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Biomedical subjects

J F Harrington

Publications and source records attributed to J F Harrington.

At least 19 recordsLinked to original sources
PubMed2003

Early neutrophilic expression of vascular endothelial growth factor after traumatic brain injury.

The formation of edema after traumatic brain injury (TBI) is in part associated with the disruption of the blood-brain barrier. However, the molecular and cellular mechanisms underlying these phenomena have not been fully understood. One possible factor involved in edema formation is vascular endothelial growth factor (VEGF). This growth factor has previously been demonstrated to increase the blood-brain barrier permeability to the low molecular weight markers and macromolecules. In this study, we analyzed the temporal changes in VEGF expression after TBI in rats. In the intact brain, VEGF was expressed at relatively low levels and was found in the cells located close to the cerebrospinal fluid space. These were the astrocytes located under the ependyma and the pia-glial lining, as well as the epithelial cells of the choroid plexus. In addition, several groups of neurons, including those located in the frontoparietal cortex and in all hippocampal regions, were VEGF-positive. The pattern of VEGF-immunopositive staining of neurons and choroidal epithelium suggested that in these cells, VEGF binds to the cell membrane-associated heparan sulfate proteoglycans. Following TBI, there was an early (within 4 h post-injury) increase in VEGF expression in the traumatized parenchyma associated with neutrophilic invasion. The ipsilateral choroid plexus appeared to play a role in facilitating the migration of neutrophils from blood into the cerebrospinal fluid space, from where many of these cells infiltrated the brain parenchyma. VEGF-immunopositive staining of neutrophils resembled haloes and was found ipsilaterally within the frontoparietal cortex and around the velum interpositum, a part of the subarachnoid space. These haloes likely represent the deposition of neutrophil-derived VEGF within the extracellular matrix, from where this growth factor may be gradually released during an early post-traumatic period. The maximum number of VEGF-secreting neutrophils was observed between 8 h and 1 day after TBI. In addition, from 4 h post-TBI, there was a progressive increase in the number of VEGF-immunoreactive astrocytes in the ipsilateral frontoparietal cortex. The maximum number of astrocytes expressing VEGF was observed 4 days after TBI, and then the levels of astroglial VEGF expression declined gradually. Early invasion of brain parenchyma by VEGF-secreting neutrophils together with a delayed increase in astrocytic synthesis of this growth factor correlate with the biphasic opening of the blood-brain barrier and formation of edema previously observed after TBI. Therefore, these findings suggest that VEGF plays an important role in promoting the formation of post-traumatic brain edema.

Animals↗
PubMed2001

Far lateral disc excision at L5-S1 complicated by iliolumbar artery incursion: case report.

OBJECTIVE AND IMPORTANCE: Paramedial approaches to far lateral discs at the L5-S1 space joint have advantages but may also bring the surgical space closer to large branch arteries of the internal iliac artery. I report incursion into an iliolumbar artery that required laparotomy to control hemorrhage. Surgeons performing extraforaminal disc explorations at L5-S1 need to evaluate preoperative magnetic resonance imaging scans for an enlarged iliolumbar artery near the disc space. CLINICAL PRESENTATION: The patient presented with a right L5 radiculopathy and a far lateral disc at L5-S1, as indicated by analysis of her magnetic resonance imaging scan. INTERVENTION: A midline incision and an extraforaminal exposure were performed. Arterial bleeding occurred when an anular disc fragment was removed with a pituitary rongeur under direct vision with microscopic magnification. Emergency laparotomy demonstrated hemorrhage from a branch of the internal iliac artery 2 cm from its origin. CONCLUSION: Iliolumbar artery variants may be at the margins of extraforaminal disc exposure at L5-S1. Preoperative magnetic resonance imaging scans should be evaluated for this vasculature structure.

Adult↗
PubMed2000

Herniated lumbar disc material as a source of free glutamate available to affect pain signals through the dorsal root ganglion.

