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Biomedical subjects

W Young

Publications and source records attributed to W Young.

At least 145 records · Page 8Linked to original sources
PubMed1987

The post-injury responses in trauma and ischemia: secondary injury or protective mechanisms?

Transient injuries to the central nervous system, whether due to trauma or ischemia, often produce long lasting metabolic derangements, lipid peroxidation, edema, and falls in blood flow at the lesion site. Because these post-injury responses are believed to be causes of secondary injury, much research effort has been devoted to developing therapies that prevent them. Recent studies suggest that excessive Ca entry into injured cells instigates these post-injury responses. A new theory is proposed to explain these post-injury responses. This theory posits that Ca ions entering dying cells activate phospholipases that break down membranes to release phosphates. The phosphates then bind and precipitate Ca ions, producing the profound and prolonged decreases in extracellular Ca activity that have been observed in traumatized spinal cords and ischemic brains. The phospholipase activity also facilitates release of lipid peroxides which enhance edema and reduce blood flow. Both of these in turn decrease Ca diffusion to the lesion site and slow the recovery of extracellular Ca activity, giving the tissue time to recover and avoiding the consequences of rapid restoration of extracellular Ca activity. The theory suggests that central nervous tissues evolved these Ca-activated responses as a general mechanism to protect neurons against excessive Ca entry. Brain and spinal cord tissues contain very high concentrations of phosphates, many times greater than is necessary to bind all the Ca ions in the tissues. This excessive Ca buffering capacity enables the tissue to sacrifice a small proportion of severely injured cells to reduce Ca entry into less severely injured neurons. This process will also rapidly eliminate moribund cells that may otherwise linger and consume oxygen and metabolic substrates better utilized by the remaining cells. If confirmed, this theory raises serious questions concerning the current experimental therapeutic approaches to CNS trauma and stroke. Therapy should perhaps be designed to optimize rather than to abort the post-injury responses.

Animals↗
PubMed1987

Total phosphate determination in brain tissues: a method for regional determination of total phosphate in rat brain.

A quantitative microassay method is described for brain tissue phosphates. Based on molybdate colorimetric measurements of inorganic phosphate in tissue solutions prepared by acid digestion and high temperature ashing, the method includes the use of calcium to precipitate inorganic phosphate in acid-digested tissues and a correction for contaminants released from porcelain crucibles during the ashing procedure. This method was used to measure the total tissue phosphate concentrations in regional microsamples of rat brain. Averaged values derived from these regional measurements were 100.1 +/- 10.2 mumol/gm wet tissue weight, corresponding closely to whole brain tissue phosphate values reported in the literature. Phosphate concentrations were remarkably uniform in different areas of the cortex and basal ganglia.

Animals↗
PubMed1987

Failure of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) to inhibit cell-cell coupling in newborn mouse epidermal cells and Chinese hamster V79 cells under non-standard culture conditions.

The function of the skin tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) during two-stage carcinogenesis in mice remains obscure because of TPA's numerous phenotypic effects. In vitro studies under established conditions have generated substantial interest in TPA's ability to inhibit, although transiently in some cases, direct cell-cell coupling in several permanent cell lines, by analogy allowing latent 'initiated cells' to escape homeostatic controls in vivo. Using different culture conditions designed to improve the growth of newborn mouse epidermal cells, we examined dye coupling in these cells, and metabolic co-operation in V79 cells, finding no effect of TPA on coupling. It appears that this effect of TPA is overly sensitive to in vitro conditions. Since a corresponding physiological effect has not yet been demonstrated in vivo, future studies should be directed to establish that coupling inhibition by TPA actually does occur and plays some role during tumor promotion in vivo, and is not merely a characteristic of certain culture systems.

Animals↗
PubMed1986

Potassium and calcium changes in injured spinal cords.

