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W B Stewart

Publications and source records attributed to W B Stewart.

At least 37 records · Page 2Linked to original sources

Indomethacin promotes germinal matrix microvessel maturation in the newborn beagle pup.

BACKGROUND AND PURPOSE: Although indomethacin has been demonstrated to prevent germinal matrix and intraventricular hemorrhage in clinical and animal studies, the mechanism of action of this agent to prevent hemorrhage remains unclear. Previous studies have demonstrated both that the microvessels in the germinal matrix of newborn beagle pups undergo basement membrane maturation during the first 4 postnatal days and that indomethacin may promote laminin deposition in tumor cell culture systems. METHODS: We employed the newborn beagle pup model to test the hypothesis that indomethacin may stimulate laminin deposition in germinal matrix microvessels. Newborn pups were randomized to receive either 0.1 mg/kg/dose i.p. indomethacin or an equal volume of saline diluent. Pups received doses of study medication once a day for 1, 2, or 3 days and were studied on postnatal days 1, 2, 3, or 4. Pups were anesthetized and systemically perfused with buffered formalin; the brains were removed and prepared for immunohistochemical study. RESULTS: Sections stained with Bandeiraea lectin demonstrated that there was no difference in germinal matrix vessel density among the postnatal ages studied; similarly, there were no differences in vessel density between saline- and indomethacin-treated animals at any postnatal age. Quantification of germinal matrix stained intensity by confocal microscopy demonstrated significant increases in indomethacin-treated pups for both laminin staining at postnatal days 2 (p = 0.05) and 3 (p = 0.0009) and type V collagen staining at postnatal day 2 (p = 0.011). Although staining for beta 1 integrins increased across postnatal ages, there were no differences between saline- and indomethacin-treated animals. CONCLUSIONS: These data suggest that indomethacin may stimulate basement membrane deposition in the germinal matrix microvessels of newborn beagle pups to prevent germinal matrix and/or intraventricular hemorrhage.

Animals↗

Three dimensional imaging and computer-designed prostheses in the evaluation and management of orbitocranial deformities.

Three dimensional images reconstructed from two dimensional CT scans allow improved analysis of complex orbitocranial bony deformities. This evaluation may be useful in patients with defects resulting from trauma, tumor, congenital abnormalities, or developmental disorders. Diagnosis, surgical management, and long-term follow-up evaluation may be aided by improved understanding of bony contour and volume analysis. Computer designed prostheses can be fabricated to precisely match bony defects and may be used as an alloplastic implant or as a model to aid intraoperative contouring of an autogenous bone graft. The limitations of three dimensional imaging include artifacts in the reconstructed images, increased radiation exposure, and increased cost. The technology is still evolving and the indications and benefits remain undefined at the present time.

Adolescent↗

Orbital exenteration. The reconstructive ladder.

Following orbital exenteration, there is a spectrum of immediate and delayed options for orbital reconstruction. Goals of reconstruction after exenteration include detection of recurrent disease, restoration of boundaries between the orbit and surrounding structures, and optimal aesthetics. Local solutions to problems of the exenterated orbit, such as healing by granulation or application of split-thickness skin grafts, are advantageous for detecting recurrent disease. Regional solutions, involving transfer of periorbital tissue into the orbit, may mask recurrent disease and create adjacent deformity; however, these solutions can be used to restore orbital boundaries and shallow the orbital cavity. Distant solutions, such as skin-muscle flaps and free tissue grafts, allow for facial reconstruction in patients with extensive orbital and periorbital defects.

Adipose Tissue↗

A micro system for rigid bony fixation in orbital surgery.

Plates and screws are effective for rigid internal fixation of bone fractures and osteotomies in the midface, orbit, and cranium. We describe our experience with the Luhr Micro System. This is the newest generation of Luhr Systems and is the smallest system available for rigid internal fixation. The self-tapping screws are 0.8 mm in diameter, with lengths of 2-8 mm. The plates have an extremely flat profile. We have used the Micro System for closure of elective osteotomies following resection of orbital neoplasm, bony orbital reconstruction, and repair of congenital craniofacial deformities. Because the orbital bones have minimal functional stress, the Micro System provides adequate support. The plates are not apparent through the thin periorbital skin. For bony fixation in the periorbital region, the Micro System appears superior to larger systems and to wire or nonabsorbable sutures.

Adult↗

Beagle pup germinal matrix maturation studies.

