Swimming with dolphins.
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Journal Article↗
Biomedical subjects
J Ogilvie
Publications and source records attributed to J Ogilvie.
Imidazoline I(2)-receptors and spinal reflexes in the decerebrated rabbit.
Idazoxan potentiates spinal reflexes in the decerebrated rabbit, an effect that has been attributed to antagonism of tonic noradrenergic inhibition. It is now known that this drug has a higher affinity for I(2)-imidazoline receptors than alpha(2)-receptors. The roles of I(2)-receptors in modulating transmission in spinal reflex pathways have been investigated using the selective ligands RX 821029 and RS-45041-190, and, as I(2)-receptors are closely associated with monoamine oxidase (MAO), the MAO inhibitors pargyline and clorgyline. In decerebrated rabbits with an intact spinal cord, intrathecal doses of 5-365 microg (cumulative) of the I(2)-ligands augmented, to 150-180% of pre-drug levels, the reflex responses of medial gastrocnemius motoneurones to electrical stimulation of the sural nerve, and significantly increased mean arterial blood pressure by approximately 10 mmHg over pre-drug values. Neither MAO inhibitor had significant effects on reflexes, but the highest dose of the MAO-A selective agent clorgyline (365 microg cumulative) caused a significant rise in blood pressure of 6 mmHg. Neither the I(2)-ligands nor the MAO inhibitors prevented the further enhancement of reflexes or blood pressure by subsequent administration of the selective alpha(2)-adrenoceptor antagonist RX 821002. In decerebrated, spinalized rabbits, intrathecal RS-45041-190 (60 microg, single dose) increased spinal reflex responses to 109% of pre-drug values, a significantly smaller effect than that seen in non-spinal preparations, and had no effect on blood pressure. These data show that imidazoline I(2)-receptors can influence somatic and autonomic motor outflows. These effects should be taken into account when interpreting the spinal effects of imidazoline-based adrenoceptor-active drugs.
Adrenergic alpha-Antagonists↗
The involvement of tachykinin NK2 and NK3 receptors in central sensitization of a spinal withdrawal reflex in the decerebrated, spinalized rabbit.
Repetitive electrical stimulation of the sural nerve at a strength sufficient to excite C-fibres results in prolonged (> 20 min) increases in the reflex responses of gastrocnemius motoneurones evoked by stimulation of myelinated axons in the sural nerve. We have tested the susceptibility of this effect to blockade of tachykinin NK2 and NK1 receptors. In the control state, iterative stimulation of sural nerve C fibres increased gastrocnemius reflexes to a peak of between 200 and 400% of pre-stimulus levels, an effect that recovered to baseline values over 23-30 min. Pre-treatment with selective antagonists for NK2 (SR 48968, 1 mg/kg i.v.) or NK3 (SR 142801, 0.1 and 1 mg/kg i.v.) receptors failed to alter the peak facilitation resulting from sural nerve stimulation. However, both drugs significantly reduced the duration of enhancement of reflexes, to 18 min after SR 48968 and to 5 min after SR 142801. The inactive enantiomers of these compounds (SR 48965 and SR 142806, both 1 mg/kg i.v.) did not reduce facilitation of reflexes after sural nerve stimulation. We conclude that activation of tachykinin NK3 receptors is a major factor in maintaining central sensitization of the sural-gastrocnemius reflex after electrical stimulation of sural nerve C-fibres. The effects of SR 48968 were surprisingly weak and may have resulted from an effect of this compound at NK3 receptors.
Animals↗
Never forget a faceellipsis?
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Journal Article↗
Tonic adrenergic and serotonergic inhibition of a withdrawal reflex in rabbits subjected to different levels of surgical preparation.
