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T McIntosh

Publications and source records attributed to T McIntosh.

At least 19 recordsLinked to original sources
PubMed2003

Age-dependent synuclein pathology following traumatic brain injury in mice.

Synucleins (Syn), a family of synaptic proteins, includes alpha-Syn, which plays a pivotal role in Parkinson's disease and related neurodegenerative diseases (synucleinopathies) by forming distinct brain pathologies (Lewy bodies and neurites). Since traumatic brain injury (TBI) is a poorly understood risk factor for Parkinson's disease, we examined the effects of TBI in the young and aged mouse brain on alpha-, beta-, and gamma-Syn. Immunohistochemical analysis showed that brains from sham-injured young and aged mice had normal alpha- and beta-Syn immunoreactivity (IR) in neuropil of cortex, striatum, and hippocampus with little or no gamma-Syn IR. At 1 week post TBI, the aged mouse brain showed a transient increase of alpha- and beta-Syn IR in the neuropil as well as an induction of gamma-Syn IR in subcortical axons. This was associated with strong labeling of striatal axon bundles by antibodies to altered or nitrated epitopes in alpha-Syn as well as by antibodies to inducible nitric oxide synthase. However, these TBI-induced changes disappeared by 16 weeks post TBI, and altered Syn IR was not seen in young mice subjected to TBI nor in alpha-Syn knockout mice while Western blots confirmed that TBI induced transient alterations of alpha-Syn in the mouse brains. This model of age-dependent TBI-induced transient alterations in alpha-Syn provides an opportunity to examine possible links between TBI and mechanisms of disease in synucleinopathies.

Aging↗
PubMed2000

Effect of chain length and unsaturation on elasticity of lipid bilayers.

Micropipette pressurization of giant bilayer vesicles was used to measure both elastic bending k(c) and area stretch K(A) moduli of fluid-phase phosphatidylcholine (PC) membranes. Twelve diacyl PCs were chosen: eight with two 18 carbon chains and degrees of unsaturation from one double bond (C18:1/0, C18:0/1) to six double bonds per lipid (diC18:3), two with short saturated carbon chains (diC13:0, diC14:0), and two with long unsaturated carbon chains (diC20:4, diC22:1). Bending moduli were derived from measurements of apparent expansion in vesicle surface area under very low tensions (0.001-0.5 mN/m), which is dominated by smoothing of thermal bending undulations. Area stretch moduli were obtained from measurements of vesicle surface expansion under high tensions (>0.5 mN/m), which involve an increase in area per molecule and a small-but important-contribution from smoothing of residual thermal undulations. The direct stretch moduli varied little (< +/-10%) with either chain unsaturation or length about a mean of 243 mN/m. On the other hand, the bending moduli of saturated/monounsaturated chain PCs increased progressively with chain length from 0.56 x 10(-19) J for diC13:0 to 1.2 x 10(-19) J for diC22:1. However, quite unexpectedly for longer chains, the bending moduli dropped precipitously to approximately 0.4 x 10(-19) J when two or more cis double bonds were present in a chain (C18:0/2, diC18:2, diC18:3, diC20:4). Given nearly constant area stretch moduli, the variations in bending rigidity with chain length and polyunsaturation implied significant variations in thickness. To test this hypothesis, peak-to-peak headgroup thicknesses h(pp) of bilayers were obtained from x-ray diffraction of multibilayer arrays at controlled relative humidities. For saturated/monounsaturated chain bilayers, the distances h(pp) increased smoothly from diC13:0 to diC22:1 as expected. Moreover, the distances and elastic properties correlated well with a polymer brush model of the bilayer that specifies that the elastic ratio (k(c)/K(A))(1/2) = (h(pp) - h(o))/24, where h(o) approximately 1 nm accounts for separation of the headgroup peaks from the deformable hydrocarbon region. However, the elastic ratios and thicknesses for diC18:2, diC18:3, and diC20:4 fell into a distinct group below the correlation, which showed that poly-cis unsaturated chain bilayers are thinner and more flexible than saturated/monounsaturated chain bilayers.

Biophysical Phenomena↗
PubMed1999

Genetic approaches to neurotrauma research: opportunities and potential pitfalls of murine models.

Genetic strategies provide new ways to define the molecular cascades that regulate the responses of the mammalian nervous system to injury. Genetic interventions also provide opportunities to manipulate and control key molecular steps in these cascades, so as to modify the outcome of CNS injury. Most current genetic strategies involve the use of mice, an animal that has not heretofore been used extensively for neurotrauma research. Therefore, one purpose of the present review is to consider how mice respond to neural trauma, focusing especially on recent information that reveals important differences between mice and rats, and between different inbred strains of mice. The second aim of this review is to provide a brief introduction to the opportunities, caveats, and potential pitfalls of studies that use genetically modified animals for neurotrauma research.