Intraventricular hemorrhage, or hemorrhage into the germinal matrix tissues of the developing brain, remains a common problem of preterm infants. The "risk period" for this insult is the first 3-4 postnatal days. We hypothesized that this risk period for hemorrhage is related to rapid perinatal maturation of the germinal matrix vasculature and employed the newborn beagle pup model for the study of this maturation. Newborn beagle pups (n = 30) were anesthetized and systemically perfused with buffered formalin; the brains were removed and prepared for immunohistochemical study. Sections stained with Bandeiraea lectin demonstrated that there was no difference in germinal matrix vessel density between postnatal days 1 and 4. Germinal matrix sections were also stained for antibodies to alpha-smooth muscle actin, collagen IV, collagen V, desmin, factor VIII-related antigen, fibronectin, glial fibrillary acidic protein, laminin, transferrin, and vimentin. Vasculature staining by alpha-smooth muscle actin was not noted until postnatal day 10, and differential staining was detected for antibodies to laminin and collagen V. Quantification of staining intensity by confocal microscopy demonstrated a significant increase in both extracellular matrix components at postnatal day 4 compared with day 1 (p less than 0.05 for both). These basement membrane proteins may add sufficient structural integrity to germinal matrix vessels to prevent capillary rupture and thus intraventricular hemorrhage.

Aging↗

Computer-assisted three-dimensional reconstructions of [14C]-2-deoxy-D-glucose metabolism in cat lumbosacral spinal cord following cutaneous stimulation of the hindfoot.

We report on computer-assisted three-dimensional reconstruction of spinal cord activity associated with stimulation of the plantar cushion (PC) as revealed by [14C]-2-deoxy-D-glucose (2-DG) serial autoradiographs. Moderate PC stimulation in cats elicits a reflex phasic plantar flexion of the toes. Four cats were chronically spinalized at about T6 under barbiturate anesthesia. Four to 11 days later, the cats were injected (i.v.) with 2-DG (100 microCi/kg) and the PC was electrically stimulated with needle electrodes at 2-5 times threshold for eliciting a reflex. Following stimulation, the spinal cord was processed for autoradiography. Subsequently, autoradiographs, representing approximately 8-18 mm from spinal segments L6-S1, were digitized for computer analysis and 3-D reconstruction. Several strategies of analysis were employed: 1) Three-dimensional volume images were color-coded to represent different levels of functional activity. 2) On the reconstructed volumes, "virtual" sections were made in the horizontal, sagittal, and transverse planes to view regions of 2-DG activity. 3) In addition, we were able to sample different regions within the grey and white matter semi-quantitatively (i.e., pixel intensity) from section to section to reveal differences between ipsi- and contralateral activity, as well as possible variation between sections. These analyses revealed 2-DG activity associated with moderate PC stimulation, not only in the ipsilateral dorsal horn as we had previously demonstrated, but also in both the ipsilateral and contralateral ventral horns, as well as in the intermediate grey matter. The use of novel computer analysis techniques--combined with an unanesthetized preparation--enabled us to demonstrate that the increased metabolic activity in the lumbosacral spinal cord associated with PC stimulation was much more extensive than had heretofore been observed.

Animals↗

Thromboxane synthesis inhibitor in a beagle pup model of perinatal asphyxia.

During perinatal asphyxia, cerebral blood flow is markedly reduced in the gray and white matter of the telencephalon. Since previous work has implicated prostaglandins in the control of blood flow, we tested the hypothesis that a thromboxane synthesis inhibitor would improve cerebral blood flow and blunt the metabolic alterations that accompany asphyxia. Forty-three newborn beagles 2-7 days old were anesthetized, ventilated, and randomized to insult (5 minutes of asphyxia) or no insult and received treatment with either the thromboxane synthesis inhibitor CGS 13080 (CIBA-GEIGY Corp.) (0.06 mg/kg/hr i.v. infusion) or saline. Cerebral blood flow was measured in 25 pups. Pups received treatment 30 minutes before insult or no insult. In pups randomized to insult and receiving saline, cerebral blood flow increased during insult in the medulla but decreased elsewhere. Pups randomized to insult and treated with thromboxane synthesis inhibitor had increased cerebral blood flow during insult in all cerebral regions studied. In addition, these pups experienced a significantly higher incidence of intraventricular hemorrhage than did pups randomized to insult and receiving saline. In other experiments with 18 pups, brain extracts were prepared for proton nuclear magnetic resonance spectral analysis of high-energy phosphorylated compounds and lactate levels. In pups exposed to insult and receiving saline, mean +/- SD phosphocreatine concentration fell from 1.9 +/- 0.1 to 0.4 +/- 0.1 mmol/kg, lactate concentration increased from 2.0 +/- 0.5 to 3.3 +/- 0.4 mmol/kg, and the calculated pH fell 0.8 units. There were no differences between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Orbital surgery. The technique of coronal scalp flap approach to the qateral orbitotomy.