The excitability of the heel-gastrocnemius withdrawal reflex pathway has been monitored in rabbits undergoing surgical preparation for electrophysiological experimentation under Saffan anaesthesia. Reflexes were evoked by percutaneous electrodes inserted at the heel and recorded as electromyograph signals from the ipsilateral medial gastrocnemius muscle. Two levels of surgery were carried out. The "full surgical" preparation was performed under deep Saffan anaesthesia. The trachea, carotid artery, jugular vein and intrathecal space (via a small laminectomy at L1) were cannulated, the animals were decerebrated by suction, and the left hindlimb was immobilized by screw clamps applied to the tibia and the femur. The sciatic nerve and its branches were exposed by bisection of the posterior biceps muscle and the anaesthetic was withdrawn. In the "reduced surgery" preparation, procedures were carried out with a lighter level of Saffan anaesthesia and operated tissues were infiltrated with local anaesthetic. Only the cannulations were performed in these animals. The excitability of the heel-gastrocnemius reflex declined throughout the full surgical preparation, with the median threshold increasing from 0.8 to 4.2 mA (n=19) and responses to suprathreshold stimuli reducing in size. Most of this effect was reversed after surgery was complete and anaesthesia withdrawn subsequent to decerebration. There were no significant changes in reflex excitability during the reduced surgery preparation (n = 15). Animals prepared by each of these protocols were given increasing intrathecal doses of either the selective alpha2-adrenoceptor antagonist RX 821002 (0.3 to 300 microg) or the serotonin/5-hydroxytryptamine (5-HT)1A-receptor antagonist WAY-100635 (0.01 to 30 microg). Both drugs caused significant, dose-dependent increases in reflex responses, to four to six times pre-drug control in both groups of animals. There were no differences in the effects on reflexes of either drug between the preparations. Thus, surgical preparation of decerebrated rabbits for electrophysiological recording results in depression of hindlimb withdrawal reflexes, although much of this effect did not persist beyond the completion of surgery. Tonic monoaminergic inhibition of reflexes was present to the same extent in both preparations investigated and is not therefore an epiphenomenon of the way in which the animals were prepared.
Adrenergic alpha-Antagonists↗
Differences in opioidergic inhibition of spinal reflexes and Fos expression evoked by mechanical and chemical noxious stimuli in the decerebrated rabbit.
Noxious mechanical and chemical stimuli were applied to the toes of the left hind limb of decerebrated, spinalized rabbits and their effects on a hind limb spinal withdrawal reflex and expression of Fos-like immunoreactivity in the spinal cord were measured. The animals were prepared so as to minimize nociceptive inputs arising from surgery. A single crush stimulus applied with a pair of haemostatic forceps caused long-lasting (c. 20 min) inhibition of reflexes evoked in medial gastrocnemius motoneurons by electrical stimulation of the skin at the heel. Naloxone (0.25 mg/kg i.v.) increased reflexes to more than 1000% of pre-drug controls and reversed crush-evoked inhibition. Mustard oil applied to the toes had no consistent effects on the heel-gastrocnemius reflex before or after naloxone. Both crush and mustard oil stimuli gave rise to unilateral increases in the number of Fos-immunopositive profiles in the superficial dorsal horn of spinal segments L7 and S1. There were significantly more Fos-immunoreactive elements in the central and lateral parts of lamina I of both segments in animals receiving the crush stimulus than there were in animals receiving the mustard oil stimulus. Immunochemical localization of enkephalins in rabbit spinal cord showed a dense network of fibres and terminals in laminae I and II, accompanied by infrequent but distinctly stained neuronal cell bodies. The same pattern, with increased numbers of visible cell bodies, was seen after treatment with colchicine. The present data show that tonic and stimulus-evoked opioidergic inhibition of the heel-gastrocnemius reflex of the rabbit are not epiphenomena of surgical preparation of the hindlimb. Opioid-mediated inhibition of the heel-gastrocnemius withdrawal reflex of the rabbit was evoked by noxious mechanical but not by chemical stimulation of the toes. Of these stimuli, the former gave rise to greater activation of neurons in central and lateral lamina I of segments L7 and S1, the region of termination of afferent fibres from the heel and the location of some enkephalin-positive neuronal cell bodies. Thus, noxious mechanical stimulation of the toes elicits inhibition of the heel-gastrocnemius withdrawal reflex, probably via activation of enkephalinergic neurons in the lateral half of lamina I in the L7 and S1 segments.
Animals↗
On the role of 5-HT1B/1D receptors in modulating transmission in a spinal reflex pathway in the decerebrated rabbit.
