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Biomedical subjects

H R Winn

Publications and source records attributed to H R Winn.

At least 127 records · Page 7Linked to original sources
PubMed1993

ATP-sensitive K+ channels in rat aorta and brain microvascular endothelial cells.

The endothelium plays an important role in the modulation of vascular tone and blood cell activation. Extensive work has demonstrated that the release of endothelium-derived relaxing factor (EDRF) from the endothelium is evoked by a number of physical and chemical stimuli requiring Ca2+. Because endothelial cells do not express voltage-dependent Ca2+ channels, Ca2+ influxes following receptor activation may be facilitated by cell hyperpolarizations mediated by the activation of K+ conductances. There has been recent interest in the role of ATP-sensitive K+ channels (KATP) suggesting that KATP may play a role in the regulation of blood flow. We have investigated the electrophysiological properties of an ATP-sensitive K+ conductance in whole cell and membrane patches from rat aorta and brain microvascular endothelial cells. Whole cell as well as single-channel currents were increased by either intracellular dialysis of ATP or application of glucose-free/NaCN (2 mM) solutions. Both currents were reversibly blocked by glibenclamide (1-100 microM). The KATP channel opener pinacidil (30 microM) caused activation of an outward current in the presence of physiological intracellular ATP concentrations. In inside-out patches, 10 microM-1 mM ATP invariably caused a dramatic decrease in channel activity. We conclude that both rat aorta and brain microvascular endothelial cells express KATP channels. KATP may play a role in the regulation of endothelial cell resting potential during impaired energy supply and therefore modulate EDRF release and thus cerebral blood flow.

Adenosine Triphosphate↗
PubMed1993

Effects of adenosine and its analogues on isolated intracerebral arterioles. Extraluminal and intraluminal application.

We evaluated the responses of brain parenchymal arterioles to intraluminal and extraluminal application of adenosine and its analogues. Intracerebral arterioles (28.4- to 60.3-microns diameter) were isolated from Sprague-Dawley rats, cannulated with micropipettes, and perfused in vitro. Both extraluminal and intraluminal adenosine, 5'-(N-ethylcarboxamido)adenosine (NECA), R-N6-(phenylisopropyl)adenosine (R-PIA), and S-N6-(phenylisopropyl)adenosine (S-PIA) elicited concentration-dependent dilation of these arterioles, but intraluminal application was less potent and efficacious than extraluminal application. Inosine was not vasoactive. A common order of agonist potency (NECA > adenosine > R-PIA > or = S-PIA) was determined for both extraluminal and intraluminal application. Theophylline (10 microM) caused a rightward shift of the adenosine concentration-response curve and a 50-fold reduction in potency. Intraluminal theophylline was one sixth as effective as extraluminal theophylline in antagonizing the extraluminal adenosine response, whereas intraluminal 8-sulfophenyltheophylline, a polar theophylline derivative, was ineffective. Polyadenylic acid (PolyA, 1 microM), an adenosine polymer that does not penetrate the endothelium, induced a dilation of 44.2 +/- 5.3% when applied extraluminally but had no effect when infused intraluminally. The dilator effect of PolyA was antagonized by theophylline. We conclude that: (1) intraluminal adenosine and its analogues are effective dilators of intracerebral arterioles, (2) the dilator effects of both intraluminally and extraluminally applied adenosine are predominantly mediated by A2-type receptors, and (3) adenosine receptors mediating vasodilation are not present on the luminal surface of the endothelium.

Adenosine↗
PubMed1993

Emergent aneurysm clipping without angiography in the moribund patient with intracerebral hemorrhage: the use of infusion computed tomography scans.