In previous studies, we found large rises in extracellular potassium activity ([K+]e) and falls in extracellular Ca2+ activity ([Ca2+]e) in injured spinal cords. [K+]e recovered rapidly at the impact site within 2 h but ischemia onset at 2-3 h paradoxically did not cause further [K+]e rises. [Ca2+]e, in contrast, remained depressed for long periods of time, suggesting either an effective block of Ca diffusion to the injury site or a deep Ca2+ sink at the impact site. To resolve questions raised by the [K+]e and [Ca2+]e recovery patterns, we used atomic absorption spectroscopy to measure spatial distributions of tissue concentrations of K ([K]t) and Ca ([Ca]t) in cat spinal cords injured by a standardized contusion, compared with uninjured controls. At the impact site, [K]t fell to 51% and 35% of control at 1 and 3 h. The K content of cord surrounding the impact site did not change significantly at 1 h, but K gains in surrounding cord at 3 h approximated K losses from the impact site. The K results indicate that contusion disrupts greater than 80% of cells at the impact site with K loss to adjacent cord, blood, and cerebrospinal fluid. Such losses may explain why subsequent ischemia at the impact site did not cause [K+]e rises. [Ca]t at the impact site increased to 37% and 59% above control at 1 and 3 h. The Ca gain at the impact site exceeded the amount of free extracellular Ca2+ available before injury within 2 cm of the impact site. At 1 h, the Ca lost in cord surrounding the impact site approximated the Ca gain at the impact site. These findings indicate that Ca accumulated at the impact site comes largely from surrounding cord. We propose that Ca sequestration by inorganic phosphates causes a deep Ca sink at the impact site.

Animals↗
PubMed1986

Balance reactions and eye-hand coordination in idiopathic scoliosis.

We undertook this study to determine if subclinical postural control mechanisms were abnormal in idiopathic scoliosis. Ninety-one female patients and fifty-seven age-matched female controls were examined. We used a force plate ataxiometer to quantitate postural sway in the standing position and recorded the displacement and acceleration of the center of pressure during static stance and under perturbation with eyes opened and closed. A joystick-controlled video system was used to measure reaction time and eye-hand motor coordination. The scoliosis group demonstrated significantly less sway during two of the eight standing balance conditions and on the remaining balance tests there was a similar trend, albeit nonsignificant. The reaction time for the scoliosis group was also significantly slower, but the accuracy was not significantly worse. We noted no statistical differences between progressive and nonprogressive or between braced and unbraced patients. The subgroup of patients whose curves progressed despite bracing had a tendency to demonstrate greater stability on all standing tests. They also exhibited faster reaction times and less error in eye-hand coordination than other patient groups. No correlation existed between severity of curve and test performance. We found no indication of deficient balance in idiopathic scoliosis, and the tests could not predict curve progression.

Adolescent↗
PubMed1986

Tissue Na, K, and Ca changes in regional cerebral ischemia: their measurement and interpretation.

A simple and reliable method of quantifying tissue damage is described. This method, based on atomic absorption spectroscopic determinations of Na, K, and Ca concentrations in small brain samples, was applied to the rat middle cerebral artery occlusion model (MCAo). At the infarct site by 24 hours, Na concentration more than doubled, Ca concentration increased by greater than 70%, and K concentration fell nearly 80%; these changes are consistent with a greater than 80% disruption of cells. A remarkable acceleration of ionic shifts occurred between 4 and 6 hours after MCAo. At 4 hours, only 20-30% of the ionic shifts found at 24 hours had occurred; by 6 hours, 80-100% of the ionic shifts found at 24 hours had taken place. Since the measurements reflect ionic movement into and out of the tissue, they are likely to represent irreversible tissue damage. Although blood brain barrier breakdown may have contributed to an increased rate of ionic shifts, large ionic gradients must have been present between the extracellular space and the vascular compartment at 4-6 hours to drive the ionic shifts. Our results suggest an upper time limit of 4 hours for treatments of acute ischemic tissue damage in the rat MCAo model. The methods and analytical approach described may be useful for determining the time window for therapeutic intervention in acute CNS injuries, as well as for evaluating treatment effects.

Acute Disease↗
PubMed1986

Ca paradox in neural injury: a hypothesis.

The deleterious effects of Ca ionic entry into neurons has been speculated to be a final common pathway of cell death. However, a direct cause-effect relationship between Ca and neuronal death has been difficult to establish. Cells dying from any cause will accumulate Ca. The entry of Ca into neurons and the subsequent pathological changes associated with Ca entry consequently may be manifestations rather than causes of cell death. Recent work showing that extracellular Ca ionic activity becomes profoundly depressed in injured spinal cord and ischemic cerebral cortex prompted a new hypothesis on Ca mediated damage. We propose that the initial fall in extracellular Ca activity, resulting from the death of some cells in the tissue, increases the susceptibility of the surviving cells to Ca entry when extracellular Ca activity levels normalize and that this accounts for part of the secondary damage that has been observed in neural injury models. Such a phenomenon has been described in cardiac tissues. Dubbed Ca paradox, this phenomenon occurs when heart cells are perfused with Ca-free solutions for several minutes followed by the return to normal Ca-containing solutions. The cardiac cells die and undergo physiological, morphological, biochemical, and other changes. The evidence supporting a Ca paradox phenomenon in injured neural tissues is summarized. The therapeutic implications of Ca paradox in neural tissue injury are discussed.