1. In decerebrated rabbits, the selective 5-HT1B/1D receptor antagonist GR 127,935 had no significant effects on reflexes evoked in medial gastrocnemius motoneurones by electrical stimulation of the sural nerve, or on arterial blood pressure or heart rate when given by the intrathecal (up to 543 nmol cumulative) or intravenous (up to 1.8 micromol cumulative) routes. 2. In decerebrated, spinalized rabbits, intrathecal GR 127,935 in doses of up to 543 nmol, had no effect on the sural-gastrocnemius reflex. Furthermore, this drug failed to alter enhancement of the sural-gastrocnemius reflex induced by 8-hydroxy-2-(di-n-propyl)aminotetralin (8-OH-DPAT), given at 300 nmol kg-1 i.v. 3. In decerebrated, spinalized rabbits, the selective 5-HT1B/1D receptor agonists L-694,247 (cumulative doses of 2 - 243 nmol kg-1 i.v.) and L-741,604 (cumulative doses of 3 - 307 nmol kg-1 i.v.), each caused the sural-gastrocnemius reflex to increase to 140% of pre-drug levels, and arterial blood pressure to rise by about 10 mmHg. Subsequent administration of GR 127,935 at 0.9 - 1.8 micromol kg-1 reversed the pressor effect of the agonists but not the increase in reflexes. The 5-HT1A receptor antagonist WAY-100,635 (185 nmol kg-1 i.v.) also failed to reverse the increase in reflexes, but the 5-HT1B/1D/5-HT2/5-HT7 ligand ritanserin (1.6 micromol kg-1 i.v.) restored reflexes to pre-drug control values after L-741,604 (it was not tested against L-694,247). 4. These data indicate that 5-HT1B/1D receptors do not significantly modulate transmission in the sural-gastrocnemius reflex pathway, and that the enhancement of reflexes by 8-OH-DPAT and L-741,604 is probably mediated by 5-HT7 receptors.
8-Hydroxy-2-(di-n-propylamino)tetralin↗
Effect of RX 821002 at 5-HT1A-receptors in rabbit spinal cord in vivo.
1. The activity of RX 821002 (2-methoxy idazoxan) at 5-HT1A-receptors in the spinal cord has been investigated in decerebrated, spinalized rabbits. Reflexes evoked in medial gastrocnemius motoneurones by electrical stimulation of the sural nerve were unaffected by intrathecal (i.th.) administration of RX 821002 (111 and 664 nmol cumulative, n = 7), although the highest dose of this drug did produce a significant increase in heart rate of 28 +/- 7 beats min(-1). Subsequent administration of the 5-HT1A-receptor agonist (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) at 300 nmol, i.th., facilitated reflexes to a median of 144% of pre-drug controls, an effect that was partially reversed (to a median value of 120% of pre-drug values) by subsequent administration of the 5-HT1A-receptor antagonist WAY-100635, at 185 nmol i.th. 2. In a separate set of experiments, 8-OH-DPAT was given at 30 nmol i.th. and potentiated reflexes to a median of 170% of pre-drug levels (n = 8). Subsequent administration of RX 821002 (at a cumulative dose of 1.11 micromol, i.th., n = 5) significantly reduced gastrocnemius responses to a median of 154% of control values. 3. After a 3 h recovery period, 8-OH-DPAT was re-administered at 30 nmol, i.th., and increased reflexes to a median value of 151% of pre-drug levels, an effect not significantly different from when it was given alone. WAY-100635 dose-dependently antagonized this effect, causing significant reductions in reflexes at a cumulative dose of 0.55 nmol, i.th., and complete reversal of the effects of 8-OH-DPAT at a cumulative dose of 5.5 nmol. 4. These data show that, at intrathecal doses up to 664 nmol, RX 821002 is devoid of agonist activity at 5-HT1A-receptors. It appears to be a very weak antagonist at these sites in vivo, being some 2000 times less potent than WAY-100635. The inability of WAY-100635 to block completely the effects of high doses of 8-OH-DPAT has been noted previously and can be explained by non-selective actions of the agonist. However, it would appear that a 30 nmol i.th. dose of 8-OH-DPAT is selective for 5-HT1A receptors in this preparation.
8-Hydroxy-2-(di-n-propylamino)tetralin↗
Enhancement and depression of spinal reflexes by 8-hydroxy-2-(di-n-propylamino)tetralin in the decerebrated and spinalized rabbit: involvement of 5-HT1A- and non-5-HT1A-receptors.
