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Biomedical subjects

E McCracken

Publications and source records attributed to E McCracken.

12 recordsLinked to original sources
PubMed2001

White matter damage following systemic injection of the mitochondrial inhibitor 3-nitropropionic acid in rat.

Oxidative stress has been implicated as a pathogenic mediator of neuronal perikarya cell death. Axons and oligodendrocytes, components of white matter, could also be vulnerable to oxidative damage. An experimental model of oxidative stress was induced by systemic injection of 3-nitropropionic acid (3-NPA). Animals received an i.p. injection of 10, 15, 20 or 30 mg/kg 3-NPA or vehicle and were killed 24 h later. 3-NPA produced a concentration-dependent increase in axonal pathology within the striatum reflected by the amount of beta-APP and SNAP-25 accumulation. Axonal damage was anatomically coincident with the neuronal lesion. There was no neuronal or axonal damage in the subcortical white matter or cerebral cortex in any of the animals treated with 3-NPA. Manganese superoxide dismutase (Mn-SOD) immunoreactivity was present in the vehicle and all 3-NPA treated groups. The amount of Mn-SOD cellular staining was concentration-dependently increased within the striatum supporting a role for oxidative stress in the mechanism of 3-NPA neurotoxicity. Oligodendrocyte-like cells within the subcortical white matter were immunopositive for calpain-mediated spectrin breakdown products and increased in a concentration-dependent manner. Therefore in this experimental model, mitochondrial inhibition may lead to the initiation of oxidative stress and calpain activation, which could mediate cytoskeletal breakdown in axons and oligodendrocytes suggesting an interaction between at least two pathogenic mechanisms.

Amyloid beta-Protein Precursor↗
PubMed2000

Intraventricular infusion of apolipoprotein E ameliorates acute neuronal damage after global cerebral ischemia in mice.

The ability of intraventricular infusion of apolipoprotein E (apoE) to reduce neuronal damage after global cerebral ischemia was investigated in apoE-deficient and wild-type mice. ApoE (5 microg/mL lipid-conjugated derived from human plasma; 1 microL/h, continuous infusion) significantly reduced neuronal damage in the caudate nucleus and CA2 pyramidal cell layer by approximately 50% in apoE-deficient mice after global ischemia compared to vehicle infusion. In wild-type mice infused with apoE, there was a trend for ischemic neuronal damage to be reduced. ApoE-infused mice had a marked reduction in 4-hydroxynonenal immunoreactivity, as a marker of lipid peroxidation. The results show that the presence of apoE at or after the time of injury can be neuroprotective, possibly via an anti-oxidant mechanism.

Aldehydes↗
PubMed2000

The lipid peroxidation by-product 4-hydroxynonenal is toxic to axons and oligodendrocytes.

Lipid peroxidation and the cytotoxic by-product 4-hydroxynonenal (4-HNE) have been implicated in neuronal perikaryal damage. This study sought to determine whether 4-HNE was involved in white matter damage in vivo and in vitro. Immunohistochemical studies detected an increase in cellular and axonal 4-HNE within the ischemic region in the rat after a 24-hour period of permanent middle cerebral artery occlusion. Exogenous 4-HNE (3.2 nmol) was stereotaxically injected into the subcortical white matter of rats that were killed 24 hours later. Damaged axons detected by accumulation of beta-amyloid precursor protein (beta-APP) were observed transversing medially and laterally away from the injection site after intracerebral injection of 4-HNE. In contrast, in the vehicle-treated animals, axonal damage was restricted to an area immediately surrounding the injection site. Exogenous 4-HNE produced oligodendrocyte cell death in culture in a time-dependent and a concentration-dependent manner. After 4 hours, the highest concentration of 4-HNE (50 micromol/L) produced 100% oligodendrocyte cell death. Data indicate that lipid peroxidation and production of 4-HNE occurs in white matter after cerebral ischemia and the lipid peroxidation by-product 4-HNE is toxic to axons and oligodendrocytes.

Aldehydes↗
PubMed1999

Calpain activation and cytoskeletal protein breakdown in the corpus callosum of head-injured patients.

Calpain-mediated breakdown of the cytoskeleton has been proposed to contribute to brain damage resulting from head injury. We examined the corpus callosum from patients who died after a blunt head injury in order to determine if there was evidence of these pathophysiological events in a midline myelinated commissure that is susceptible to damage after human head injury. Western blotting revealed marked reductions in the levels of neurofilament triplet proteins 200 and 68kDa in the corpus callosum of head-injured patients compared with control subjects. Neurofilament 200kDa levels were significantly reduced as detected by either phosphorylation-dependent or -independent antibodies. In contrast, there were minimal changes in the levels of beta-tubulin or the microtubule-associated protein, tau, in the head-injured patients, although amyloid precursor protein immunostaining demonstrated axonal damage in 9 of the 10 patients. The inactive 800kDa and active 76kDa subunits of mu-calpain were present in control subjects and head-injured patients. However, there was a significant increase in the levels of calpain-mediated spectrin breakdown products in head-injured patients compared with the control subjects. The results demonstrate that following human blunt head injury, there is a significant degradation of neurofilament proteins and increased levels of calpain-mediated spectrin breakdown products within the corpus callosum. Therefore, our data support the hypothesis that calpain-mediated breakdown of the cytoskeleton may contribute to axonal damage after head injury.