Animals↗
PubMed1998

Magnetic resonance imaging analysis of lumbar disc changes below scoliosis fusions. A prospective study.

STUDY DESIGN: The authors of this prospective study examined the preoperative and 3-year postoperative magnetic resonance images of 14 patients undergoing anterior and posterior fusion and/or posterior fusion only for scoliosis. All magnetic resonance images were ready by two independent neuroradiologists, who were blinded to the purposes of the study, for the presence of disc narrowing, signal decrease on T2, or herniated nucleus pulposus before and after surgery. Particular attention was paid to the disc changes at the level directly below the end vertebral level of the fusion and two levels below the fusion in the lumbosacral spine existing before surgical intervention. OBJECTIVES: To evaluate the potential for disc degeneration distal to long scoliosis fusions with end fusion levels in the mid to lower lumbar spine. SUMMARY OF BACKGROUND DATA: The determination of end levels of fusion for contructs presently used to manage adult scoliotic deformity has been evaluated in terms of correction of curvature and late decompensation in coronal and sagittal plane balance after fusion. However, the natural history of the caudal, free-motion segments in terms of degeneration and/or correlation with pain has not yet been addressed. METHODS: Fourteen patients undergoing scoliosis fusion underwent magnetic resonance imaging before surgery and approximately 3 years after surgery. The scans were reviewed by two independent neuroradiologists who looked at three degenerative indices at the disc below the area of scoliosis fusion. The authors analyzed rates of change of the three degenerative indices in the pre- and postoperative magnetic resonance images and created associations between the observed changes on the magnetic resonance images and the clinical outcomes of pain, the presence or absence of solid fusion, and the need for repeat surgery. RESULTS: Estimates of the rates of change of the three degenerative indices one or two levels below the fusion were as follow: the chance of disc narrowing, .2-34%; the chance of a decreasing signal on T2, 5-54%, with a 23% incidence among this group; and the chance of herniated nucleus pulposus, 0-34%. There was a significant correlation between the presence of back and/or leg pain and the signal decrease one level below the fusion (P = .04). CONCLUSIONS: If these results are corroborated in a larger sample size, surgeons who manage deformity may have to consider altering fusion levels at the time of fusion based on magnetic resonance imaging predictors. The present data may help to inform patients about the risk of developing junctional degenerative changes and potential symptoms from these changes below scoliosis fusions.

Adolescent↗
PubMed1998

Initial Clinical Experience of a Novel Device (the ÒFriend CatheterÓ) for Local Anesthetic Delivery Around Indwelling Arterial Sheaths.

The removal of femoral arterial sheaths, particularly after they have been in place for some hours, is a source of pain for patients undergoing invasiveive cardiac procedures. Methods of reducing this pain include systemic sedatives, analgesics and local anesthetic. We tested a new disposable plastic device, called the ÒFriend,Ó designed to reduce pain associated with sheath removal. The Friend wraps around a standard 8 Fr sheath allowing local anesthetic infiltration through side holes into local tissue. METHODS: Seventy-two patients undergoing interventional procedures were randomized to 3 groups for anesthetic administration just prior to sheath removal. Group 1 (control) received no local anesthetic. Group 2 (local) received 10 ml of lignocaine directly infiltrated with syringe and needle around the sheath. Group 3 (Friend) had the Friend inserted with the sheath and 10 ml of lignocaine was delivered via the device. Pain around the sheath was assessed prior to, during and just after, sheath removal using a 5 point verbal scale. RESULTS: Sixty-two patients completed the study. There were no serious complications related to the Friend device. The Friend group patients had significantly less pain associated with sheath removal than the control group. (Mean pain difference 1.28 vs. 0.34, p = 0.04). Pain scores in group 2 (local) did not differ significantly from the control group. The additional estimated cost involved in using the Friend was $16.93 per patient. CONCLUSIONS: The Friend device is a new, inexpensive and safe method of reducing pain associated with removal of arterial sheaths after cardiac interventional procedures.

Journal Article↗
PubMed1997

Impact acceleration injury in the rat: evidence for focal axolemmal change and related neurofilament sidearm alteration.

