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Biomedical subjects

H R Winn

Publications and source records attributed to H R Winn.

At least 109 records · Page 6Linked to original sources

Moderate hyperglycemia affects ischemic brain ATP levels but not intracellular pH.

We used 31P nuclear magnetic resonance (NMR) spectroscopy to study the effect of moderate hyperglycemia on brain ATP and intracellular pH in a model of severe incomplete forebrain ischemia. Plasma glucose in the hyperglycemic rats was 277 +/- 9 mg/100 ml compared with 115 +/- 10 mg/100 ml in the normoglycemic rats at the onset of ischemia. After 15 min of ischemia, brain ATP levels decreased to 31 +/- 8% in normoglycemic rats vs. 63 +/- 11% in hyperglycemic rats (P < 0.05). Phosphocreatine levels were 31 +/- 9 and 55 +/- 8% for normoglycemic and hyperglycemic rats, respectively. Intracellular pH decreased to the same level (approximately 6.5) in both normoglycemic and hyperglycemic animals after 15 min of ischemia. In summary, we found that moderate hyperglycemia during severe incomplete forebrain ischemia significantly increases ischemic brain ATP levels but does not have a significant effect on intracellular pH. These results support the hypothesis that alterations in brain ATP and adenosine concentrations may be important in the pathogenesis of ischemic tissue injury under moderate hyperglycemic conditions, whereas alterations in tissue pH may be less important.

Adenosine Triphosphate↗

Regulation of blood-brain barrier endothelial cells by nitric oxide.

Nitric oxide (NO) synthesized by vascular endothelial cells is a potent vasodilator substance. The actions of NO extend well beyond its vasodilatory properties, and increasingly, NO has been recognized as an important signal for intercellular and intracellular communication. Recently, NO has been implicated in the regulation of vascular and blood-brain barrier permeability. NO has also been shown to modulate ion channels in excitable cells, thus affecting neuronal firing. We report the results of patch-clamp experiments that show a modulatory action of NO as well as cGMP and cAMP on a hyperpolarization-activated current (Iha) carried by both Na+ and K+ ions in blood-brain barrier endothelial cells. Iha was recorded in cells dialyzed with 0.2 mmol/L GTP-gamma-S to inhibit a large inwardly rectifying potassium current. This ionic current and its modulation by NO may play a role in the regulation of the transport of ions, nutrients, and other molecules to the brain and serve as an integral part of the blood-brain barrier. The modulation of Iha by a cyclic guanosine nucleotide may also explain previous reports suggesting a role for NO in the regulation of blood-brain barrier function.

Animals↗

Comparison of flow and velocity during dynamic autoregulation testing in humans.

BACKGROUND AND PURPOSE: We compared relative changes in middle cerebral artery velocity and internal carotid artery flow during autoregulation testing to test the validity of using transcranial Doppler recordings of middle cerebral artery velocity to evaluate cerebral autoregulation in humans. METHODS: Seven human volunteers had dynamic autoregulation tested during surgical procedures that included exposure of the internal carotid artery. The mean arterial blood pressure and middle cerebral artery velocity spectral outline (Vmax), using transcranial Doppler, and ipsilateral internal carotid artery flow, using an electromagnetic flowmeter, were continuously and simultaneously recorded during transient sharp decreases in blood pressure that were induced by rapid deflation of thigh blood pressure cuffs. The resulting responses of velocity in the middle cerebral artery and flow in the internal carotid artery were compared. RESULTS: Moderate decreases in blood pressure evoked responses in cerebral autoregulation. There were no significant (P = .97) differences between the responses in middle cerebral artery velocity and internal carotid artery flow to the blood pressure decreases. CONCLUSIONS: Relative changes in Vmax accurately reflect relative changes in internal carotid artery flow during dynamic autoregulation testing in humans. Therefore, alterations in middle cerebral artery diameter do not occur to the extent that they introduce a significant error in making these comparisons.

Aged↗

Stereotactic radiosurgery: a review and comparison of methods.

PURPOSE: Stereotactic radiosurgery (SRS) is an evolving modality for treating well-circumscribed intracranial lesions. Different physical methods have been developed to deliver highly localized dose distributions accurately. We review the different methods and the documented clinical results to present a coherent view of radiosurgery, and to aid physicians and physicists in the appropriate use of this modality. DESIGN: A review of the medical physics and clinical literature was conducted. The physical aspects of the different methods and their impact on treatment were summarized. Results were compiled from those individual clinical series with adequate follow-up data to compare the various modalities with respect to treatment outcome for benign tumors, metastases, and vascular malformations. RESULTS: The physical accuracy was comparable between radiosurgical methods. Differences between gamma radiation and linear accelerator methods had little effect on the dose distribution for single isocenter treatments. Charged particle methods could produce better dose localization for large lesions (> 25 cm3) than was possible with photon methods. Clinical results indicate similar lesion control rates between all radiosurgical methods. There was a progressive increase in the median size of treated lesions for gamma radiation, linear accelerator, and charged particle methods. CONCLUSION: For small lesions (< 5 cm3), physical dose distributions are similar for the photon methods, but linear accelerator methods offer more flexibility for the treatment of intermediate-sized (5 to 25 cm3) lesions in applying future technical developments. More clinical results are needed before firm conclusions can be drawn on the type of lesions to be treated, and the dose-volume parameters to be used.