Animals↗
PubMed1986

Common components of industrial metal-working fluids as sources of carbon for bacterial growth.

Water-based metal-working fluids used in large-scale industrial operations consist of many components, but in the most commonly used formulations only three classes of components are present in high enough concentrations that they could, in principle, provide enough carbon to support the high bacterial densities (10 CFU/ml) often observed in contaminated factory fluids. These components are petroleum oil (1 to 5%), petroleum sulfonates (0.1 to 0.5%), and fatty acids (less than 0.1%, mainly linoleic and oleic acids supplied as tall oils). We isolated pure strains of predominating bacteria from contaminated reservoirs of two metal-working systems and randomly selected 12 strains which we tested in liquid culture for growth with each of the metal-working fluid components as the sole source of carbon. Of the 12 strains, 7 reached high density (10 CFU/ml from an initial inoculum of less than 2 x 10) in 24 h, and 1 strain did the same in 48 h with 0.05% oleic or linoleic acid as the carbon source. These same strains also grew on 1% naphthenic petroleum oil but required up to 72 h to reach densities near 10 CFU/ml. One strain grew slightly and the others not at all on the petroleum sulfonates. The four remaining strains did not grow on any of the components, even though they were among the predominating bacteria in the contaminated system. Of the seven strains that grew best on the fatty acids and on the naphthenic petroleum oil, five were tentatively identified as Acinetobacter species and two were identified as Pseudomonas species. Four of the bacteria that did not grow were tentatively identified as species of Pseudomonas, and one could not be identified.

Journal Article↗
PubMed1985

A phase I trial of naloxone treatment in acute spinal cord injury.

Results of a Phase I trial of the opiate antagonist naloxone for treatment of patients with acute spinal cord injury are reported. Naloxone was administered in doses ranging from 5 to 200 mg/sq m (0.14 to 5.4 mg/kg) for up to 48 hours. The patients ranged in age from 16 to 79 years (mean 37 years). Twenty patients received naloxone as a loading dose of 5 to 50 mg/sq m (0.14 to 1.43 mg/kg), followed by a maintenance dose of 20% of the loading dose given as a continuous infusion hourly for 47 hours (Group 1). Nine patients received a loading dose of 100 to 200 mg/sq m (2.7 to 5.4 mg/kg) and a maintenance dose of 75% of the initial dose hourly for 23 hours (Group 2). These higher doses (2.7 to 5.4 mg/kg) have been found to be effective in experimental spinal cord injury. Neurological examinations were performed and somatosensory evoked potentials (SEP's) were obtained as soon after admission as possible and again 1, 2, 3, and 7 days, 3 weeks, and 6 weeks to 6 months after admission. The 20 Group 1 patients who received 1.43 mg/kg or less of naloxone showed no improvement in neurological status or SEP's. All but three (15%) of these patients had a complete neurological deficit at the time of admission. Treatment was begun an average of 12.9 hours after injury. Among the nine Group 2 patients treated with 2.7 mg/kg or more, there were five patients (56%) with incomplete deficits. This group received naloxone an average of 6.6 hours after admission. Two of the five Group 2 patients with incomplete lesions showed improvement in their neurological condition and/or SEP's within 36 hours of receiving the drug. One of the four Group 2 patients with a complete lesion at the time of admission was able to localize pressure sensation in his legs 36 hours after completion of the drug infusion. Four Group 2 patients (two with complete and two with incomplete lesions) have shown improvement in their SEP's, suggesting recovery of SEP's in a dose-related fashion. Four patients experienced increased pain after administration of the loading dose and during the maintenance infusion; in only one patient was this severe enough to require discontinuation of the drug. Of the 29 patients treated with naloxone, four died within 6 weeks of admission, for a mortality rate of 13.8%.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1984

Somatosensory evoked potentials (SEPs) and cortical single unit responses elicited by mechanical tactile stimuli in awake monkeys.

