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Biomedical subjects

H R Winn

Publications and source records attributed to H R Winn.

At least 163 records · Page 9Linked to original sources
PubMed1990

Transcranial Doppler in cerebral vasospasm.

Transcranial Doppler provides a noninvasive method for recording blood flow velocity (and indirectly, diameter) in the basal cerebral arteries and therefore is especially useful in detecting vasospasm following subarachnoid hemorrhage. Vasospasm most commonly involves the basal arteries, where the changes in vessel diameter will be inversely proportional to the mean velocity measurements. Examination of patients requires that the examiner be experienced and familiar with the vascular anatomy and the various TCD indicators of vasospasm. Normal mean velocity for the MCA is 62 +/- 12 cm/sec. Significant spasm on angiogram of the MCA corresponds to a mean velocity of 120 cm/sec. Mean velocities of the MCA of 200 cm/sec or greater indicate severe spasm and correlate with 50% or greater narrowing on angiogram. Cerebral blood flow changes that can occur after subarachnoid hemorrhage and as a result of vasospasm may affect velocity values. A simultaneous index of CBF with either direct flow measurement techniques or by recording extracranial carotid artery velocity measurements may be helpful in reflecting these changes. Knowledge of the time course of the development and resolution of vasospasm using TCD can help the clinician predict which patients are at higher and lower risk of developing ischemic deficits, thereby guiding treatment. Several features of TCD assessment of vasospasm are similar to angiography. High TCD velocities, like severe angiographic vasospasm, are associated with delayed ischemic deficits and infarction, although some patients can remain asymptomatic despite these changes. Delayed ischemic deficits or infarctions in patients following subarachnoid hemorrhage usually will be preceded by markedly elevated velocity or other indicators of severe vasospasm.

Blood Flow Velocity↗
PubMed1990

Distribution of angiographic vasospasm after subarachnoid hemorrhage: implications for diagnosis by transcranial Doppler ultrasonography.

A study was undertaken to determine how frequently angiographic vasospasm occurs outside the normal access range of transcranial Doppler ultrasound in patients who have suffered a subarachnoid hemorrhage. Vasospasm located in the basal vessels is readily identifiable using transcranial Doppler ultrasound whereas spasm affecting the more distal, vertically oriented arteries is outside the standard detection range. It is therefore speculated that the sensitivity of the technique would be adversely affected by a high incidence of distal vasospasm. A total of 136 angiograms performed on 68 patients after a subarachnoid hemorrhage from anterior circulation aneurysms were reviewed to determine the typical distribution of vasospasm. Of the 40 cases that showed greater than or equal to 25% vessel narrowing, 50.0% had spasm restricted to the basal vessels, 42.5% had spasm involving both basal and distal segments, and 7.5% had spasm of the distal segments only. None of the patients with distal vasospasm alone developed delayed ischemic deficits. It is concluded that most patients with anterior circulation aneurysms who develop vasospasm will have involvement of the basal vessels, but a small number of patients may develop vasospasm only in distal vessels.

Adolescent↗
PubMed1989

Effect of inosine on pial arterioles: potentiation of adenosine-induced vasodilation.

We examined the cerebral vasoactivity of inosine and its effect on pial arteriolar vasodilation induced by adenosine. Pial circulation was observed through cranial windows implanted in rats anesthetized with halothane. No significant change in venous or arteriolar diameter was apparent when inosine (10(-6) to 10(-3) M) was superfused. In contrast, adenosine in concentrations of 10(-7) and 10(-6) M dilated pial arterioles by 9.0 +/- 1.2 and 17.7 +/- 1.7%, respectively. Addition of 10(-5) M inosine had no effect, whereas 10(-4) M inosine enhanced the vasodilation induced by 10(-7) M adenosine to 19.4 +/- 1.7% and that by 10(-6) M adenosine to 23.3 +/- 2.3%. When theophylline (5 X 10(-5) M) was perfused together with 10(-7) M adenosine and 10(-4) M inosine, the vasodilation was almost completely abolished. The present study indicates that inosine alone does not affect pial vessel diameter but potentiates the response of pial arterioles to exogenous adenosine. This potentiating action of inosine may be attributed to an increase in perivascular adenosine and may be explained by the action of inosine as an adenosine uptake inhibitor.

Adenosine↗
PubMed1989

Use of stimulation mapping and corticography in the excision of arteriovenous malformations in sensorimotor and language-related neocortex.