Recently we reported that traumatic brain injury evokes local changes in the axolemma's permeability, in concert with local cytoskeletal changes involving neurofilament (NF) compaction and sidearm loss, all of which contribute to the genesis of reactive axonal change. Since it was of concern that these events may be either injury model- or species-specific, we sought to address these phenomena in a different but well-characterized animal model and species. Further, to provide more compelling insight into the potential for NF compaction and sidearm alteration, we also employed antibodies specific for the NF rod domains, which are readily visualized only when the NF sidearms are disturbed. Rats were subjected to impact acceleration injury. To assess the potential for altered axolemmal permeability, 5 animals received intrathecal horseradish peroxidase (HRP), normally excluded by the intact axolemma. To assess the potential for NF sidearm alteration, another 14 animals were processed for the visualization of antibodies targeting the NF rod domain at 5 minutes (min) to 24 hours (h) postinjury. All animals were evaluated at the LM and EM levels. Those animals receiving intrathecal HRP showed immediate focal alterations in the axolemma's permeability to the normally excluded tracer. Over a 2 h period, these axons demonstrated NF compaction. Antibodies targeted to the rod domains revealed focal intra-axonal immunoreactivity in sites closely correlated with those showing altered axolemmal permeability. These same sites also demonstrated evidence of NF compaction and sidearm loss/perturbation. Collectively, these findings suggest that occurrence of altered axolemmal permeability and concomitant cytoskeletal change are features common to traumatic brain injury in various animal models and species. Further, these studies underscore the utility of antibodies targeting the rod domain for the early detection of traumatically induced reactive change.

Animals↗
PubMed1996

Temporal and spatial characterization of neuronal injury following lateral fluid-percussion brain injury in the rat.

The pattern of neuronal injury following lateral fluid-percussion (FP) brain injury in the rat was systematically characterized at sequential time points to identify selectively vulnerable regions and to determine the temporal contribution of primary and delayed neuropathological events. Male Sprague-Dawley rats (n = 28) were killed 10 min, 2 h, 12 h, 24 h, 4 days, and 7 days following a lateral FP brain injury of moderate severity (2.2 atm), or 24 h after a sham injury. Brain sections were stained and analyzed using Nissl, acid fuchsin, and silver staining methods to identify regions with injured neurons or with visible lesions. Extensive numbers of acid fuchsin or silver-stained neurons were observed as early as 10 min after the FP brain injury in regions extending from the caudate/putamen to the pons. The frequency of injured neurons was greatest in the ipsilateral cortex, hippocampus, and thalamus, and a visible loss of Nissl-stained neurons was observed in these regions beginning at 12 h after the FP brain injury. Acid fuchsin-stained neurons were restricted to the same brain regions for all of the survival periods and gradually decreased in numbers between 24 h and 7 days after injury. These findings suggest that lateral FP brain injury in the rat produces a combination of focal cortical contusion and diffuse subcortical neuronal injury, which is present within minutes of the impact, progresses to a loss of neurons by 12 h, and does not markedly expand into other brain regions with survival periods up to 7 days. Furthermore, the acute onset and rapid evolution of the neuronal injury process may have important implications when considering a window of opportunity for pharmacological intervention.

Animals↗
PubMed1995

Health outcome assessment before and after adult deformity surgery. A prospective study.

STUDY DESIGN: Fifty-five patients undergoing surgery for adult spinal deformity assessed their health status using a generic health outcome instrument before surgery and at an average of 2 years after surgery. OBJECTIVE: To assess whether adult spinal deformity surgery is a useful intervention when patients evaluate their own perception of health. The Medical Outcomes Survey Short Form-36, a validated generic health outcome assessment form, was used to measure patient's health status. SUMMARY OF BACKGROUND DATA: Surgery for adult scoliosis is technically demanding. No study that we are aware of uses a generic health outcome instrument in a prospective manner to compare patients' perception of their health after adult scoliosis surgery. The Medical Outcomes Survey Short Form-36 has been validated in multiple studies assessing other medical conditions and was found to be reliable, comprehensive, brief, and generic. METHODS: Sixty-eight adult patients undergoing surgery for adult spinal deformity were prospectively enrolled. Fifty-five patients were available to complete the Medical Outcomes Surgery Short Form-36 after surgery. The scores of the health profile were compared before and after surgery. The results of patients younger than 40 years were compared with those of patients older than 40 years. The results of patients younger than 40 years were compared with those of patients older than 40 years. The results of patients fused to more caudal end vertebral levels ((L4, L5)5) were compared with those who were fused to more cranial end vertebral levels. The results of patients without complications after surgery were compared with those of patients with complications after surgery. RESULTS: Average follow-up period was 22.5 months (minimum 12 months) in 82% of 68 patients. Statistically significant improvements were seen in postoperative scores for physical function, social function, bodily pain, and perceived health change. We found no significant differences in self-reported health function parameters related to age ( > 40 vs. < 40), end vertebral level of fusion, or presence of complications after surgery. CONCLUSIONS: Applying a generic health outcome instrument to adult spinal deformity surgery shows that adult scoliosis surgery significantly improves patient self-reported health assessment and function. Beneficial results do not appear to deteriorate with age or more caudal end vertebral levels of fusion. Future studies combining disease-specific outcomes analysis and generic health surveys to assess end results of adult spinal deformity surgery will be useful.