Lateral orbitotomy may be performed using a coronal scalp flap to provide exposure of the lateral orbital wall and rim. A coronal incision is made across the scalp. The scalp flap is developed anteriorly to expose the orbital margin from the superior orbital rim to the zygomatic arch. The temporalis muscle is dissected from its bony attachments and bluntly retracted, providing maximal exposure of the lateral orbital wall. The orbitotomy proceeds as required. The case concludes with a layered closure. In selected patients, the coronal scalp flap provides improved exposure and postoperative aesthetics compared with approaches in which the skin and muscle layer are incised directly over the lateral orbit. Complications are infrequent.

Humans↗

Multidisciplinary approach to the management of complex bony and soft tissue orbitocranial disorders.

Orbital reconstructive surgery is entering a new age as progress in surgical techniques and diagnostic imaging are applied to the patient with severe acquired orbital and periorbital deformities. The authors present a series of six patients with orbitocranial neoplasms and congenital and traumatic deformities whose management involved a multidisciplinary approach. Particular emphasis is placed on the use of reformatting two-dimensional orbital scans into three-dimensional images and surgical techniques using composite flaps and periorbital microsurgical vascular anastomoses. Advancements in technology and sophisticated reconstructive surgical techniques have exciting potential. Ophthalmologists can play an important role in this expanding field since they frequently serve as the entry point or provide long-term follow-up to patients with these complex problems.

Adult↗

Computer-designed prostheses for orbitocranial reconstruction.

Three-dimensional imaging is an adjunct to preoperative evaluation and surgical management in some patients with complex anatomic defects of various etiologies. Deformities defined by conventional computerized tomography can be viewed as accurate three-dimensional images calculated from the original scan. The images are viewed on a high-resolution video monitor and can be photographed for a permanent record. A computer-controlled milling device can use these data to fabricate prostheses. The prostheses aid reconstructive surgery through use as an alloplastic implant, as a template to fashion autogenous bone grafts, or as a model for tissue removal. We have utilized three-dimensional imaging in combination with computer-assisted prosthesis manufacture in six patients with complex orbitocranial deformities. Four patients have undergone reconstructive surgery with satisfactory results and no complications thus far. The use of computer-designed prostheses adds a new aspect to orbitocranial reconstructive surgery that facilitates increased accuracy in the correction of anatomic defects.

Adolescent↗

A multidisciplinary approach to orbital neoplasm.

The patient with orbital and periorbital neoplasia requires careful assessment of the extent and biologic activity as well as histopathologic categorization. Treatment is optimal through a multidisciplinary approach involving the ophthalmic surgeon, plastic surgeon, neurosurgeon, head and neck surgeon, and oral surgeon.

Aged↗

The spatial organization of olfactory nerve projections.

The spatial organization of olfactory nerve projections was examined in the rat. The pathway was traced by orthograde transport of HRP following nasal lavage and by retrograde transport of HRP following injections into the olfactory bulb. The results indicated that there was a broad relationship between the epithelium and the olfactory bulb. Specific regions of the olfactory bulb received input from a large region of the epithelium. However, there was evidence that olfactory nerve terminations were not uniformly dense across their terminal fields. The results suggest that there may be finer sorting of olfactory nerves based on functional specificity.

Animals↗

The technique of cranial bone grafts in the correction of posttraumatic orbital deformities.

The technique of split-thickness cranial bone graft for reconstructive orbital surgery, is reported in five patients who sustained extensive orbital trauma. This technique involves exposing the skull via a coronal scalp incision, after which the cranial bone is split in situ along the diploe. The outer table of the cranial bone is then used as a graft to correct orbital defects and other associated bony deformities. Cranial bone grafts have several advantages over other graft sites in orbital reconstruction, including more rapid postoperative recovery, close proximity of donor site to recipient site, and improved survival of cranial bone grafts in experimental studies. Cranial bone grafts are an important source of autogenous tissue for the reconstructive surgeon.

Adolescent↗

Temporal relationship between neurotransmitter release and ion flux during spreading depression and anoxia.