The excision of an arteriovenous malformation (AVM) located within eloquent neocortex presents a formidable neurosurgical challenge. Compromise of the vascular supply to normal surrounding brain or surgical trauma to essential neighboring neocortex may result in unacceptable postoperative neurological morbidity. In addition, successful removal of these lesions without the benefit of intraoperative corticography may leave in situ areas of highly epileptogenic brain, resulting in continued epilepsy. In this report, we describe eight patients who underwent craniotomy and excision of AVMs at our institutions. Six of these lesions were located in the dominant (left) hemisphere, and two were on the right. All patients underwent preoperative testing with Amytal administered via the carotid artery (Wada test). Subsequently, the patient was placed under local anesthesia, and we performed a craniotomy. Electrocorticography was used to identify epileptogenic brain in the region of the AVM and to establish after-discharge thresholds to electrical stimulation. Stimulation-mapping techniques were then used to delineate critical motor, sensory, and language areas. Trial occlusion of feeding vessels was also carried out to document postocclusion neurological deterioration, if any. At a later time, a second procedure was performed under general anesthesia to excise the lesion and any epileptogenic foci, using the cortical maps derived earlier. Using these techniques, it was possible to effect complete excision of these lesions in seven of eight patients without causing additional neurological deficits.

Adolescent↗
PubMed1989

Evaluation of brain death using transcranial Doppler.

Cerebral blood flow velocities in the middle cerebral arteries were measured using transcranial Doppler in 12 patients with conditions that ultimately resulted in brain death. All patients had sustained closed head injury, gunshot wounds to the head, or spontaneous intracerebral hemorrhages. When clinical criteria for brain death were met, a characteristic pattern was found with transcranial Doppler. This pattern consisted of reverberating flow, with forward flow in systole and retrograde flow in diastole. When this pattern was seen, there was arrest of cerebral flow, as measured by radionuclide scanning using technetium, in all patients studied. Transcranial Doppler is a useful technique for easily assessing the arrest of the cerebral circulation.

Adolescent↗
PubMed1989

Intracerebral drug delivery in rats with lesion-induced memory deficits.

Pharmacological treatments directed at increasing cortical acetylcholine activity in patients with Alzheimer's disease have largely been disappointing, perhaps because denervated areas of brain may not be exposed to adequate amounts of drug. A new method has been developed to enable localized intracerebral delivery of neurotransmitter substances using a polymeric drug delivery system. Microspheres of a polyanhydride sebacic acid copolymer were impregnated with bethanechol, an acetylcholinesterase-resistant cholinomimetic. Twenty rats received bilateral fimbria-fornix lesions, producing cholinergic denervation of the hippocampus and marked impairment in spatial memory. The animals were trained for 2 weeks to run after which they received bilateral intrahippocampal implants of saline (five rats), blank polymer (five rats), or bethanechol-impregnated polymer (10 rats). Following implantation, spatial memory was assessed by radial-maze performance testing for 40 days. Untreated lesioned rats showed persistently poor spatial memory, entering maze arms with near random frequency. Similarly, animals treated with saline and blank polymer did not improve after implantation. Rats treated with bethanechol-impregnated microspheres, however displayed significant improvement within 10 days after implantation; this improvement persisted for the duration of the experiment (p less than 0.05, Student's t-test). Histological analysis of regional acetylcholinesterase staining showed widespread loss of activity throughout the hippocampus bilaterally in all animals. The microsphere implants were visible within the hippocampus, with minimal reactive changes in surrounding brain. It is concluded that intracerebral polymeric drug delivery successfully reversed lesion-induced memory deficits, and has potential as a neurosurgical treatment method for Alzheimer's disease and other neurodegenerative disorders.

Anhydrides↗
PubMed1989

CT infusion scanning for the detection of cerebral aneurysms.

Computerized tomography (CT) infusion scanning can confirm the presence or absence of an aneurysm as a cause of spontaneous intracerebral hemorrhage. Eight patients who presented with spontaneous hemorrhage were examined using this technique. In five patients the CT scan showed an aneurysm which was later confirmed by angiography or surgery; angiography confirmed the absence of an aneurysm in the remaining three patients. This method is an easy effective way to detect whether an aneurysm is the cause of spontaneous intracerebral hemorrhage.

Adult↗
PubMed1989

Angioplasty for the treatment of symptomatic vasospasm following subarachnoid hemorrhage.

