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Biomedical subjects

K M Welch

Publications and source records attributed to K M Welch.

At least 109 records · Page 6Linked to original sources
PubMed1991

Platelet glycine, glutamate and aspartate in primary headache.

Platelet levels of glutamic and aspartic acid and glycine were measured in patients with migraine with aura, migraine without aura, tension headache and cluster headache. High levels of these amino acids were found in patients with migraine with aura compared to normal subjects and other headache groups. During headache, glutamate levels further increased in migraine with aura patients. These findings may have relevance to the neurological symptoms of migraine with aura.

Aspartic Acid↗
PubMed1991

Cerebral blood flow and neuropsychological asymmetries in unilateral stroke.

BACKGROUND AND PURPOSE: This study sought to determine the degree of agreement between asymmetries of neuropsychological functioning and nine methods of quantifying asymmetries of regional cerebral blood flow. METHODS: The regional cerebral blood flow methods combined three markers of cerebral blood flow asymmetry (percent hemispheric difference, maximum percent probe-pair asymmetry, and number of probe-pair asymmetries) with three indexes of regional cerebral blood flow (fast compartment flow, initial slope index, and initial slope). Eleven patients with left hemispheric ischemic strokes and 13 with right hemispheric ischemic strokes were studied with the xenon-133 inhalation technique and neuropsychological tests. RESULTS: Blind clinical judgments of neuropsychological asymmetry significantly correlated with all nine methods of cerebral blood flow asymmetry determination; correlations ranged from -0.42 to -0.77. Clinical judgment of asymmetry of neuropsychological functioning accurately predicted the hemisphere of lower flow in 71-92% of cases, depending on the method of cerebral blood flow asymmetry determination. Agreement between cerebral blood flow and neurobehavioral signs of asymmetry was greater for initial slope and initial slope index than for the fast flow index. The initial slope and initial slope index showed equally good agreement. The use of the number of asymmetrical probe pairs to detect cerebral blood flow asymmetries agreed less well with neurobehavioral asymmetry than did the other two markers studied. CONCLUSIONS: Both the initial slope index and the initial slope measures of cerebral blood flow are useful in predicting neuropsychological asymmetries, especially when the magnitude of the asymmetry is taken into account.

Cerebrovascular Circulation↗
PubMed1991

Platelet secretory products may contribute to neuronal injury.

BACKGROUND: We do not fully understand the mechanisms for neuronal damage following cerebral arterial occlusion by a thrombus that consists mainly of platelets. The view that certain endogenous substances, such as glutamate, may also contribute to neuronal injury is now reasonably well established. Blood platelets are known to contain and secrete a number of substances that have been associated with neuronal dysfunction. Therefore, we hypothesize that a high concentration (approximately several thousand-fold higher than in plasma, in our estimation) of locally released platelet secretory products derived from the causative thrombus may contribute to neuronal injury and promote reactive gliosis. SUMMARY OF COMMENT: We have recently been able to report some direct support for this concept. When organotypic spinal cord cultures were exposed to platelet and platelet products, a significant reduction in the number and the size of the surviving neurons occurred in comparison with those in controls. We further observed that serotonin, a major platelet product, has neurotoxic properties. There may be other platelet components with similar effect. CONCLUSIONS: The hypothesis of platelet-mediated neurotoxicity gains some support from these recent in vitro findings. The concept could provide a new area of research in stroke, both at the clinical and basic levels.

Animals↗
PubMed1991

Nuclear magnetic resonance spectroscopy study of human brain after cardiac resuscitation.

We used 31P nuclear magnetic resonance spectroscopy to study the cerebral metabolic function of eight patients with severe postischemic anoxic encephalopathy secondary to cardiac arrest. Spectroscopy was performed at 18 +/- 13 and 64 +/- 20 hours after resuscitation. Glasgow Coma Scale scores at the time of initial and repeat spectroscopy were 3.6 +/- 1.2 and 3.5 +/- 1.2, respectively. In those patients whose spectra were of adequate quality to monitor pH, all demonstrated tissue alkalosis in at least one brain region. The mean brain pH at initial spectroscopy was 7.14 +/- 0.09 and was significantly alkalotic when compared with age- and sex-matched normal controls (pH = 6.98 +/- 0.04, p less than 0.0001). Five of the eight patients showed at least one region of persistent alkalosis at repeat spectroscopy, whereas one patient demonstrated severe acidosis with a pH of 6.42. Spectra demonstrated marked metabolic heterogeneity, ranging from normal in appearance to complete obliteration of all high-energy phosphates with only inorganic phosphate remaining.