The authors report their experience with 25 patients (mean age, 44.3 +/- 12.1 years) with an intracerebral hematoma (ICH) from a ruptured aneurysm who were emergently operated on without angiography. Instead, preoperative high-resolution infusion computed tomography (CT) scans were used to identify the aneurysm causing the hemorrhage. In all patients, the preoperative Glasgow Coma Scale score was < 5 and brain stem compression was evident. ICH was present in the frontal or temporal lobe and was often associated with intraventricular hemorrhage (n = 17) and significant (> 1 cm) midline shift (n = 18). Infusion CT scans correctly identified the aneurysm in all patients (middle cerebral artery, 18; posterior communicating artery, 2; carotid bifurcation, 3; anterior communicating artery, 2). Partial evacuation of the hematoma guided by infusion CT scan was usually required first to clip the aneurysm definitively using standard microvascular techniques. Intraoperative rupture occurred twice, and temporary clips were used on four occasions. Lobectomy (n = 8), decompressive craniotomy (n = 15), and ventriculostomy (n = 8) were required to control cerebral swelling. All patients underwent postoperative angiography to confirm aneurysm obliteration. Eleven unruptured aneurysms were subsequently identified. Nine had been predicted by infusion scan. Twelve patients survived, eight of whom were only moderately disabled and were independent at 6-months' follow-up. Of the 13 patients who died, all except one died within 4 days of admission. The authors conclude that although angiographic verification before aneurysm surgery is preferable, in the moribund patient with intracerebral hemorrhage, infusion CT scanning provides sufficient information concerning vascular anatomy to allow rational emergency craniotomy and aneurysm clipping.

Adult↗
PubMed1993

Mild pediatric traumatic brain injury: a cohort study.

Using a prospective, cohort design, we investigated whether children with mild traumatic brain injury (TBI) differed from individually matched controls on measures of intellectual, neuropsychological, academic, and "real world" functioning. Subjects included children between the ages of 6 and 15 years who sustained mild, moderate, and severe closed head injuries and were consecutively identified on presentation to the emergency departments of two regional, university medical centers. One hundred twenty-nine children were eligible for enrollment. Seventeen refused enrollment. Fifty-nine of the 112 enrolled children were classified as mildly injured. Six of these children dropped out, leaving 53 mildly injured cases for analysis. Individually matched controls from the classroom of the injured cases were identified based on age, gender, and premorbid academic achievement and behavior. Assessment measures included standardized intellectual, neuropsychological, and academic measures. Also, parent and teacher questionnaires, measuring social, educational, domestic, and community living skills were used. Among 51 outcome variables only five were significantly associated with injury at initial or 1-year testing after adjusting for multiple comparisons. However, these five associations were either very weak or implausible. Results from this study suggest that mild TBI produces virtually no clinically significant long-term deficits in intellectual, neuropsychological, academic, or "real world" functioning.

Activities of Daily Living↗
PubMed1993

Surgical resection of epileptogenic cortex associated with structural lesions.

In this article we have reviewed the available data for postsurgical seizure control in patients with both structural lesions and seizures. There is evidence that simple excision alone will control seizures in some patients, whereas others require, in addition, seizure surgery with resection of epileptogenic cortex. When available studies are reviewed and submitted to meta-analysis, however, we have found that more patients are seizure free at 2-year follow-up after seizure surgery than after simple excision. Seizure control is one of the many factors that influence the choice of surgical approach. Therefore, we do not recommend that all patients with structural lesions and seizures disorders undergo seizure surgery. Rather, for those patients with a structural lesion in whom seizures are medically intractable, our review supports excision of the structural lesion as well as resection of the epileptogenic cortex to provide the patient with the best opportunity of seizure control.

Cerebral Cortex↗
PubMed1992

Effect of nitrous oxide on intracranial pressure after cranial-dural closure in patients undergoing craniotomy.

After cranial-dural closure, nitrous oxide (N2O) may diffuse into and expand an entrapped volume of intracranial air, thereby increasing intracranial pressure (ICP). We performed a prospective clinical study to determine the effect of continuation of N2O after dural closure on ICP in patients undergoing craniotomies. Patients were randomly assigned in a 1.5:1 ratio into a group in which N2O was continued after dural closure (N2O, n = 15) or a group in which N2O was discontinued and replaced with nitrogen (N2, n = 9) at the time of dural closure. PaCO2 was normal prior to closure, and end-tidal PCO2 was kept constant after dural closure. Ipsilateral ICP was recorded at 5-min intervals after dural closure until completion of skin closure and immediately postoperatively. Presence of intracranial air was determined by head computed tomography scan within the first postoperative hour. ICP at the time of dural closure did not differ between the groups (N2O: 3 +/- 2 mmHg vs. N2:5 +/- 1 mmHg). Intraoperatively, ICP did not change after dural closure, regardless of whether N2O was continued or discontinued. Postoperatively, ICP was reduced, with a significant decrease in ICP (P less than 0.01) observed only in the N2O group. Postoperative computed tomography scans demonstrated the presence of intracranial air in all patients, with most exhibiting a mild to moderate degree of pneumocephalus. We conclude that continuation of N2O after dural closure did not affect ICP during the craniotomy closure. These results suggest that it is not necessary to discontinue N2O prior to dural closure for reasons of avoiding expansion of intracranial air and increasing ICP.