Angioplasty of narrowed cerebral arteries was performed in 10 patients who became symptomatic from vasospasm following subarachnoid hemorrhage. This procedure was accomplished with a microballoon catheter via percutaneous transfemoral insertion. Patients were selected for treatment if they had delayed neurological deficits due to vasospasm which were not responsive to hypervolemic hypertensive therapy. Eight patients (80%) showed sustained improvement in neurological function following the procedure. In two patients transcranial Doppler ultrasound recordings were obtained which revealed decreased mean blood flow velocities following angioplasty. Two patients died, one from an aneurysmal rebleed, and one secondary to diffuse vasospasm. There was one case of delayed stroke 6 weeks following the procedure. The overall results of this series indicate that in selected cases percutaneous balloon angioplasty can offer marked improvement to patients with ischemic deficits due to vasospasm following subarachnoid hemorrhage.

Adult↗
PubMed1989

Acute subdural hematomas: an age-dependent clinical entity.

Reports prior to 1980 describe overall mortality rates for acute subdural hematomas (SDH's) ranging from 40% to 90% with poor outcomes observed in all age groups. Recently, improved results have been reported with rapid diagnosis and surgical treatment. A relatively large number of older patients (34 patients over 65 years old) were treated recently at Harborview Medical Center, enabling a retrospective comparison with similarly treated younger patients (33 patients aged 18 to 40 years). Clinical information and computerized tomography morphometric data were obtained. Patients in the younger group were most often injured in motor-vehicle accidents (15 cases), whereas falls were most frequent in the older group (19 cases). Patients in both groups were rapidly resuscitated in the field; more than 30% were treated within 1 hour after the time of injury. Injury severity, determined by the admission Glasgow Coma Scale score, was similar for the two groups. Mean acute SDH volume was significantly larger in the older patients than in the younger group (mean +/- standard deviation: 96.2 +/- 117.2 vs. 21.6 + 27.7 cu cm), as was the amount of midline shift (1.2 +/- 1.69 vs. 0.6 +/- 0.75 cm). Surgical treatments were similar, but outcomes were dramatically different for the younger and older patients. Mortality rates were more than four times higher in older patients than in younger ones (74% vs. 18%). Three older patients and 25 younger patients were functional survivors. Old age, a larger SDH volume, and a larger midline shift all correlated with a poor outcome. The results of this study suggest that the pathophysiology of acute SDH varies with age, and that currently employed resuscitation and treatment methods have differentially improved the outcome for younger patients.

Accidental Falls↗
PubMed1988

Stereotactic neutron radiosurgery for arteriovenous malformations of the brain.

A technique employing single fraction neutron radiosurgery for treatment of intracranial vascular malformations has been developed at the University of Washington and is described in this report. The natural history of arteriovenous malformations of the brain is briefly reviewed, along with currently available therapeutic methods for treatment of these lesions. The characteristics of the neutron beam used for radiosurgery are described, along with methods for patient immobilization, radiation treatment planning, dosimetry, and delivery of treatment using this technique.

Fast Neutrons↗
PubMed1988

The effects of dipyridamole and theophylline on rat pial vessels during hypocarbia.

Hypocarbia results in an increase in brain adenosine concentrations, presumably because of brain hypoxia associated with hypocarbic vasoconstriction. It was hypothesized that adenosine limits the degree of hypocarbic vasoconstriction. To test this hypothesis, the effects of dipyridamole and theophylline on CO2 reactivity during hypocarbia were investigated in anesthetized rats. Dipyridamole should reduce the vasoconstriction by potentiating adenosine action, whereas theophylline should increase the vasoconstriction by blocking adenosine receptors. Cortical pial arterioles of mechanically ventilated and anesthetized rats were displayed on a video monitor system through a closed cranial window. Arterial blood pressure and oxygen tension were stable. CO2 reactivity, formulated as 100 X [delta diameter (micron)/resting diameter (micron)]/delta PaCO2 (mmHg), in the hypocarbic phase was calculated before and after topical superfusion of dipyridamole (10(-6) M; n = 7) and theophylline (5 X 10(-5) M; n = 6). CO2 reactivity was significantly decreased after superfusion of dipyridamole (0.57 +/- 0.08; mean +/- SEM) as compared with mock cerebrospinal fluid (CSF) (0.97 +/- 0.17, p less than 0.05, n = 7). On the other hand, CO2 reactivity after superfusion of theophylline was increased (1.63 +/- 0.28) as compared with mock CSF (1.00 +/- 0.20, p less than 0.05, n = 6), indicating that adenosine is involved in hypocarbic vasoconstriction.

