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Biomedical subjects

H P Smith

Publications and source records attributed to H P Smith.

At least 19 recordsLinked to original sources
PubMed1997

Locomotor inhibition, yawning and vacuous chewing induced by a novel dopamine D2 post-synaptic receptor agonist.

The N-n-propyl analog of dihydrexidine ((+/-)-trans-10, 11-dihydroxy-5,6,6a,7,8,12b-hexahydrobenzo[a]phenanthridine) is a dopamine receptor agonist with high affinity for dopamine D2 and D3 receptors (K0.5 = 26 and 5 nM, respectively). Members of the hexahydrobenzo[a]phenanthridine structural class are atypical because they display high intrinsic activity at post-synaptic dopamine D2 receptors, but low intrinsic activity at dopamine D2 autoreceptors. The present study examined the effects of (+/-)-N-n-propyl-dihydrexidine on unconditioned behaviors in rats. The most striking results observed were large, dose-dependent decreases in locomotor activity (e.g., locomotor inhibition), and increases in vacuous chewing; yawning was also increased at the highest dose of (+/-)-N-n-propyl-dihydrexidine. The locomotor inhibition and yawning induced by (+/-)-N-n-propyl-dihydrexidine were blocked by pre-treatment with (-)-remoxipride (S(-)-3-bromo-N-((1-ethyl-2-pyrrolidinyl)-methyl)-2, 6-dimethoxybenzamide), a dopamine D2 receptor antagonist, but not by the dopamine D1 receptor antagonist (+)-SCH23390 (R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1 H-3-benzazepine). Vacuous chewing was decreased by both (-)-remoxipride and (+)-SCH23390. These data support the hypothesis that a subpopulation of post-synaptic dopamine D2 receptors has a critical role in decreases in locomotor activity and induction of vacuous chewing and yawning.

Adrenergic alpha-2 Receptor Antagonists↗
PubMed1995

Laparoscopic and thoracoscopic assistance with CSF shunts in children.

Between June 1992 and June 1994, six children underwent laparoscopic or thoracoscopic assistance in the management of cerebrospinal fluid (CSF) shunts. Four children (3 to 12 years of age) required laparoscopic assistance. Two children (5 and 10 years of age) underwent thoracoscopy with insertion of syringopleural shunts for decompression of cervicothoracic hydromyelia. Most children who require CSF decompression do not need endoscopic assistance for placement of the terminal portion of the shunt. However, in selected patients who have undergone previous abdominal procedures, in patients with a persistent pseudocyst occupying an extensive portion of the abdominal cavity, and in patients requiring removal of a disconnected shunt, laparoscopy is the ideal approach. Thoracoscopy for a syringopleural shunt prevents the need for minithoracotomy.

Cerebrospinal Fluid Shunts↗
PubMed1993

Influence of the T cell receptor alpha-chain on T cell reactivity and tolerance to Mls-1 in T cell receptor beta-chain transgenic mice.

Previous analyses of a TCR V beta 8.1 transgenic mouse revealed multiple mechanisms of tolerance to the retroviral superantigen, Mls-1. Whereas some T cells were clonally deleted in the thymus, others became anergic in the periphery, or remained unaffected by the expression of Mls-1. In addition, a strong correlation between TCR alpha-chain usage and Mls-1 reactivity of individual transgenic V beta 8.1+ T cell hybridomas was established. Based on these observations, we speculated that the different mechanisms of tolerance were a consequence of the alpha-chain-mediated differences in Mls-1 reactivity. In the current studies, we make use of a V alpha 2-specific mAb to directly examine the role of the alpha-chain on tolerance in this transgenic model. We show, first, that V alpha 2+ CD4+ T cells, as a group, are relatively less Mls-1-reactive, and are elevated twofold in the periphery of Mls-1+ compared with Mls-1-V beta 8.1 transgenic mice. This elevated expression is also seen in the V alpha 2+ CD4+ population of mature thymocytes, but not in immature thymocytes. Second, Mls-1-induced neonatal tolerance in Mls-1-negative mice caused an increase of V alpha 2+ CD4+ T cells, comparable with the frequency of expression in transgenic mice that endogenously expressed Mls-1. Third, we have demonstrated a general correlation between the age-dependent increase in Mls-1-expression and the levels of V alpha 2+ CD4+ T cells during the first 4 wk of life. Taken together, these data suggest that the over-expression of V alpha 2+ CD4+ T cells in Mls-1+ mice is a consequence of mechanisms of tolerance, predominantly mediated by preferential lack of clonal deletion in the thymus. These data support the idea that clonal deletion is a competitive process and the influence of the TCR alpha-chain on the strength of Mls-1 reactivity of individual V beta 8.1+ transgenic T cells controls their susceptibility to clonal deletion.

