation.

Animals↗

Further evidence for segregated output channels from superior colliculus in rat: ipsilateral tecto-pontine and tecto-cuneiform projections have different cells of origin.

Two of the targets of the ipsilateral descending pathway from the superior colliculus are the cuneiform area (immediately ventral to the inferior colliculus), and the dorsolateral basilar pons. The cells of origin of the projections to these targets in rat were studied with a retrograde double-labelling technique, using the fluorescent tracers True blue and Diamidino yellow. Although many tectal cells were single-labelled by injections into basilar pons or the cuneiform area, less than 5% were double-labelled. The two projections thus appear to arise mainly from separate populations of cells within the superior colliculus.

Animals↗

The limitation of liver function tests in metastatic carcinoid tumors.

To evaluate the utility of liver function tests (LFT) as indicators of metastatic carcinoid tumors, a retrospective study was performed. The LFT results of 17 patients with carcinoid tumors metastatic to the liver were compared with 17 patients with other malignant tumors. In the noncarcinoid group, 82.4% of the patients had elevated alkaline phosphatase (AP) or gamma glutamyl transpeptidase (GGTP), whereas only 28.6% of carcinoid patients had abnormal enzymes. The medians of all LFT values were significantly higher in noncarcinoid patients than in the carcinoid group, except for glutamic pyruvic transaminase (SGPT). Our data indicate that LFT are helpful in screening for liver metastases in patients with noncarcinoid tumors, but are unreliable in carcinoid tumors. Imaging tests should be used to rule out liver metastases in carcinoid tumors, irrespective of LFT results.

Carcinoid Tumor↗