Adult↗
PubMed1992

Intraventricular hemorrhage in blunt head trauma: an analysis of 43 cases.

Before the advent of computed tomography, intraventricular hemorrhage (IVH) from any source was thought rare and invariably fatal. Although intraventricular blood is readily identifiable with computed tomography, there has been little systematic study of its significance in blunt head trauma. Forty-three patients with traumatic IVH were prospectively identified in 1 year at Harborview Medical Center (University of Washington). Most were victims of motor vehicle accidents and suffered severe head injuries. IVH occurred alone in two patients; superficial contusions and subarachnoid hemorrhage were the most common associated finding. Blood was present in only one or both lateral ventricles in 25 patients; only the 3rd or 4th ventricles in 4 and all ventricles in 14 instances. There were 3 intracerebral hematomas and 14 basal ganglion hemorrhages. All of the former and half of the latter communicated with the adjacent lateral ventricle. Extra-axial hematomas appeared more common when only the lateral ventricles were involved, whereas corpus callosum or brain-stem hemorrhage appeared more likely when all the ventricles were involved. Acute hydrocephalus was rare, and ventricular drainage was needed in only four cases. Intracranial pressure (ICP) was elevated (> 15 mm Hg) in 46% of patients. The amount of IVH was related inversely with the Glasgow Coma Scale, but not with increased ICP. The presence of IVH indicated a poor outcome, with only half of the patients being independent at a 6-month follow-up. Poor outcome was associated with increasing age, low admission Glasgow Coma Scale, the presence of space occupying lesions if only the lateral ventricles were involved, and hemorrhage in all four ventricles.(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living↗
PubMed1992

Resolution of petrous internal carotid artery stenosis after transluminal angioplasty. Case report.

Percutaneous transluminal angioplasty is commonly used for treatment of peripheral vascular disease, but only recently has it been applied to craniocervical lesions. The successful use of percutaneous transluminal angioplasty for treatment of an isolated high-grade stenosis of the petrous internal carotid artery is described in a patient with progressive ischemic symptoms despite maximum medical management. At his 2-year follow-up examination, the patient remained asymptomatic with angiographic evidence of progressive resolution of the stenotic lesion and indirect evidence of improved hemispheric blood flow ipsilateral to the lesion. Percutaneous transluminal angioplasty may provide an effective means of treatment for selective intracranial artherosclerotic stenosis.

Aged↗
PubMed1992

Acute cauda equina syndrome from a ruptured aneurysm in the sacral canal. Case report.

The case is presented of a young woman with acute cauda equina syndrome from a ruptured aneurysm in the sacral canal. The lesion was associated with pathological enlargement of the lateral sacral arteries bilaterally, which presumably occurred to provide cross-pelvic collateral flow in response to the diversion of the right internal iliac artery for renal transplantation. The patient presented with signs and symptoms of spontaneous spinal epidural hemorrhage. The radiographic features of this lesion are described. In addition to angiography and partial embolization of the vascular supply, contrast-enhanced high-resolution computerized tomography was essential in the diagnosis and treatment of this unique aneurysm.

Acute Disease↗
PubMed1992

Brain SPECT and the effect of cerebral angioplasty in delayed ischemia due to vasospasm.

Cerebral vasospasm is a major determinant of outcome after subarachnoid hemorrhage (SAH). Brain SPECT with 99mTc-HMPAO was obtained before and after cerebral angioplasty in 10 patients with delayed ischemia due to vasospasm. Eight patients had clinically evident neurologic improvement after the procedure. Visual interpretation and an internal-reference (cerebellum), manual, semi-quantitative region of interest (ROI) analysis revealed improvement of regional cerebral blood flow (rCBF) in 9 out of 10. There were disagreements between the visual and ROI analysis in the two that did not improve clinically. For all 10, the average increase per anterior circulation vessel dilated (n = 17) was 8.8% by comparison of the corticocerebellar ratios. For the eight that improved, the average increase was 10.5%. Brain SPECT is valuable for evaluating delayed cerebral ischemia caused by vasospasm after SAH and is useful to document the changes in rCBF induced by angioplasty. It is possible that SPECT may be useful to detect critical reductions in perfusion before clinical deficits develop, thereby offering the potential to identify candidates for early treatment with angioplasty.