1. In decerebrated, spinalized and paralyzed rabbits, intravenous administration of the 5-HT1A-receptor agonists (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 3-300 nmol kg(-1), cumulative) and flesinoxan (22-2200 nmol kg(-1), cumulative) significantly increased the short latency reflex evoked in gastrocnemius medialis motoneurones by electrical stimulation of all myelinated afferents (Abeta and Adelta fibres) of the sural nerve. Reflexes increased to median values of 198% (inter-quartile range (IQR) 148-473%) and 296% (IQR 254-522%) of pre-drug values with the highest doses of 8-OH-DPAT and flesinoxan, respectively. The enhancement of reflexes induced by 5-HT1A-receptor agonists was not reversed by the selective 5-HT1A-receptor antagonist (S)WAY-100135 (2.05 micromol kg[-1]). 2. The effects of 8-OH-DPAT were tested after pretreatment with (S)WAY-100135 (2.05 micromol kg[-1]), its more potent analogue WAY-100635 (185 nmol kg[-1]), and the 5-HT2/5-HT1D-/5-HT7-receptor ligand ritanserin (1.67 micromol kg[-1]). 8-OH-DPAT (300 nmol kg(-1) single dose) significantly increased gastrocnemius reflex responses in the presence of (S)WAY-100135 and WAY-100635, to median values of 260% (IQR 171-295%) and 165% (IQR 136-170%) of pre-drug levels, respectively. These values were not significantly different from each other, or from the effects of 8-OH-DPAT given alone. When 8-OH-DPAT was given after ritanserin, reflexes were a median of 102% (IQR 76-148%) of pre-drug values: i.e. there was no significant increase in responses. Neither WAY-100635 nor ritanserin had any effects on reflexes per se. 3. WAY-100635 (185 nmol kg[-1]) and ritanserin (1.67 micromol kg[-1]) were given after 8-OH-DPAT (300 nmol kg[-1]). The agonist increased reflexes to a median value of 184% (IQR 135-289%), after which WAY-100635 significantly reduced responses to 165% (IQR 130-254%) and ritanserin further decreased reflexes to a median of 107% (IQR 100-154%) of pre-drug levels, i.e. not significantly different from controls. 4. Previous studies have shown that reflexes evoked by large myelinated axons tend to be suppressed, rather than enhanced, by 5-HT1A-receptor agonists. When tested against reflexes evoked by stimulation of the sural nerve at strengths between 1.5 and 2.5 times threshold, 8-OH-DPAT (3-300 nmol kg(-1), cumulative) and flesinoxan (22-2200 nmol kg(-1), cumulative) significantly reduced gastrocnemius responses to median values of 36% (IQR 15-75%) and 17% (IQR 12-38%) of pre-drug levels, respectively. This inhibition was fully reversed by (S)WAY-100135 (2.05 micromol kg[-1]). 5. These data show that drugs that are agonists at 5-HT1A-receptors increase polysynaptic spinal reflexes evoked by moderate to high stimulus intensities and depress responses to very low intensity stimuli. The inhibitory effects of these drugs were mediated through 5-HT1A-receptors as they were abolished by a selective antagonist for these sites. However, the facilitatory effects of 8-OH-DPAT could be completely blocked only by a combination of ritanserin, which has no significant affinity for 5-HT1A-receptors, with WAY-100635. It appears that the enhancement of reflexes by 8-OH-DPAT arises from a combined action at 5-HT1A-receptors and other, ritanserin-sensitive, sites which could be 5-HT1D- or 5-HT7-receptors.
8-Hydroxy-2-(di-n-propylamino)tetralin↗
Cytokines in human intraocular inflammation.
The presence of interleukin 6 (IL-6), interleukin 1 (IL-1), interleukin 2 (IL-2) and tumour necrosis factor (TNF) was investigated in vitreous and aqueous aspirates from eyes undergoing vitrectomy for the treatment of different inflammatory conditions. Cadaveric vitreous from 10 normal subjects were used as controls. IL-6 was observed in 5 specimens from eyes with idiopathic uveitis (range = 26-264 pg/ml), in 2 specimens from eyes with uveitis complicated with retinal detachment (28 and 279 pg/ml, respectively), in 6 samples from eyes with diabetic retinopathy (range = 5-480 pg/ml), in one sample from an eye with phacolytic glaucoma (1190 pg/ml) and in one specimen from an eye with Behçet's disease (366 pg/ml). Although IL-1 was detected in 80% of all the samples investigated, concentrations of this cytokine greater than 3 pg/ml were only observed in 2 specimens from eyes with uveitis (5 and 20 pg/ml, respectively) and 2 samples from eyes with diabetic retinopathy (3 and 31 pg/ml, respectively). TNF was present in 3 specimens from eyes with uveitis (range = 2-24 pg/ml) and 1 sample from eyes with diabetic retinopathy (4 pg/ml), but was not detected in the eyes with phacolytic glaucoma or Behçet's disease. IL-2 (less than 0.1 U/ml) was detected in one sample from an eye with uveitis, one specimen from an eye with uveitis complicated with retinal detachment and 2 samples from eyes with diabetic retinopathy. None of the cytokines measured were detected in any of the control vitreous. The present observations suggest that cytokines, particularly IL-6 and IL-1, may act as local amplification signals in pathological processes associated with chronic eye inflammation.