Brain Neoplasms↗

Succinylcholine does not change intracranial pressure, cerebral blood flow velocity, or the electroencephalogram in patients with neurologic injury.

The effect of succinylcholine (SCh) on intracranial pressure (ICP) was studied in 10 mechanically ventilated patients (Glasgow coma scale score 3-10, median 6) being treated for increased ICP in an intensive care unit. Mean arterial blood pressure (MAP), ICP, processed electroencephalogram (EEG), and mean middle cerebral artery blood flow velocity (V mca) were monitored. Baseline measurements after saline injection were obtained for 5 min. SCh (1 mg/kg) was administered intravenously and the above variables were monitored for 15 min. Neither saline nor SCh cause any significant change in cerebral perfusion pressure, MAP, V mca, EEG, or ICP. We conclude that in brain-injured patients, SCh did not alter cerebral blood flow velocity, cortical electrical activity, or ICP.

Adult↗

A critique of the intraoperative use of jugular venous bulb catheters during neurosurgical procedures.

We examined the intraoperative use of jugular venous bulb catheters in 100 consecutive patients undergoing neurosurgical procedures. The catheters were successfully placed after induction of anesthesia in 99 patients using an aseptic technique. The efforts were abandoned after four attempts in the remaining patient. The mean time of insertion was 94 s (SD 108, range 15-420). Carotid artery puncture on two occasions controlled by firm pressure was the only complication. Arterial blood pressure, PaCO2, PaO2, and jugular venous bulb oxygen saturations (SjVO2) were intermittently measured at set intervals throughout the operation. We defined cerebral venous desaturation as 1) none (SjVO2 > 50%), 2) mild (45% < SjVO2 < 50%), and 3) severe (SjVO2 < 45%). We graded the usefulness of the catheter as 1) not useful (NU), SjVO2 > 50% and PaCO2 > 25 mm Hg; 2) useful (U1), SjVO2 > 50% and PaCO2 < 25 mm Hg; intervention, no increase in PaCO2; 3) useful (U2), SjVO2 < 50% and PaCO2 < 25 mm Hg; intervention, increase PaCO2 to improve SjVO2; 4) useful (U3), SjVO2 < 50% and PaCO2 > 25 mm Hg; intervention, nonventilatory action to increase SjVO2 (e.g., infusion of mannitol). Mild desaturation was detected in 24 patients and severe desaturation was present in 17 patients. We found SjVO2 monitoring to be useful in 60 of 99 patients studied. It was useful for detecting and treating cerebral venous desaturation in 13 of 18 patients with intracranial hematomas (subdural, epidural, and intracerebral hematomas), 9 of 18 patients with intracerebral tumors, 27 of 45 patients with cerebral aneurysms, and 6 of 8 patients with other intracranial pathology.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Mild pediatric traumatic brain injury: adjusting significance levels for multiple comparisons.

The outcome following mild traumatic brain injury (TBI) is controversial. We addressed this topic in a study of neurobehavioural and 'real-world' functioning among 53 children with mild TBI and their matched controls, using statistical methods recently developed for multiple comparisons. Because the study involved calculation of 414 p-values, four methods of adjustment for multiple comparisons, including the Bonferroni method, were used to avoid 'false-positive' statistical significance. The additional three methods allowed greater insight into the data than provided by the standard Bonferroni adjustment. Results showed that at initial testing, three areas of 'real-world' functioning (eating, domestic and home/community living skills) had weak but statistically significant associations with mild injury. No other specific areas of neuro-behavioural or 'real-world' functioning had plausible associations with the injury either initially, at 1 year, or when changes over the year were considered. However, the adjustment for multiple comparisons provided additional results. There were statistical significant associations of the injury with the entire domain of neurobehavioural variables both initially and at 1 year. These results suggest that the injury affects a spectrum of neurobehavioural skills weakly, rather than a single area substantially. The gain from using multiple comparison methods is discussed.

Activities of Daily Living↗

Severe symptomatic vasospasm: the role of immediate postoperative angioplasty.