Adult↗
PubMed1994

Kynurenate is neuroprotective following experimental brain injury in the rat.

Pharmacologic inhibition of excitatory amino acid neurotransmission improves physiologic, metabolic, and neurobehavioral outcome following experimental brain trauma. However, no studies to date have demonstrated pharmacologically-induced attenuation of histopathological changes associated with experimental brain injury models. The present study examined the effects of kynurenate, an NMDA and non-NMDA receptor antagonist, on neuronal survival in the hippocampus after lateral fluid-percussion brain injury in the rat. Animals (n = 10/treatment) randomly received an intravenous injection of either kynurenate (300 mg/kg) or buffer (equal volume) 15 min following fluid-percussion brain injury of moderate severity. Two weeks after injury, animals were sacrificed and neuronal cell loss in the hippocampus was examined with Nissl staining. Selective loss of neurons in the CA3 region of the hippocampus, which has previously been characterized in this model of brain injury, was found to be significantly attenuated following kynurenate treatment (P < 0.05). These data suggest that pharmacologic compounds which are known to have beneficial effects on neurobehavioral and physiological outcome following brain injury may also significantly attenuate post-traumatic neuronal cell loss. Our results also support other recent data that pharmacological intervention with an excitatory amino acid receptor antagonist may be of therapeutic value in the treatment of brain injury.

Animals↗
PubMed1993

Early versus late replacement of autotransfused blood in elective spinal surgery. A prospective randomized study.

The use of autologous blood is a well established and extremely popular technique to decrease the necessity for homologous transfusions and the attendant risks of hepatitis, HIV, and HTLV--I/II infections. The most beneficial timing for autologous reinfusion of predonated blood remains unknown. The present study was undertaken to determine the optimal timing of autologous blood reinfusion in elective spinal surgery. Fifty-seven patients were prospectively individually randomly allocated into early versus delayed reinfusion groups prior to undergoing elective spinal surgery by a single surgeon. Three surgical subgroups were entered into the study: anterior/posterior (A/P) spinal fusion patients, posterior thoracolumbar scoliosis fusion patients (PSF), and degenerative posterior lumbar fusion patients (LF). Randomization was successful in that three was no significant difference in male to female ratio, age, preoperative hemoglobin, or number of units predonated between the early and delayed reinfusion groups. Likewise, there was no significant difference in the details of the operative procedure when compared as a group for the early versus delayed reinfusion groups. A significant increase in the postoperative day #1, 2 and 3 hemoglobin was seen in the early reinfusion group, while there was no significant difference seen in the postoperative day #7 hemoglobin between the early versus delayed reinfusion group. There was no effect of surgical grouping on these significant comparisons. Earlier patient mobilization was also seen in the early reinfusion groups for the A/P and PSF groups. There was no difference in patients' subjective evaluation of satisfaction and discomfort between the early or delayed reinfusion groups as determined by blinded interview on days 1, 3, 5, and 7 postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Vasoactive neurochemicals identified in omentum: a preliminary report.

There has been increasing interest in biologic, immunologic, and chemical activity originating from omental tissue. Since clinical improvement has been observed in some patients very shortly after surgically transposing their omentum to the spinal cord or brain, the question arose as to whether neurochemicals might be present in omental tissue; a possible explanation for some of these neurological changes. This paper reports the presence of vasoactive neurochemicals in canine omental tissue. It remains unclear, however, whether the omentum produces or simply concentrates these and other neurochemicals.

Animals↗
PubMed1986

Elevation of circulating beta-endorphin levels with concomitant depression of immune parameters after traumatic injury.