Aqueous Humor↗
The adult diplomyelia syndrome.
Diplomyelia is an uncommon variant of diastematomyelia in which the spinal cord remains divided caudal to the diastematomyelia spur. Presented here are three adults who presented with a sign-and-symptom complex that is likely to occur only when such an anatomic aberration is found. Each patient complained of pain and paresis in one leg. Neurologic examination demonstrated dysfunction of not only both long tracts but also lower motor modalities in the symptomatic leg and no abnormalities in the opposite leg. These findings, therefore, would strongly suggest that each leg was supplied by one of the split spinal cords, with only one cord being compromised. When planning surgical intervention on these patients, one must be aware that removal of the central spur alone may not resolve the problem because the spur, unlike that in diastematomyelia, does not tether the split spinal cords.
Adult↗
Serological biochemical and functional characterisation of three different HLA-DR monoclonal antibodies derived from C57BL6 mice.
C57BL6 mice which do not express I-E gene products were immunised with EBV transformed human B cell lines to generate MoAbs. Three hybridoma supernatants which initially reacted with the immunising donor cell but not a T cell line lacking Class II antigens were further investigated. I-D SDS-PAGE patterns of molecules precipitated by the three supernatants from a cell membrane lysate were characteristic of HLA-Class II alpha and beta chains. Two-dimensional analysis established the specificity of the supernatants as HLA-DR specific. This was confirmed by the reaction patterns with Class II mutant deletant cell lines. In both ELISA and cytotoxicity one reacted with all lymphoblastoid cell lines tested, one reacted with all except two that were DR7 homozygous and the third reacted strongly only with cells that were DR3. All three antibodies were cytotoxic to both peripheral blood lymphocytes and EBV transformed B cell lines. The DR3 specific MoAb (IgG2a) was suitable as a typing reagent. The DR3 reactive MoAb specifically inhibited stimulation by a Dw3 HTC and the other two MoAbs inhibited all HTCs tested. These findings are consistent with the view that certain determinants responsible for the Dw specificities are carried on the DR molecules.
Animals↗
Genu valgum deformity in Hurler syndrome after hematopoietic stem cell transplantation: correction by surgical intervention.
Hematopoietic stem cell transplantation has increased the survival of patients with Hurler syndrome. Genu valgum occurs frequently in untransplanted patients and has been noted in 52% of our patients after stable engraftment. No deformities spontaneously corrected. We describe the orthopaedic management of genu valgum in Hurler syndrome. Medial epiphyseal stapling predictably affects angular deformity in these patients. Recurrence of deformities either after staple dislodgement or surgical removal can occur, and repeated stapling may be required. Surgical epiphyseal stapling has a role in the management of genu valgum in successfully engrafted Hurler patients. We discuss the relationship of this skeletal deformity to other skeletal deformities and alternative therapies for genu valgum.
Adolescent↗
Characterization of two monoclonal antibodies raised against human testicular cells.
Human testicular cells isolated from biopsy tissue were used for generation of monoclonal antibodies. Two hybridoma supernatants C3 and D4 were selected according to their reaction with sperm-precursor cells (immature sperms) in an enzyme-linked immunosorbent assay (ELISA). C3 reacted with testicular but no other tissue. D4 did not reveal any pattern of testicular staining in spite of its similarity to C3 in binding to sperm-precursor cells in ELISA and microcytotoxicity test.
Adult↗
Moving toward collaborative practice on an orthopaedic unit: health care provider involvement in cost containment.
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Cost Control↗
Botulinum toxin: a new therapeutic use.
Botulinum Toxin is a powerful neurotoxin whose therapeutic uses for smooth muscle disorders have received little attention. Through innovative research, gastroenterologists at Johns Hopkins Hospital have developed a simple, less traumatic therapeutic use for this toxin in the treatment of achalasia. In this article, the authors describe the pathophysiology of this disease, its diagnosis and traditional treatment, and the newest potential therapy, Botulinum Toxin (BoTx) injection.
Aged↗