The clinical success of angioplasty for symptomatic vasospasm following subarachnoid hemorrhage (SAH) depends on early intervention and can best be achieved after the aneurysm is occluded. However, patients presenting with unsecured ruptured aneurysms and established clinical vasospasm offer a dilemma for the surgeon. The authors describe the cases of five such patients who underwent acute clipping of aneurysms followed by immediate postoperative angioplasty between 1988 and 1992. All were referred at least 5 days after SAH. Severe vasospasm compatible with the clinical presentation was confirmed by angiography. The patients met the department's criteria for angioplasty but, because of unclipped aneurysms, were first taken patients met the department's criteria for angioplasty but, because of unclipped aneurysms, were first taken to the operating room for a craniotomy and aneurysm obliteration. Angiography was repeated immediately after surgery. Arterial narrowing had progressed during surgery in two patients. In all patients, postoperative mechanical dilatation was achieved with the use of a silicone microballoon. Following angioplasty, transcranial Doppler ultrasound flow velocities and single-photon emission computerized tomography evaluation indicated improved cerebral perfusion compared to preoperative determinations. Four patients improved clinically and made a good recovery. In this subgroup of patients presenting with proven symptomatic vasospasm and an unclipped but ruptured aneurysm, urgent surgical obliteration of the aneurysm followed by immediate postoperative angioplasty may be a safe and reasonable means to improve outcome.

Adult↗

Tentorial meningiomas.

Tentorial meningiomas are encountered relatively infrequently, but it is nonetheless important to be aware of their variable clinical presentations and the need for individualized preoperative assessment and surgical management. The challenges presented by these lesions are due in large part to the complexity and variety of neurovascular structures associated with the tentorium. As is true for all meningiomas, the goal of operation is complete resection with limited morbidity and mortality. Preoperative assessment with CT or MR imaging or both and angiography with embolization, when possible, is advocated for all patients. The choice of surgical approach is dictated by the location of the lesion, dural origin, and involvement of major neurovascular structures. With extended surgical approaches, combining infratentorial and supratentorial exposure, one can attempt complete tumor resection even in patients with extensive skull base involvement. However, if complete resection presents an unacceptable risk of neurologic morbidity, one must consider adjuvant therapy. Radiotherapy (conventional external beam or stereotactic) has been shown to be of some benefit in stabilizing residual disease or delaying recurrence; adjuvant chemotherapy with antiprogesterone agents is still undergoing clinical evaluation.

Adolescent↗

White matter ischemia on brain SPECT.

Four patients were shown to have ischemic injury to the posterior limb of the internal capsule on brain SPECT with 99mTc-HMPAO. These findings were later corroborated by transmission CT scans in three patients. In the interpretation of high-resolution SPECT imaging of regional cerebral blood flow, it is important to inspect the deep white and gray matter activity for asymmetry and perfusion deficits. The blood flow to the diencephalon, which is critical for brain function, can be imaged with high-resolution brain SPECT. The early ascertainment of ischemic changes in the diencephalon may lead to important patient management decisions.

Adult↗

Endovascular treatment of vasospasm.

Angioplasty has become an important tool in the treatment of symptomatic vasospasm. The recent advent of intra-arterial papaverine infusion for the treatment of vasospasm serves to complement angioplasty. The use of these techniques in the treatment of symptomatic vasospasm is discussed.

Angioplasty, Balloon↗

Magnetic resonance neurography.

Radiological methods exist for generating tissue-specific images of bone, vessels, lymphatics, abdominal viscera, and the central nervous system, but there has been no reliable means to generate a clinical image of a nerve. We present the first "image neurogram" and report a method for producing such images by use of commercial magnetic resonance imaging systems. The image depicts a human nerve in situ in relation with a nerve graft, wherein the nerve is rendered in isolation much like a vessel appears in isolation in a subtraction angiogram.

Adult↗

Severity of pediatric traumatic brain injury and neurobehavioral recovery at one year--a cohort study.

As part of an ongoing longitudinal cohort study of children with mild, moderate, and severe traumatic brain injury and their matched controls, the neurobehavioral status of 94 case-control pairs was assessed one year after initial postinjury testing. There was a statistically significant dose-response association of severity with performance in all six domains of neurobehavioral functioning (intelligence, adaptive problem solving, memory, academic performance, motor performance, and psychomotor problem solving) with Spearman correlation coefficients of up to -.35, p < .001. The strongest correlations between severity and outcome were in the domains of intelligence, academic performance, and motor performance. Recovery over the year was also dependent on the severity of brain injury. Because mildly injured cases had negligible initial deficits, recovery was not at issue. However, for moderately and severely injured children, the degree of initial impairment was related to the magnitude of both recovery and residual deficit. Results showed that the use of population normative values to evaluate impairment was misleading. Although the mean scores of all severity groups fell within the normal range of standardized tests, the means for the moderately and severely injured were substantially below those of their matched controls on many tests.