STUDY DESIGN: Combined prospective human cohort and prospective controlled animal model. OBJECTIVES: To determine whether free glutamate is available in herniated disc material in concentrations sufficient to diffuse to glutamate receptors and affect the activity of neurons in the dorsal root ganglion that may transmit pain information. SUMMARY OF BACKGROUND DATA: The severity of lumbar radicular pain cannot be fully explained by physical pressure on nerve roots or ganglions. In experimental models, inflammatory processes are relatively modest under conditions of disc herniation. The hypothesis for the current study was that the proteoglycan link and core proteins, which contain high fractions of acidic amino acids, may be a source of glutamate when enzymatically degraded in an environment without glutamate reuptake systems. Glutamate would be free to diffuse to the dorsal root ganglion to affect glutamate receptors. METHODS: Disc material was harvested during surgery from herniated and nonherniated portions in patients undergoing elective lumbar disc surgery and subjected to immunohistochemistry and high-performance liquid chromatography for assessment of the presence of extracellular disc matrix glutamate. Miniosmotic pumps with differing concentrations of radiolabeled glutamate based on human data were implanted in the rat epidural space for 72 hours and dorsal root ganglion (DRG) in the region were harvested. RESULTS: Densitometry of disc matrix demonstrated immunohistochemical evidence for significant extracellular glutamate (P < 0.002). High performance liquid chromatography showed significant concentrations of glutamate in disc material and significantly more in herniated than in nonherniated disc material (P < 0.05). Significant radiolabeling of the dorsal root ganglion after epidural glutamate infusion was found at concentrations two orders of magnitude below measured disc glutamate levels. Autoradiography demonstrated radiolabeling of adjacent DRG. CONCLUSIONS: Glutamate originating from degenerated disc proteoglycan may diffuse to the dorsal root ganglion and effect glutamate receptors. Consideration may be given to treating disc radiculopathy with epidural glutamate receptor antagonists.

Adult↗
PubMed1996

Chiasmal herniation as a complication of bromocriptine therapy.

INTRODUCTION: Medical treatment of macroprolactinomas with dopamine agonists decreases tumor mass and improves visual defects. We report an unusual complication of a macroprolactinoma responding to bromocriptine: a visual field defect caused by downward herniation of the optic chiasm. MATERIALS AND METHODS: A 64-year-old woman was found to have a 4.5 cm macroprolactinoma with superior displacement of the optic chiasm, bitemporal hemianopia, and serum prolactin concentration (P) of 17,060 micrograms/L. Bromocriptine was initiated at 2.5 mg/day and increased to 7.5 mg/day over 2 months. RESULTS: After 2 months, visual fields improved significantly and tumor height decreased to 3 cm with resolution of the optic chiasm displacement. P decreased to 1,180 micrograms/L. After 5 months of therapy, visual fields were normal, and P was 8 micrograms/L. After 8 months of therapy, new bilateral visual defects were observed. Magnetic resonance imaging (MRI) revealed further decrease of the tumor height to 1.5 cm, and inferior and leftward traction of the optic chiasm as the probable mechanism for the new visual field deficit. P was < 1 microgram/L. Bromocriptine was decreased to 5 mg/day to allow reduced traction on the optic chiasm and its blood supply. Over the next 4 months, visual field abnormalities resolved. CONCLUSIONS: We report the development of a visual field abnormally that is explained by chiasmal herniation caused by a shrinking macroprolactinoma. This complication resolved with a decrease in the bromocriptine dose. We suggest that patients undergoing bromocriptine therapy for macroprolactinomas be followed for this potential complication.

Bromocriptine↗
PubMed1995

Recovery and complications after tonsillectomy in children: a comparison of ketorolac and morphine.

Ninety-six children received morphine 0.1 mg/kg (n = 47) or ketorolac 1 mg/kg (n = 49) intravenously (IV) in a prospective, randomized, double-blind fashion, after tonsillectomy. Recovery variables and complications were recorded while subjects were in the hospital and parent(s) were contacted 24 h and 14 days after surgery. There were no differences in demographics, surgical management, awakening time, oxygen requirements, or time to readiness for postanesthesia care unit (PACU) discharge or discharge home between the two groups. Ketorolac subjects had fewer emetic episodes than morphine subjects (median 1 vs 3; P = 0.006) and were less likely to have more than two episodes of emesis after PACU discharge (9/49 vs 22/47; P = 0.007). Ketorolac subjects had more major bleeding (bleeding requiring intervention; 5/49 vs 0/47, one-tailed P = 0.03) and more bleeding episodes (0.22 episodes/subject vs 0.04 episodes/subject, P < 0.05) in the first 24 h after surgery, but no greater overall incidence of bleeding than the morphine subjects. In children having tonsillectomy, ketorolac, compared to morphine, reduced the number of emetic episodes after PACU discharge, but did not hasten awakening, readiness for PACU discharge or discharge home, and increased the likelihood of major bleeding in the first 24 h after surgery.