Adenosine↗
PubMed1988

Effect of sciatic nerve stimulation on pial arterioles in rats.

The present study documents the microvascular response of the pial circulation in sensory hindlimb cortex to sciatic nerve stimulation. Rats, anesthetized with alpha-chloralose and urethan, were equipped with closed cranial windows, and pial arteriolar diameter was measured during stimulation of the contralateral sciatic nerve. The effects of varying stimulus frequency, intensity, and duration were examined. Optimal stimulus frequency was 5 Hz, but response diminished significantly beyond 10 Hz. Optimal stimulus intensity was 0.2 V. At higher stimulus strength, arteriolar dilation was reduced, but systemic blood pressure rose significantly. At low stimulus frequency and intensities, pial arterioles responded to stimulation with a consistent pattern: initial delay of 1.4 s followed by abrupt dilation to a peak magnitude, subsequent decline to a lesser but still dilated state, and recovery to a resting diameter after the cessation of stimulation. No consistent response profile was discernible at high stimulus intensity and/or frequency. This vasodilatory response was discretely restricted to a limited number of arterioles, confined to the hindlimb somatosensory cortex as confirmed by sensory evoked response. The response of the pial circulation provides a well-characterized model for analysis of brain microcirculation, which presumably is linked to cerebral metabolism.

Animals↗
PubMed1988

Brain xenografts: the effect of cyclosporin A on graft survival.

Animal models of Parkinson's disease and Alzheimer's disease have shown dramatic functional improvement after transplantation of embryonic neurons into denervated regions of the adult brain. Because of the ethical and logistic problems associated with the use of human embryonic brain tissue, cross-species transplants are an attractive alternative. An experimental model of cross-species brain transplantation was developed to evaluate cell survival in untreated and cyclosporin A (CyA)-treated animals. Cholinergic ventral neurons from embryonic mice were transplanted into the frontal lobes of 18 adult Sprague-Dawley rats using a cell suspension technique. Nine animals were treated for 13 days with CyA (10 mg/kg/day) and nine were not treated. Twelve weeks after transplantation, frozen sections through the transplant volume were obtained. Alternate sections were prepared with hematoxylin and eosin and acetylcholine esterase stains. Cell counts through a 2-cu mm volume incorporating the transplant were compared to a contralateral control volume. Eight of the nine untreated transplants were successful (mean transplant cells +/- standard error of the mean: 90.7 +/- 19.4/2 cu mm). All of the nine CyA-treated transplants survived, with mean transplant count 28.7 cells/2 cu mm greater than untreated transplants (mean increase 28.7: p less than or equal to 0.05, Wilcoxon matched-pairs signed ranks test). It is concluded that: 1) this model is useful for quantitating transplant cell survival; 2) untreated xenografts survive well; and 3) a 13-day course of CyA improved long-term graft survival.

Acetylcholinesterase↗
PubMed1987

Role of adenosine in regulation of cerebral blood flow: effects of theophylline during normoxia and hypoxia.

We studied the effects of the methylxanthine theophylline, an adenosine receptor blocker, on cerebral circulation. Cerebral blood flow (CBF) was measured by the retroglenoid outflow and microsphere techniques, and pial circulation changes were observed through a closed cranial window. Intraperitoneal administration of theophylline in normoxic animals resulted in a biphasic response of pial vessels and CBF. At low concentrations (0.05 mumol/g) of theophylline, pial vessel diameter and CBF decreased, whereas vasodilatation and hyperemia were observed at higher levels. After intraperitoneal administration of either 0.05 or 0.2 mumol/g, hypoxic hyperemia was attenuated both during short (c. 30 s) and sustained (c. 2-3 min) hypoxia, as was hypoxic pial arteriolar vasodilatation. These actions of theophylline appear to be due to adenosine receptor blockade, since micromolar concentrations were achieved in cerebrospinal fluid (CSF), and no increases in adenosine 3',5'-cyclic monophosphate concentrations in brain were noted. Moreover, theophylline (either intraperitoneal or topical) blocked pial vasodilatation caused by topically applied adenosine, but had little effect on hypercarbic hyperemia or pial vasodilatation induced by topically applied acetylcholine. The results of these studies suggest that adenosine is involved in the maintenance of resting cerebral vascular tone and has a paramount role in the regulation of CBF during hypoxia.

Adenosine↗