Aged↗
PubMed1991

Assessing the effects of antihypertensive medication on cerebral blood flow: demonstration in internal carotid artery occlusion.

Dynamic cerebral blood flow (CBF) studies using acetazolamide or hypercapnia as a vasodilatory challenge have attempted to evaluate intracranial hemodynamics. We report two patients with asymptomatic internal carotid artery occlusion in whom the vasodilatory stimulus was a single oral dose of antihypertensive medication (prazosin hydrochloride or enalapril maleate). In both patients, changes in regional CBF occurred that were larger than those seen in nine normal controls. One patient experienced an improvement in regional CBF with a reduction in probe pair asymmetry. In the other patient, who had bilateral carotid artery disease, a decrease in regional CBF in all 16 probes (mean decrease 12 percent) and an accentuation of the predose asymmetry were observed. Both patients remained asymptomatic throughout the study. Assessing these effects on cerebral circulation may help identify patients at risk for iatrogenic focal cerebral ischemia and provide information regarding the functional status of the cerebral vasculature.

Aged↗
PubMed1991

Accelerated intracranial occlusive disease, oral contraceptives, and cigarette use.

We report clinical and angiographic features of accelerated intracranial occlusive disease resembling moyamoya vasculopathy in five young women who used oral contraceptives (OCs) and smoked cigarettes, but generally had no other obvious risk factors for cerebrovascular disease. Three women had been on OCs for at least 4 years, one woman each had been on OCs for 3 months and for 2 weeks. All five women had smoked cigarettes for at least eight pack-years. Intermittent and progressive multifocal cognitive, visual, motor, or sensory hemispheric symptoms and signs developed in all. All patients developed strokes, four preceded by transient ischemic attacks. Cerebral angiography demonstrated bilateral supraclinoid internal carotid artery stenosis in four patients and proximal posterior cerebral artery stenosis in one. Additional features included rete mirabile, telangiectasias, prominent lenticulostriate collaterals, and multifocal distal cerebral branch occlusions. Three had mild abnormalities of serum fibrinogen, antinuclear antibody, erythrocyte sedimentation rate, or CSF IgG. After discontinuing OCs and reducing cigarette use, four women have not had further strokes over a mean follow-up of approximately 5 years. In certain young women, clinical and angiographic features resembling moyamoya may develop with the use of OCs and cigarettes. We speculate that an immunologically mediated vasculopathy may explain, in part, this unusual cerebrovascular syndrome in otherwise healthy young women.

Adult↗
PubMed1991

Effect of mild hyperthermia on the ischemic infarct volume after middle cerebral artery occlusion in the rat.

We investigated the effect of mild whole-body hyperthermia (40 degrees C) on a permanent middle cerebral artery occlusion (MCAo) model in Fisher rats by subjecting them to MCAo under the following conditions: (1) normothermia (n = 20); (2) hyperthermia (n = 14) before (1 hour), during, and after (1 hour) MCAo; and (3) post-MCAo hyperthermia (n = 14) for 1 hour. We measured brain and body temperatures during the experiment using micro-thermocouples and blood-brain-barrier (BBB) permeability using Evans blue staining of the brain. We measured the volume of the infarcted brain tissue 4 days after MCAo. We detected no differences in BBB permeability among three groups. The volume of infarcted tissue was significantly greater (p less than 0.05) for the two groups of hyperthermic animals than the normothermic animals. Our data suggest that mild hyperthermia, both during and after induction of ischemia, has a detrimental effect on the ischemic infarct volume in this model.

Animals↗
PubMed1991

A comparative study of the cerebrovascular complications of cocaine: alkaloidal versus hydrochloride--a review.