Adult↗
PubMed1994

Mechanisms of recovery of swallow after supraglottic laryngectomy.

This study examines oropharyngeal swallow disorders and measures of pharyngeal and laryngeal movement during deglutition from videofluorographic studies of oropharyngeal swallow in 9 patients who had undergone supraglottic laryngectomy and 9 age-matched normal subjects. The swallows of surgical patients were examined at 2 weeks and 3 months postoperatively. Two critical factors in recovery of swallowing were identified: (a) airway closure at the laryngeal entrance, that is, the space between the arytenoid cartilage and the base of the tongue, and (b) the movement of the tongue base to make complete contact with the posterior pharyngeal wall. When patients achieved these two functions, they returned to normal swallowing. The duration of tongue base contact to the posterior pharyngeal wall and extent of anterior movement of the arytenoid increased significantly from 2 weeks to 3 months in the surgical patients. At 2 weeks postsurgery, patients who had undergone supraglottic laryngectomy exhibited significantly shorter airway closure and tongue base to pharyngeal wall contact, reduced laryngeal elevation, increased width of cricopharyngeal (CP) opening, and later onset of airway closure and tongue base movement than normal subjects. These significant differences remained at 3 months postoperatively, although swallow measures were moving toward normal in the patients who had undergone supraglottic laryngectomy. Comparison of patients not eating at 2 weeks with patients at the time of first eating revealed significantly longer duration of tongue base contact to the pharyngeal wall, longer duration of airway closure, and greater movement of the arytenoid in patients who were eating. Results indicate that the focus of swallowing therapy after supraglottic laryngectomy should be on improvement of posterior movement of the tongue base and anterior tilting of the arytenoid to close the airway entrance and improve bolus propulsion (in the case of the tongue base).

Barium Sulfate↗
PubMed1994

Detecting, preventing, and managing patients' alcohol problems.

OBJECTIVE: To examine Canadian family physicians' attitudes, beliefs, and practices regarding alcohol use and alcohol-related problems among their patients. DESIGN: A self-administered questionnaire mailed to a random sample of 2883 family physicians. The survey was conducted using a modified Dillman method. PARTICIPANTS: Canadian physicians in active office-based practice during 1989. Sample included certificated and noncertificated members of the College of Family Physicians of Canada, as well as non-members of the College. MAIN OUTCOME MEASURES: Perceived importance of various health-promotion behaviours; attitudes and beliefs about working with problem drinkers; current knowledge and practices regarding identifying and managing problem drinkers; and demographic characteristics. RESULTS: Respondents had a strong sense of role legitimacy in working with problem drinkers, but predominantly negative and pessimistic attitudes. Half the respondents felt they had failed in their work with problem drinkers. More physicians agreed on a psychosocial etiology for alcoholism than on a biological origin. Three quarters of respondents said they "almost always" ask patients about quantity and frequency of alcohol use, and just over one third "almost always" ask about problems related to drinking. Data also suggest doctors have relatively few patients with alcohol problems, and they need help in responding to such patients. CONCLUSION: Physicians need more training for their role in identifying and managing patients with alcohol problems.

Alcohol Drinking↗
PubMed1986

Peripheral plasma levels of prostaglandin metabolites, cortisol and prolactin in women undergoing falope ring application and tubal cautery.

The levels of 11-deoxy-13,14-dihydro-15-keto-11 beta, 16 xi-cyclo PGE2 (bicyclo PGEM), 13,14-dihydro-15-keto PGF 2 alpha (PGFM), cortisol and prolactin were measured by radioimmunoassays in five serial plasma samples collected from fourteen patients undergoing falope ring application and three patients undergoing tubal electrocautery. Bicyclo PGEM, PGFM and cortisol levels were unchanged regardless of the type of tubal occlusion procedure or the type of anesthesia administered (7 received general and 10 local anesthesia). Prolactin levels, on the other hand, markedly increased. The increase was greatest in women that received general anesthesia. The lack of change in bicyclo PGEM and PGFM in peripheral plasma would suggest a local transfer of PGs produced by injured tubal tissue to other parts of the tube and the uterus resulting in increased contractions and pelvic pain.

Dinoprost↗
PubMed1986

The patient-centred clinical method. 2. Definition and application.

In this article, the patient-centred clinical method is described in operational terms. Definitions are given for the patient's expectations, feelings and fears. The physician behaviours described are: facilitations, acknowledgements, cut-offs and returns. Using the definitions, a method was devised for scoring video-taped interviews for the degree of 'patient-centredness'. The method proved to have good inter-observer reliability.

Attitude to Health↗
PubMed1986

The patient-centred clinical method. 3. Changes in residents' performance over two months of training.

A method for assessing the patient-centred approach was used to identify changes taking place in the interviewing behaviour of 13 residents during two months in a teaching practice. The descriptive study confirmed the prediction that the residents' approach would become more patient-centred. A statistically significant change from August to October was found in the number of facilitating behaviours shown by residents (P less than 0.05) and there was a change in the number of fears expressed by patients (P less than 0.10). Increases in the number of expectations, feelings and prompts were noted but were not significant. The frequency with which residents cut off patients' expressions increased on the whole, although not significantly. The findings suggest that while these residents had succeeded in increasing their facilitating behaviours over two months (one-sixth of their family medicine experience) they had not yet found ways of responding to the many problems elicited.

Family Practice↗