Animals↗
PubMed1993

Major histocompatibility complex-specific recognition of Mls-1 is mediated by multiple elements of the T cell receptor.

We have recently shown that recognition of the mouse mammary tumor virus 9-associated superantigen (vSAG-9) by murine V beta 17+ T cells is strongly influenced by the major histocompatibility complex (MHC) class II haplotype of the presenting cells, resulting in a form of MHC-restricted recognition. This finding was unexpected, because T cell recognition of another well-characterized retroviral superantigen, minor lymphocyte-stimulating antigen 1 (Mls-1), had been shown to be independent of the MHC haplotype of the presenting cell. To determine whether recognition of vSAG-9 and Mls-1 is fundamentally different, we undertook an extensive analysis of MHC haplotype influences on vSAG-9 and Mls-1 recognition by panels of T cell hybridomas. Our results show that, although most hybridomas recognized Mls-1 regardless of the MHC haplotype of the presenting cells, as previously described by others, some hybridomas exhibited unique patterns of MHC fine specificity. Thus, T cell recognition of vSAG-9 and Mls-1 is not fundamentally different, but the apparent differences can be explained in terms of frequency. The MHC fine specificity of individual Mls-1-reactive hybridomas was influenced by both V beta and non-V beta T cell receptor (TCR) elements. First, the influence of the V beta element was apparent from the observation that V beta 8.2+ hybridomas were significantly more MHC specific in their recognition of Mls-1 than V beta 8.1 hybridomas. Second, a role for the TCR alpha chain was implicated from the distinct patterns of fine specificity of Mls-1 reactivity among a panel of transgenic hybridomas that expressed an identical beta chain (V beta 8.1D beta 2J beta 2.3C beta 2). Sequence analysis revealed that junctional residues of the TCR alpha chain and/or V alpha/J alpha combinations influenced the MHC haplotype fine specificity for Mls-1. Third, D beta J beta influences were implicated, in that the transgenic hybridomas expressed distinctive patterns of Mls-1 fine specificity not represented among V beta 8.1+ nontransgenic hybridomas. The findings that T cell recognition of endogenous superantigen is MHC specific, and that this specificity correlates with non-V beta elements of the TCR, support the hypothesis that there is a direct interaction between the TCR and either polymorphic residues of the MHC class II molecule or haplotype-specific dominant peptides presented by class II.

Animals↗
PubMed1992

T cell receptor alpha-chain influences reactivity to Mls-1 in V beta 8.1 transgenic mice.

Most, but not all, V beta 8.1+ T cells respond to M1s-1 and are clonally deleted in the thymus of M1s-1-expressing animals. To formally examine the role of the TCR alpha-chain in reactivity and tolerance to M1s-1, we have analyzed M1s-1 reactivity in a large panel of CD4+ hybridomas generated from TCR V beta 8.1 transgenic mice, that express an identical, potentially M1s-1-reactive beta-chain. The data show that the alpha-chain strongly influences the M1s-1 reactivity of the hybridomas and that the differences in reactivity had relevance for tolerance. Thus, V alpha 11+ hybridiomas were biased toward M1s-1 reactivity and V alpha 11+ T cells were correspondingly absent from the peripheral repertoire of M1s-1-expressing transgenic mice. V alpha 2+ hybridomas, on the other hand, were biased against M1s-1 reactivity, and V alpha 2+ T cells were correspondingly amplified in the M1s-1-expressing transgenic mice. Structural analysis of the alpha-chains revealed that the M1s-1 reactivity of the V alpha 11+ hybridomas segregated precisely with family member, such that V alpha 11.1+ hybridomas were M1s-1-reactive and V alpha 11.3+ hybridomas were not M1s-1-reactive. On the other hand, there was not a clear correlation between family member and M1s-1 reactivity in the V alpha 2+ hybridomas. The hybridomas also showed striking variation in their reactivity to staphylococcal enterotoxin B (SEB), and the SEB reactivity of the V alpha 11+ hybridomas correlated precisely with family member and with M1s-1 reactivity. In contrast, there was not a clear correlation with V alpha 2+ alpha-chain structure and SEB reactivity. Also, there was no correlation between M1s-1 reactivity and SEB reactivity in individual V alpha 2+ hybridomas, suggesting that the recognition of the two superantigens by the same TCR is not equivalent. Taken together, these data define a role for the TCR alpha-chain in superantigen reactivity and T cell tolerance, and provide a structural explanation for the different fates of M1s-1-reactive T cells in normal and transgenic mice.