Cocaine, especially in its alkaloidal or "crack" form, has been increasingly associated with cerebrovascular disease. Before the crack epidemic, cocaine hydrochloride (HCl) was also implicated as a cause of stroke. However, less is known about the differences in stroke subtypes, age at stroke onset, or presence of underlying structural cerebrovascular disease with different forms of cocaine use. We compared 26 patients (previously reported) from our four institutions plus 16 cases reported in the literature of stroke associated with alkaloidal cocaine to 63 (57 reported in the literature and six not previously reported from our four institutions) cases of stroke associated with cocaine HCl. Ischemic and hemorrhagic strokes are equally likely after alkaloidal cocaine use, whereas cocaine HCl is more likely (approximately 80% of the time) to cause hemorrhagic stroke, with approximately half the intracranial hemorrhages occurring from ruptured cerebral saccular aneurysms or vascular malformations. The presence of an underlying cerebral aneurysm was more common among patients with cocaine HCl-associated strokes than alkaloidal cocaine-associated strokes. Cerebral infarction was significantly more common among the alkaloidal cocaine users than in all the cocaine HCl users, and this was also true when alkaloidal cocaine users were compared with parenteral cocaine HCl (intravenous and intramuscular) users. Only hemorrhagic stroke has been reported with intravenous cocaine HCl use. We conclude that the pathogenesis of cocaine-related stroke is heterogeneous, and depends, in part, on the form of cocaine used.

Administration, Intranasal↗
PubMed1991

[Effect of chronic antiplatelet treatment on platelet activating factor-induced platelet activity in stroke].

The effect of chronic antiplatelet treatment on PAF--induced platelet aggregation, ATP--release, and cytoplasmic ionized calcium was studied in 20 acute ischemic stroke patients. Chronic antiplatelet treatment failed to suppress these PAF--induced platelet responses. We speculate that selective PAF antagonists may be useful in suppressing PAF--induced platelet activation, and thereby possibly improve the treatment of stroke.

Adenosine Triphosphate↗
PubMed1990

Time course of postischemic intracellular alkalosis reflects the duration of ischemia.

We investigated the long-term (up to 1 week) relationships between the duration of cerebral ischemia and postischemic energy metabolic profile, pH, and tissue edema in the rat. Ten rats each were subjected to 8 or 12 min of forebrain ischemia induced by bicarotid occlusion concurrent with systemic hypotension, and the results were compared with those of 10 sham-operated rat controls. In vivo 31P nuclear magnetic resonance spectroscopy was performed prior to ischemia and at intervals up to 168 h after ischemia. Cerebral edema (measured by specific gravity) was assessed prior to ischemia and at 24, 72, and 168 h after ischemia. The data revealed significant differences in the brain tissue pH profile over time between the ischemic groups (p less than 0.03). The 12-min ischemic animals exhibited brain tissue alkalosis (pH = 7.27 +/- 0.12) at 24 h compared with both sham (pH = 7.09 +/- 0.08) at 24 h and preischemic (pH = 7.06 +/- 0.04) pH values. The pH remained alkalotic (pH = 7.23 +/- 0.15) through the 48-h time period. In contrast, in the 8-min group, the onset of alkalosis was delayed until 48 h after ischemia (pH = 7.24 +/- 0.15), and pH remained alkalotic for only 24 h. No difference in high-energy phosphate metabolism was detected between groups. A different time dependence of tissue pH and specific gravity changes after 12 min of ischemia was detected. The present study suggests that the duration of an ischemic event marks the time of onset of brain tissue alkalosis and its duration and that cerebral edema alone cannot explain the pH changes.

Alkalosis↗
PubMed1990

Characterization of cerebral energetics and brain pH by 31P spectroscopy after graded canine cardiac arrest and bypass reperfusion.

Recovery of cerebral energy metabolism is used to indicate CNS viability after ischemia. This study utilized 31P nuclear magnetic resonance (NMR) spectroscopy to measure cerebral energy state and intracellular pH in dogs subjected to 8, 12, or 16 min of cardiac arrest and reperfusion using cardiopulmonary bypass. Spectra were obtained throughout ischemia and initial reperfusion and repeated at 30 and 144 h post ischemia. Neurologic deficit scoring was performed at 12 and 24 h post insult and then daily. High-energy phosphates were depleted by the end of all ischemic intervals. Recovery occurred within 60 min of reperfusion and persisted with no differences in the rate of return between groups (p greater than 0.05). Brain pH (pHb) decreased by the end of ischemia in all groups (p less than 0.0001). Neither the pHb nadir nor its recovery differed between groups (p greater than 0.05). Although longterm neurologic outcome differed between groups, the spectra were similar. Assessment of cerebral energy state using 31P NMR spectroscopy does not appear to be a sensitive indicator of neurologic outcome after global ischemia in dogs. Return of high-energy phosphates may be a necessary but not sufficient condition for cerebral recovery after ischemia. The return of high-energy phosphates after a 16-min cardiac arrest, however, indicates a potential for neurological recovery.