Analgesics, Non-Narcotic↗
PubMed1995

Spinal epidural cavernous angioma presenting as a lumbar radiculopathy with analysis of magnetic resonance imaging characteristics: case report.

Epidural cavernous angiomas are apparently rare lesions. We present an unusual case of chronic lumbar radiculopathy secondary to an epidural cavernous hemangioma extending into the intervertebral foramen. Few such reports have had the benefit of modern neuroimaging techniques to aid in preoperative diagnosis, and, therefore, magnetic resonance imaging of these lesions has not been extensively described. This article discusses the implications of the clinical presentation of the patient and reviews the characteristic magnetic resonance imaging appearance of this lesion garnered from this case and from a review of the literature.

Adult↗
PubMed1993

Regional blood-brain lactate influx.

Regional blood-to-brain lactate transport was studied in chloral hydrate anesthetized rats using the single pass, dual-label, indicator fractionation, right atrial injection method. Lactate influx was resolved into two components, a saturable, stereospecific (to the L-enantiomer) component and a non-saturable, non-stereospecific diffusional component. The saturable component was found to have a low efficiency and moderate capacity with transport affinity coefficients between 6 and 14 mM and transport maxima of 23-40 mumol/100 g/min in the various brain regions. Lactate transport was not inhibited by probenecid. The diffusional component was determined from D-lactate influx measurements and the regional linear diffusion coefficients ranged from 0.020 to 0.036 ml/g/min. At the usual levels of plasma lactate (1-1.5 mM) these two influx components were about equal. The relative contribution of the non-stereospecific diffusional component was increased at higher plasma lactate concentrations. Lactate clearance, estimated by the total apparent permeability x surface area products was between 6 and 8 ml/100 g/min.

Animals↗
PubMed1992

[Effect of metabolic stress on the release of glutamic acid and GABA in the brain tissue of Mongolian hamsters].

The concentrations of glutamic acid and GABA were determined in the brain tissue in gerbils under conditions simulating "metabolic stress", that is ischaemia, aglycaemia and anoxia. The material for the determinations was taken from fragments of the hippocampus incubated under these conditions in artificial cerebrospinal fluid, and the concentrations of these neurotransmitters were determined by histochemical methods in vitro. The release of glutamic acid and GABA into the extracellular space increased with longer duration of the incubation in a linear fashion in all experimental groups and was most pronounced in ischaemia. In case of calcium absence in the extracellular space inhibition was observed of the release of these neurotransmitters which suggested an important role of bivalent cations in the regulation of the studied process, especially under control conditions. During anoxia and ischaemia a considerable part of the release of glutamic acid and GABA seems to be calcium-independent which may suggest presence of additional sources of release of the amino acid neurotransmitters, apart from their release from the direct pool. It is possible that these sources are activated during metabolic stress involving nerve cells.

Animals↗
PubMed1991

Disc herniation in cervical fracture subluxation.

Previous reports of computed tomographic scan with contrast myelography in cervical spinal cord injury have shown a rate of disc herniation of less than 5%. We hypothesized that injuries associated with forces adequate to cause bone or ligamentous injury in the region of the disc space could be associated with higher and more significant rates of disc herniation. Thirty-seven consecutive traumatic midcervical fracture subluxations were reviewed. Fracture subluxation was defined by fracture of the facet joints, pedicles, or vertebral bodies or more than 3.5 mm subluxation from C2-C3 to C7-T1. Reduction was achieved in 97% and was not associated with neurological deterioration. On the basis of plain films, tomograms, and plain computed tomographic scans, the injuries were classified as flexion dislocation, flexion compression, compression burst, or extension injuries. Twenty-five computed tomographic scans with contrast myelograms and one magnetic resonance imaging scan were obtained. All patients with partial neurological deficits were studied. A herniated disc was defined as that which deformed the thecal sac and/or nerve roots. Retrospectively, a neuroradiologist reviewed the studies for the presence of herniated disc. Disc herniation was seen at the level of injury in 9 (35%) patients and not seen in other patients. Forty-seven percent of the patients with partial deficits had herniated discs. Herniated disc was seen most frequently in flexion dislocation and flexion compression injuries. Three patients (20%) with partial deficits underwent discectomy. Patients with partial spinal cord injury and discectomy, on average, improved more than other patients with partial spinal cord injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Improvement of pituitary function after surgical decompression for pituitary tumor apoplexy.