The origins of surface recorded evoked potentials have been investigated by combining recordings of single unit responses and somatosensory evoked potentials (SEPs) from the postcentral gyrus of 4 alert macaque monkeys. Responses were elicited by mechanical tactile stimuli (airpuffs) which selectively activate rapidly adapting cutaneous mechanoreceptors, and permit patterned stimulation of a restricted area of skin. Epidurally recorded SEPs consisted of an early positive complex, beginning 8-10 msec after airpuff onset, with two prominent positive peaks (P15 and P25), succeeded by a large negative potential (N43) lasting 30 msec, and a late slow positivity (P70). SEPs, while consistent in wave form, varied slightly between monkeys. The amplitude of the early positive complex was enhanced by increasing the number of stimulated points, or by placing the airpuffs in the receptive fields of cortical neurons located beneath the SEP recording electrode. SEP amplitude was depressed when preceded 20-40 msec earlier by a conditioning stimulus to the same skin area. Single unit responses in areas 3b and 1 of primary somatosensory (SI) cortex consisted of a burst of impulses, beginning 11-12 msec after the airpuff onset, and lasting another 15-20 msec. Peak unitary activity occurred at 12-15 msec, corresponding to the P15 wave in the SEP. No peak in SI unit responses occurred in conjunction with the P25 wave. Although SI neurons fired at lower rates during P25, the lack of any peak in SI unit responses suggests that activity in other cortical areas, such as SII cortex, contributes to this wave. Most unit activity in SI cortex ceased by the onset of N43, and was replaced by a period of profound response depression, in which unit responses to additional tactile stimuli were reduced. We propose that the N43 wave reflects IPSPs in cortical neurons previously depolarized and excited by the airpuff stimulus. Late positive potentials (P70) in the SEP had no apparent counterpart in SI unit activity, suggesting generation at other cortical loci.

Animals↗
PubMed1984

The vestibulospinal free fall response: a test of descending function in spinal-injured cats.

A major problem in spinal cord injury research is quantification of motor function in animals. Most investigators in the field currently use neurologic scoring systems, relying on subjective observations of complex behaviours and assigning scores based on arbitrary criteria. These scoring scales are prone to observer bias and are nonspecific. We describe here a simple, reproducible, noninvasive, and objective test of a limited aspect of spinal motor function in cats, based on a well-known involuntary response of animals to sudden free fall. Free fall responses, or FFRs, have been studied in many species, including man, and are thought to be carried in ventral and lateral column pathways, i.e., vestibulospinal, reticulospinal, and rubrospinal tracts. We recorded the FFRs from hind and forelimb muscles of 100 cats before and after thoracic spinal cord injury. Hindlimb FFRs were shown to have three quantifiable components: a fast synchronous activation (E1) followed by a short silent period during which spinal segmental reflexes are inhibited (I1) and a late desynchronized excitatory burst (E2). Thoracic spinal injury produced hindlimb FFR losses ranging from greatly reduced amplitude to complete absence of response. Residual FFRs correlated with the extent of ventral column preservation and locomotory ability. Individual FFR components can be preserved. For example, some injured cats exhibited only 11 responses. Our work suggests that FFRs are a reliable and sensitive test of motor recovery in spinal cord injury.

Animals↗
PubMed1984

Somatosensory evoked potentials during spinal angiography and therapeutic transvascular embolization.

Somatosensory evoked potentials (SEP's) were monitored during 42 angiographic examinations and 33 therapeutic embolization procedures in 41 patients. The SEP amplitude decreased in 36 of the 42 angiographic techniques, but recovered to baseline within 2 to 4 minutes in all but one case. Angiographic opacification of the anterior spinal artery reduced SEP amplitude in all but two patients, who had lost their proprioceptive sense and had no recognizable SEP prior to the procedure. No neurological complications resulted from any of the angiography procedures. Of the 33 embolizations, 15 were performed in 12 patients with arteriovenous malformations (AVM's) and 18 in 17 patients with spinal canal tumors. There was only one complication associated with embolization: that occurred in a patient with an intramedullary spinal cord AVM. Monitoring SEP amplitude in this series of patients provided a means of rapidly and reliably identifying the anterior spinal artery, served to assess the potential risk of contemplated steps in embolization, and aided in the execution of the angiographic procedures.

Angiography↗