Amino Acid Sequence↗
PubMed1987

The surgical treatment of skull-base tumors with intracranial extension.

As a discipline, skull-base surgery via the transtemporal route has matured since 1975. Previously considered unresectable, skull-base tumors with intracranial extension can now be successfully removed by means of modification of contemporary exposures with neurosurgical collaboration. Between September 1970 and February 1986, 126 skull-base tumors have been operated on by The Otology Group, P.C. Of these, 49 had intracranial extension. In this article, techniques for tumor removal and dural defect reconstruction are outlined. A single-staged procedure is advised. The advantages of and exceptions to this format are described. Techniques that will prevent postoperative cerebrospinal fluid leakage are highlighted. Results and complications of this surgical series are discussed, and team aspects of this surgery are emphasized.

Adolescent↗
PubMed1987

Management of orbital-cranial trauma.

Orbital-cranial injuries have the greatest potential for death and disability of any condition treated by the ophthalmologist. An object that penetrates through the orbit into the brain may leave only a small entrance wound. Patients can have normal vision, neurologic exam, and plain x-rays despite trauma that may lead to meningitis, brain abscess, or pneumocephalus. The CT scan greatly aids in both the early and late management of blunt and penetrating orbital-cranial trauma. The detection of pneumocephalus may be the only clue that intracranial penetration has occurred. Blunt trauma can cause vision loss, ophthalmoplegia, ptosis, and intracranial injury. Management of orbital-cranial trauma frequently requires a team approach by the ophthalmologist and neurosurgeon due to the complexity of these injuries.

Brain Injuries↗
PubMed1986

Cerebellopontine angle lipomas.

Lipomas of the intracranial vault are uncommon lesions. Rarely, lipomas of the cerebellopontine angle have been identified. The two cases of cerebellopontine angle lipomas reported herein brings the number of recorded cases to 13.

Brain Stem↗
PubMed1986

Patient positioning and nasal intubation for carotid endarterectomy.

Exposure of a very rostral carotid bifurcation for endarterectomy may occasionally be difficult. We are reporting a simple yet effective way to gain several centimetres of exposure of the distal cervical portion of the internal carotid artery in this circumstance.

Carotid Arteries↗
PubMed1986

Comparison of mannitol regimens in patients with severe head injury undergoing intracranial monitoring.

Eighty patients sustaining head injuries and presenting with Glasgow Coma Scale scores of 8 or less were entered into a prospective randomized study to assess the benefit of intracranial pressure (ICP) monitoring with two regimens of mannitol administration. Group I was treated with mannitol for ICP elevations greater than 25 mm Hg, while Group II received empirical mannitol therapy irrespective of ICP readings. No statistically significant differences in mortality rate or neurological outcome were demonstrated between the two groups. These results are comparable to those of several published series of head-injured patients receiving similar treatment from 1977 to 1982. However, those series must be reassessed in light of recently published studies with treatment initiated at lower levels of ICP.

Adolescent↗
PubMed1983

Subdural empyema and epidural abscess in children.

From January 1, 1954, through December 31, 1981, 31 children were treated at The Hospital for Sick Children in Toronto, Ontario, for subdural empyema (22 cases), epidural abscess (6 cases), and infected nidi at both subdural and epidural sites (3 cases). All but four of the children with subdural empyema were from 6 months to 2 years of age or from 12 years to 16 years of age; all children with epidural abscess fitted into the older age group. The subdural empyemas developed from varied sources, but the paranasal sinuses, the ears, and the mastoids processes were predominantly affected. Five subdural empyemas developed following craniotomy or shunt procedures. The epidural abscesses developed mostly from infections in the paranasal sinuses and the middle ears. Two of the combined infections developed from the paranasal sinuses; the third followed craniotomy. The infecting bacteria varied, but were usually Streptococci and were common to both the subdural and epidural sites. The subdural empyemas presented as focal seizures in the older group, and that group of patients was more seriously ill and had greater focal deficit; the mortality rate was 13%. Epidural abscesses only rarely presented with focal deficit, and diagnosis was delayed in most instances; no deaths occurred in this group. Two cases are reported in detail to illustrate the principles and pitfalls of surgical management of these intracranial infections in the pediatric age group.

Adolescent↗
PubMed1981

Oculomotor palsy with pupillary sparing, coincidental aneurysm, and chronic lymphocytic leukemic meningeal infiltration.

A patient with oculomotor palsy with pupillary sparing was shown angiographically to have an aneurysm of the internal carotid artery, which proved at operation to arise distal to the origin of the ophthalmic artery. It did not impinge on the oculomotor nerve at any point. The oculomotor palsy persisted postoperatively, and complete intrinsic and extrinsic ophthalmoplegia developed. Cytological studies of cerebrospinal fluid were then made and were positive for malignant lymphocytic leukemic cells. Despite the fact that an aneurysm causing oculomotor palsy with pupillary sparing has been reported, we recommend that nonaneurysmal causes be considered first in patients presenting with that neurological sign.