Immunosuppression is frequently observed after traumatic injury, and is associated with the subsequent development of sepsis. Although a number of factors such as age, nutritional status, and the degree of injury have been related to the severity of the immunosuppression that occurs, the physiologic alterations leading to immunosuppression are not well defined. We hypothesized that changes in the endogenous opiate peptides, such as beta-endorphin, might contribute to changes in the immune system following injury. Levels of circulating beta-endorphin, responsiveness to the mitogen PHA, and the frequency of circulating T11, T4, and T8 cells were measured in trauma patients hospitalized in a surgical intensive care unit. beta-endorphin levels were elevated during the first 4 days after trauma (134.1 +/- 22.5 vs. 49.3 +/- 4.3 pg/ml, mean +/- S.E., patient vs. control; p less than 0.001). During the same time period patient PHA response (10,852 +/- 3,775 vs. 28,147 +/- 12,078; p less than 0.05), and the per cent of T4 positive (31.2 +/- 2.6 vs. 47.0 +/- 1.4; p less than 0.001) cells were lower than controls. These parameters were not significantly different from control values when measured at later times. Thus we conclude there is a temporal association of depressed immune parameters and elevated beta-endorphin levels after traumatic injury.

Endorphins↗
PubMed1985

Plasma beta-endorphin levels in primary aldosteronism.

Excessive production of an as yet unidentified aldosterone-stimulating factor may cause idiopathic hyperaldosteronism (IHA). This putative factor may be related to proopiomelanocortin-derived peptides, some of which have aldosterone-stimulating properties. The present study evaluated plasma beta-endorphin, ACTH, cortisol, and aldosterone levels in patients with IHA (n = 10), aldosterone-producing adenomas (n = 4), essential hypertension (n = 11), and normal subjects (n = 10). Plasma and urinary hormone measurements were obtained at timed intervals during an isocaloric, fixed electrolyte intake (Na+, 128 meq/day; K+, 80 meq/day) in a metabolic unit. Plasma for beta-endorphin assay was preincubated with sepharose-bound anti-beta-lipotropin to remove beta-lipotropin that cross-reacted with the beta-endorphin RIA. Mean +/- SE plasma beta-endorphin levels at 0800 h were elevated in IHA patients (47 +/- 13 fmol/ml) compared to those in aldosterone-producing adenoma (25 +/- 9), essential hypertension (16 +/- 1), and normal control (20 +/- 2; P less than 0.05) subjects. Plasma ACTH, plasma cortisol, and urinary cortisol levels were not different in these four groups. These data support the hypothesis that excess production of either beta-endorphin or related proopiomelanocortin-derived peptides may function as aldosterone secretogogue(s) in IHA.

18-Hydroxycorticosterone↗
PubMed1984

Temporal characteristics of cortisol metabolism in adrenalectomized primates.

The rhythmicities observed in the plasmatic levels of cortisol are generally attributed to rhythms of production and release of the hormone. Since the plasmatic concentration of any given substance is a function of its production and its removal from the circulation, it is conceivable that the metabolism of cortisol also occurs in an oscillating fashion. To test this hypothesis Rhesus monkeys were submitted to bilateral adrenalectomy; cortisol was replaced at a constant infusion rate while blood was sampled at hourly intervals for the measurement of cortisol plasma levels. Rhythmic oscillations in the cortisol levels were observed. These rhythms exhibited two major components: a circadian and an ultradian component. The authors suggest that these rhythms be considered whenever normal or pathologic hormone rhythmicities are analyzed.

Adrenalectomy↗
PubMed1984

Elevated plasma levels of beta-endorphin in a group of women with polycystic ovarian disease.

The relationship of endogenous opiates in patients with polycystic ovarian disease (PCOD) and their influence on body weight was studied. The study group consisted of 19 women with PCOD. They were amenorrheic, hirsute, and hyperandrogenic, and their average weight was 124% of the ideal body weight. They had luteinizing hormone/follicle-stimulating hormone ratios greater than or equal to 2. The control group consisted of ten women with regular ovulatory menses. Plasma beta-endorphin (beta-EP) was measured by using a very specific radioimmunoassay. beta-Lipotropin (beta-LPH) was entirely removed from the sample by preincubation of the plasma with rabbit anti-beta-LPH/Sepharose complex (Pharmacia, New Brunswick, NJ). The mean +/- standard deviation of the plasma beta-EP in the control group was 70.18 +/- 18.06 pg/ml, and the mean +/- standard deviation of beta-EP in the study group was 185.6 +/- 93.4 pg/ml, which was significantly higher than the control levels (P less than 0.001). A significant correlation was also found between plasma beta-EP level and the patient's weight in the PCOD group (r = 0.462, P = 0.025). The data from this study suggest that the elevated levels of endogenous opiates may be involved in the pathophysiology of PCOD and be related to inappropriate secretion of gonadotropins influencing body weight.

Adolescent↗