Adult↗
PubMed1992

Severity of pediatric traumatic brain injury and early neurobehavioral outcome: a cohort study.

Traumatic brain injury (TBI) is a major cause of pediatric disability. Its neurobehavioral sequelae can often be difficult to distinguish from premorbid problems. To establish the early neurobehavioral consequences of TBI, we compared a cohort of brain injured children with controls, individually matched on premorbid characteristics. Ninety-eight children, aged 6 to 15 years, with mild, moderate, and severe closed head injuries, were consecutively identified on presentation to two regional medical centers. Individually selected controls were matched for age, gender, school grade, behavior, and academic performance. Intellectual, neuropsychologic, and academic assessments were undertaken 3 weeks after full orientation was achieved. No significant case-control differences were found on 20 variables measuring premorbid status. The pattern of decline in performance with increasing severity of brain injury was consistent for measures assessing intelligence, memory, speeded motor performance, adaptive problem solving, and academic performance. Moderately and severely injured patients performed at normal levels in reference to standardized intellectual norms, but they showed impairment when compared with their matched controls. The impairments uncovered in this study place moderately and severely brain injured children at risk for problems in the acquisition of academic skills and higher-order cognitive abilities.

Achievement↗
PubMed1991

Carotid endarterectomy and prevention of cerebral ischemia in symptomatic carotid stenosis. Veterans Affairs Cooperative Studies Program 309 Trialist Group.

OBJECTIVE: To determine whether carotid endarterectomy provides protection against subsequent cerebral ischemia in men with ischemic symptoms in the distribution of significant (greater than 50%) ipsilateral internal carotid artery stenosis. DESIGN: Prospective, randomized, multicenter trial. SETTING: Sixteen university-affiliated Veterans Affairs medical centers. PATIENTS: Men who presented within 120 days of onset of symptoms that were consistent with transient ischemic attacks, transient monocular blindness, or recent small completed strokes between July 1988 and February 1991. Among 5000 patients screened, 189 individuals were randomized with angiographic internal carotid artery stenosis greater than 50% ipsilateral to the presenting symptoms. Forty-eight eligible patients who refused entry were followed up outside of the trial. OUTCOME MEASURES: Cerebral infarction or crescendo transient ischemic attacks in the vascular distribution of the original symptoms or death within 30 days of randomization. INTERVENTION: Carotid endarterectomy plus the best medical care (n = 91) vs the best medical care alone (n = 98). RESULTS: At a mean follow-up of 11.9 months, there was a significant reduction in stroke or crescendo transient ischemic attacks in patients who received carotid endarterectomy (7.7%) compared with nonsurgical patients (19.4%), or an absolute risk reduction of 11.7% (P = .011). The benefit of surgery was more profound in patients with internal carotid artery stenosis greater than 70% (absolute risk reduction, 17.7%; P = .004). The benefit of surgery was apparent within 2 months after randomization, and only one stroke was noted in the surgical group beyond the 30-day perioperative period. CONCLUSIONS: For a selected cohort of men with symptoms of cerebral or retinal ischemia in the distribution of a high-grade internal carotid artery stenosis, carotid endarterectomy can effectively reduce the risk of subsequent ipsilateral cerebral ischemia. The risk of cerebral ischemia in this subgroup of patients is considerably higher than previously estimated.

Aged↗
PubMed1991

Neurobehavioral effects of phenytoin prophylaxis of posttraumatic seizures.

In order to determine potential negative neurobehavioral effects of phenytoin given to prevent the development of posttraumatic seizures, 244 subjects were randomized to phenytoin or placebo. They received neurobehavioral assessments at 1 and 12 months postinjury while receiving their assigned drug and at 24 months while receiving no drugs. In the severely injured, phenytoin significantly impaired performance at 1 month. No significant differences were found as a function of phenytoin in the moderately injured patients at 1 month or in either severity group at 1 year. Patients who stopped receiving phenytoin according to protocol between 1 and 2 years improved more than corresponding placebo cases on several measures. We conclude that phenytoin has negative cognitive effects. This, combined with lack of evidence for its effectiveness in preventing posttraumatic seizures beyond the first week, raises questions regarding its use for long-term prophylaxis. Our findings do not negate phenytoin's proven efficacy in controlling established seizures nor do they indicate that its cognitive effects are worse than other anticonvulsant drugs.

Adult↗