Brain ion homeostasis is severely perturbed during spreading depression of Leao and during anoxia. The ionic composition of the extracellular space changes abruptly and approaches the intracellular concentrations owing to an increase in cell permeability. In spreading depression, synchronous transmitter efflux caused by a depolarization of the presynaptic terminals has been implicated as a possible mechanism that would explain the concomitant movement of ions. Anoxia, having many features in common with spreading depression, may follow the same mechanism. We have measured the concentrations of extracellular potassium with ion-selective microelectrodes and dopamine by in vivo voltammetry with carbon fiber microelectrodes during spreading depression and anoxia to compare the temporal relationship between the release of dopamine and ion movements in the striatum. There is a pronounced release of dopamine during both spreading depression and anoxia. In spreading depression, the sharp increase of potassium concentration that follows an initial smaller and slower increase of potassium is accompanied by the release of dopamine. In anoxia, the dopamine release clearly precedes the fast rise of extracellular potassium concentration. We conclude that in striatum, there is a pronounced dopamine release during spreading depression and anoxia, but that the relationships between ionic changes and transmitter release for these two phenomena are different and probably reflect different mechanisms.

Animals↗

Beagle pup model of brain injury: regional cerebral blood flow and cerebral prostaglandins.

Asphyxia is the most common cause of severe brain injury in very young children, and frequently results in lesions of the periventricular white matter in addition to other neuropathological changes. This study examines the effects of asphyxia on regional cerebral blood flow (rCBF) and the role of prostaglandins (PG's) in its control in the newborn beagle pup. Pups were anesthetized, tracheotomized, paralyzed, artificially ventilated, and randomly assigned to two groups: asphyxial insult produced by discontinuing ventilatory support, and no insult. Experiments for carbon-14-iodoantipyrine autoradiographic determination of rCBF and regional cerebral PG determination were performed on separate groups of pups. These studies demonstrated a significant increase in cortical gray PGE2 levels at a time when rCBF was significantly impaired in response to severe asphyxial insult. No such increase was noted in the periventricular white matter zones.

Animals↗

Blood flow and metabolism in the developing brain.

The newborn brain has mechanisms that act to preserve the blood flow to the brain stem. When challenged with an asphyxial episode, there is a redistribution of blood flow in the brain. The brain stem structures have increased blood flow, and telencephalic structures, particularly white matter, have decreased flow. These changes are made possible in part because the newborn brain stem vascular appears to be much more sensitive to pCO2 than the telencephalic vasculature. In fact, several brain stem regions exhibit a higher sensitivity to CO2 than the adult cortex. Consequently, vessels in this region are able to vasodilate more effectively. In addition, the sympathetic vascular innervation in the newborn brain appears more profuse in the forebrain. So this system could produce a widespread vasoconstruction and participate in the shift of blood flow from the cerebral hemispheres to the brain stem. This capacity to preserve blood flow to the critical brain stem regions may explain, in part, the ability of the neonatal animal to survive long periods of asphyxia. This phenomena might also explain the clinical findings of white matter loss and stroke in the cerebral hemispheres, since these regions seem to be selectively deprived of blood flow during insult. This relationship is summarized in Fig 1.

Animals↗

Mapping of an olfactory receptor population that projects to a specific region in the rat olfactory bulb.

An anatomically distinct group of glomeruli, termed the modified glomerular complex (MGC), is present in the posterior dorsomedial portion of the main olfactory bulb. This region has been strongly implicated as part of the pathway that processes odor cues for suckling in neonatal rat pups. We studied the distribution pattern of olfactory receptor neurons that project to the MGC region after ionophoretic injections of WGA-HRP into the olfactory bulbs of 12-day-old rat pups. HRP label was confined to an identifiable localized region in the MGC of the main olfactory bulb. Label extended over 2-7% of the glomerular sheet of the main olfactory bulb, including the MGC. Olfactory receptor neurons within the olfactory epithelium of the nasal cavity were labeled with HRP ipsilateral to the injected side. Maps constructed of the olfactory epithelium revealed that the labeled neurons occurred within topographically defined regions. Anteriorly, labeled olfactory neurons were confined to a narrow strip medial to the dorsal recess, and, more posteriorly, this strip widened medially along the septal wall and laterally onto a limited area on the nasal turbinates. Only a portion of the receptor population within a region was labeled. The boundaries between labeled and unlabeled regions were sharp. These findings support the concept that the olfactory epithelium is an anatomical mosaic in which receptors with different glomerular projections sites are intermingled. In conjunction with previous evidence on the functional specificity of the MGC, and staining of receptor neuron subgroups with monoclonal antibodies, these findings further suggest that olfactory receptor neurons form a functional mosaic within the olfactory epithelium.

Animals↗