Adolescent↗

Stroke following rottweiler attack.

A previously healthy 50-year-old man suffered a major right cerebral infarction shortly after receiving head and neck bites in an attack by two rottweilers. Arteriography revealed occlusion of the right middle cerebral artery, an intimal flap and pseudoaneurysm in the high right internal carotid artery just proximal to the skull base, and an obstructed right vertebral artery. The powerful jaw mechanism of rottweilers and other large mastiff-type dogs makes their bites particularly destructive. The predilection of these animals for attacking the head and upper body makes occult crush injury to the extracranial cerebral vessels an important diagnostic consideration following such attacks.

Animals↗

Changes in pial arteriolar diameter and CSF adenosine concentrations during hypoxia.

We measured the changes in pial arteriolar diameter and CSF concentrations of adenosine, inosine, and hypoxanthine during hypoxia in the absence and presence of topically applied dipyridamole (10(-6) M) and erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA; 10(-5) M). Closed cranial windows were implanted in halothane-anesthetized adult male Sprague-Dawley rats for the observation of the pial circulation and collection of CSF. The mean resting arteriolar diameter in mock CSF was 31.2 +/- 5.9 microns. Topically applied dipyridamole and EHNA, in combination, caused a slight but significant (p < 0.05) increase in resting arteriolar diameter (33.8 +/- 4.3 microns). With mock CSF, moderate hypoxia caused a 22.1 +/- 9.7% increase in pial vessel diameter. Topically applied dipyridamole and EHNA significantly (p < 0.01) potentiated pial arteriolar vasodilation in response to hypoxia. Moreover, the potentiating effects of dipyridamole and EHNA during hypoxia were completely abolished by theophylline (0.20 mumol/g, i.p.; p < 0.05), an adenosine receptor antagonist. Resting concentrations of adenosine, inosine, and hypoxanthine in the subwindow CSF were 0.18 +/- 0.09, 0.35 +/- 0.21, and 0.62 +/- 0.12 microM, respectively. In the absence of dipyridamole and EHNA, these levels were not affected by sustained moderate hypoxia (PaO2 = 36 +/- 6 mm Hg). However, in the presence of dipyridamole and EHNA, the concentration of adenosine in the CSF during hypoxia was significantly (p < 0.05) increased. Our data indicate that dipyridamole and EHNA potentiate hypoxic vasodilation of pial arterioles while simultaneously increasing extracellular adenosine levels, thus supporting the hypothesis that adenosine is involved in the regulation of cerebral blood flow.

Adenine↗

The effect of alfentanil on cerebral blood flow velocity and intracranial pressure during isoflurane-nitrous oxide anesthesia in humans.

BACKGROUND: Intravenous opioids often are used as a component of anesthesia during neurosurgical procedures. However, the cerebrovascular effects of alfentanil administered to patients are controversial. In this study, the effect of alfentanil in patients with and without intracranial pathology was studied. METHODS: Sixteen neurosurgical patients and 16 patients scheduled for orthopedic procedures were studied. Anesthesia was maintained with isoflurane (0.4-0.6 vol% inspired) and nitrous oxide (50%) in oxygen. Within each group, the patients were assigned randomly to receive either 25 or 50 micrograms/kg intravenous alfentanil. During normocapnia and without surgical stimulation, the right middle cerebral artery flow velocity, and mean arterial pressure were measured every minute for 10 min after the administration of alfentanil. In the neurosurgical patients, intracranial pressure, cerebral perfusion pressure, and cerebral arteriovenous oxygen content difference were determined also. Neurosurgical patients received intravenous phenylephrine to maintain mean arterial pressure as needed. RESULTS: There was no significant change in middle cerebral artery flow velocity and arteriovenous oxygen content difference in the neurosurgical patients. In the high-dose group, intracranial pressure increased by 2 mmHg at 4 min but was otherwise unchanged. Despite phenylephrine administration, there was an immediate but transient decrease in mean arterial pressure in the high-dose group and a corresponding decrease in cerebral perfusion pressure. In the orthopedic patients, mean arterial pressure decreased significantly. Middle cerebral artery flow velocity decreased in the high-dose group but remained unchanged in the low-dose group. CONCLUSIONS: Based on the flow velocity and metabolic data, alfentanil is neither a cerebral vasodilator nor a vasoconstrictor in these doses. Furthermore, there was no clinically significant increase in intracranial pressure when alfentanil was administered in either dose.

Adult↗