Aged↗
PubMed1981

Biological features of meningiomas that determine the production of cerebral edema.

Although meningiomas are known to cause varying degrees of cerebral edema, the relative importance of their location, size, histological subtype, and other histological features in the production of cerebral edema has not been studied adequately. Therefore, we undertook a retrospective analysis of 43 meningiomas excised between 1975 and 1980. The results indicate that histological subtype has no relationship to the production of cerebral edema, with one exception. Meningiomas containing partly or completely a hemangiopericytic component were the only histological subtype associated consistently with cerebral edema. The location of a meningioma per se may not determine the production of cerebral edema. A relationship between size, aggressive histological features, vascular proliferative changes, and the production of cerebral edema was seen. The need for and the nature of further studies required to explain the cerebral edema that may be associated with small meningiomas are discussed.

Brain Edema↗
PubMed1981

Radiofrequency neurolysis in a clinical model. Neuropathological correlation.

Reports differ on which nerve fibers are affected by radiofrequency lesions made in peripheral nerves, some stating that primarily the myelinated delta and unmyelinated C fibers are destroyed, others stating that the destruction affects all sizes of nerve fibers and both myelinated and unmyelinated fibers. This study was designed to confirm one of those two findings, and to study the role that different temperatures might play in determining which fibers are affected. Radiofrequency lesions (85 degrees C for 2 minutes) were made in dogs by placing a temperature-monitored electrode into the lumber intervertebral foramina. The dogs were killed at intervals up to 6 weeks after rhizotomy, and the lesions were studied by light and electron microscopy. In all lesions, there was a total loss of unmyelinated fibers and a nearly total loss of myelinated fibers. In other dogs, 2-minute lesions were made at 45 degrees, 55 degrees, 65 degrees, and 75 degrees C, and the lesions examined 1 week later. Again, all sizes and all types of fibers were destroyed.

Animals↗
PubMed1980

Anterior sacral meningocele: two case reports and discussion of surgical approach.

Virtually all patients with anterior sacral meningocele have a pelvic mass with symptoms and signs relating to pressure of the mass on adjacent structures. Constipation is a universal complaint; urinary incontinence is common. A headache often develoips when the patient stands, due to lowered spinal fluid pressure as the meningocele sac fills. A scimitar-shaped sacrum on anterioposterior plain roentgenograms of the spine is pathognomonic. The coccyx may be absent, and the lower sacral laminate may be absent or incomplete. Myelography confirms the diagnosis and should be done with large volumes of iophendylate in order to fill the sac. Only approximately 130 anterior sacral meningoceles have been reported in the literature. This article presents 2 more cases, both seen at the North Carolina Baptist Hospital. The surgical approach to both was through a sacral laminectomy; the communicating stalk was ligated and the meningocele was removed. One patient was 11 years old and had a large suprapubic pelvic mass found on routine examination. She is neurologically normal postoperatively. The other was 7 years old and had had fecal incontinence since birth. That incontinence is less severe postoperatively and the patient is neurologaically normal.

Child↗
PubMed1980

Odontoid compression of the brain stem in a patient with rheumatoid arthritis. Case report.

Cervical spine involvement by rheumatoid arthritis is common; brain-stem compression secondary to vertical subluxation of the odontoid in patients with rheumatoid arthritis is rare. Vertical subluxation results from 1) destruction of the transverse atlantal, apical, and alar ligaments of the atlas and odontoid, and 2) bone resorption in the occipital condyles, lateral masses of the atlas, and basilar processes of the skull. Neurological symptoms result from direct compression of the brain stem or from ischemia secondary to compression of vertebral arteries, anterior spinal arteries, or small perforating arteries of the brain stem and spinal cord. A case is reported in which a slowly progressive neurological deficit developed in a woman with rheumatoid arthritis following a fall from a stretcher. Neruological symptoms represented direct compression of the medulla by the dens, a mechanism confirmed at operation and autopsy. Recognition of progressive neurological deficit is often difficult in patients with rheumatoid arthritis because of their inactivity and their atrophic and immobile joints, but is essential if appropriate decompressive or stabilizing procedures are to be done. In patients with vertical subluxation of the dens, the transoral approach with removal of the odontoid is recommended. Decompression should be extensive, including the fibrous capsule around the odontoid and overlying synovial tissue as well as the odontoid itself.

Arthritis, Rheumatoid↗