Acid-Base Equilibrium↗
PubMed1990

Ovarian steroid levels in migraine with and without aura.

Radioimmunoassays were used to measure interictal levels of ovarian steroids (oestradiol, total oestrogens and progesterone) in migraine patients at the onset of menses and coincident with the luteinizing hormone surge preceding ovulation. Results of these verified biochemically-contrasting points of the ovarian cycle were used to compare 13 migraine patients without aura and 6 migraine patients with aura with 17 non-migraine women. No group differences were found for physiological basal levels of ovarian steroids measured at menses. Preceding ovulation elevation in oestradiol levels relative to normal was found in migraine patients with aura but not in migraine patients without aura. These results suggest that a variation in oestradiol levels is an important factor in the different clinical expressions of migraine.

Estradiol↗
PubMed1990

Neuromagnetic fields in migraine: preliminary findings.

Neuromagnetic signals consistent with spreading cortical depression have been observed in 9 of 12 migraine patients studied, but not in normal controls (out of 8 studied) or in patients with non-migrainous headache (4 studied). These signals consist of large amplitude, usually biphasic waveforms presumably arising from the onset or offset of spreading cortical depression in a sulcus, and prolonged attenuation of magnetic amplitudes, associated with suppressed neuronal activity. Techniques are described which recognize various kinds of artefacts and which distinguish changes in state of arousal of the patient from the presumed spreading cortical depression signals.

Cortical Spreading Depression↗
PubMed1990

Event-related slow potentials and associated catecholamine function in migraine.

Plasma norepinephrine and dopamine and event-related slow potentials were measured at menses and ovulation in migraine with and without aura relative to normal subjects. The results indicated that at menses, but not ovulation, plasma dopamine was increased and norepinephrine was decreased relative to normal. This catecholamine imbalance was greater in migraine without aura than in migraine with aura. Conversely, event-related slow potentials measured over the posterior cortex at ovulation but not at the menses was altered relative to normal. Early epoch negativity was reduced in migraine with aura, whereas late epoch negativity was reduced in migraine without aura. The results suggested that (a) migraine without aura may involve dynamic shifts in the function of both norepinephrine and dopamine responsive neurons; (b) pathophysiology of migraine with aura is less dependent on catecholamine imbalance (norepinephrine alone affected); (c) these pathophysiological mechanisms are most prevalent in or restricted to posterior cortical regions but may be modulated by brainstem mechanisms.

Adult↗
PubMed1990

Cerebral control of directed visual attention and orienting saccades.

The object of this experiment was to identify the contribution of the frontal and parietal lobes to the control of visual attention and voluntary saccades. A symbolic spatial cue (arrow) was used to indicate validly or invalidly the location of a visual target located to the left or right of the cue. Manual reaction time and reaction time to initiate a saccade to the target were measured. Patients with damage to the left frontal lobe (n = 6), right frontal lobe (n = 7) and right parietal lobe (n = 7) were compared with normal control subjects (n = 20). A sex difference was found for the right cerebral hemisphere patients in the manual reaction time data. Right parietal males and right frontal females showed an overall elevation in manual reaction time, reflecting an inability to maintain a normal level of visual arousal and/or motor activation. Conversely, right frontal males and right parietal females were not influenced significantly by cue validity, suggesting that they were unable to direct visual attention in a covert manner. All subjects showed a normal effect of cue validity on saccade reaction time. Thus the cortical areas studied do not appear to be necessary for directing visual attention with a saccade. Cue validity, however, affected saccade amplitude, especially in the left visual field of patients with right hemisphere damage. The cue validity effect depended both on the sex of the subject and the anterior/posterior location of damage in the right hemisphere. Damage to the right frontal lobe resulted in an 'under' reaction to the spatial cues, especially in the male patients. Saccades were smaller than normal following the valid cues, but larger than normal following the invalid cues. The effect was opposite following damage to the right parietal lobe. In this case, saccade amplitude reflected an 'over' reaction to the spatial cues, especially in the female patients. Saccades were larger than normal following valid cues and smaller than normal following invalid cues.

Analysis of Variance↗