Hypopituitarism is a major manifestation of pituitary adenoma apoplexy. We postulated that the acute deterioration in pituitary function may be caused by compression of portal vessels and the pituitary stalk, secondary to a sudden increase in intrasellar contents. If this were the case, one would predict improvement in pituitary function to occur after surgical decompression. We studied pituitary function in eight patients presenting with the clinical syndrome of pituitary adenoma apoplexy before and on multiple occasions after urgent surgical decompression. Partial or complete hypopituitarism was seen in all subjects at the time of presentation. Serum cortisol levels were inappropriately low (5.9 +/- 1.4 micrograms/dL; 162.8 +/- 38 nmol/L) for the degree of stress in seven patients and appropriately elevated in only one subject (55.3 micrograms/dL; 1525.7 nmol/L). High normal increments in cortisol levels were noted in three subjects given test doses of cosyntropin. Patients were given glucocorticoids before, during, and for 2 days after surgery. Serum cortisol concentrations measured on or after the third day when glucocorticoids had already been stopped were normal in seven subjects and consistently low in one. These seven subjects were discharged on no replacement and were subsequently documented by dynamic testing to have normal pituitary-adrenal function. Gonadal function improved in two of four men and in one of two women who had hypogonadism on presentation. Improvement in thyroid function was documented in two of three subjects with preoperative hypothyroidism. Gradual improvement and almost complete resolution of the neuroophthalmological abnormalities occurred days to weeks after decompression. These observations demonstrate that urgent surgical decompression after pituitary tumor apoplexy was associated with improvement not only in neurological defects but also in pituitary function. The rapid improvement in pituitary function indicates not only that the hypopituitarism was reversible, but also that it might be caused by compression of the portal circulation and pituitary stalk by the sudden increase in intrasellar contents.

Adrenocorticotropic Hormone↗
PubMed1990

Iconicity and sign vocabulary acquisition.

This study was designed to investigate learning and retention of isolated sign vocabulary as a function of sign classification (iconic, opaque, or abstract). The subjects were 28 hearing college students naive to sign vocabulary. They were drilled with 30 signs from American Sign Language that had been classified as iconic, opaque, or abstract. Training was conducted using two different media: computer-assisted instruction and videotaped presentation. Performance scores for the three types of signs were significantly different. Scores were consistently higher for iconic signs, regardless of the training mode. The videotaped presentation mode produced the greatest consistency in scores. The results of this study support the notion that it is easier for beginning students of sign language to learn and retain iconic signs.

Adult↗
PubMed1989

Isolated sign vocabulary acquisition by hearing adults: CAI vs. videotaped presentation.

The present study was designed to examine receptive learning of 30 ASL signs using two teaching modes. Subjects were 28 college students with normal hearing, naive to sign language, who were trained under computer-assisted instruction (CAI) or through videotaped presentation (VT). The results indicated significantly (p less than .01) higher scores under the VT condition when sign learning and retention were probed three and 10 days after training.

Adult↗
PubMed1984

Effects of hypersensitivity to a halothane metabolite on halothane-induced liver damage.

The effect of immunologic hypersensitivity to a metabolite of halothane (trifluoroacetate) on the halothane-hypoxia-induction model was tested in mice and rats. Male Fisher 344 rats (200 g) were immunized with ovalbumin-trifluoroacetate (OVA-TFA) and the time course of the delayed hypersensitivity response determined. The animals had a peak response between 4 and 6 weeks after immunization. Rats were immunized with OVA-TFA, OVA, or saline 5 weeks before being anesthetized. Ten days before anesthesia, the animals were started on 0.1% phenobarbital in the drinking water. The animals were anesthetized with 1% halothane and 14% oxygen for 2 h. Hypersensitivity to TFA had no effect on the liver damage in either the mouse or the rat. These results do not rule out an immunologic vector in halothane hepatitis but make the involvement of TFA unlikely.

Animals↗