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Biomedical subjects

R G Dacey

Publications and source records attributed to R G Dacey.

At least 55 records · Page 3Linked to original sources

New management techniques in neurosurgery.

New management techniques continue to be explored by neurosurgeons in order to improve their subspecialty, as well as medicine in general. This year has seen advances in many aspects of cerebrovascular surgery, traumatic brain and spinal cord injury, and chemotherapy for neoplastic disease. Stereotaxis also continues to be a strong alternative for the guidance and treatment of various pathological entities. The basis for developing new management techniques in neurosurgery continues to be rooted in the results of stringent basic science research and well-designed clinical trials.

Brain Injuries↗

Differential effects of pentobarbital on intracerebral arterioles and venules of rats in vitro.

The vasoactive properties of pentobarbital (PB) were studied in intracerebral arterioles and venules (diameter, 30-90 microns). These vessels mediate changes in cerebrovascular resistance and capacitance, respectively. Mean control vessel diameters of arterioles and venules at pH 7.3 were 53.9 +/- 2.8 microns and 78.4 +/- 4.3 microns, respectively. Both arterioles and venules dilated when the pH of the extraluminal solution was lowered to 6.8 and constricted when the pH was raised to 7.6. PB, 10(-6) to 10(-2) mol/L, dilated intracerebral arterioles in a dose-dependent manner at pH 7.3, reaching a maximal dilation of 129.7 +/- 3.1% of control diameter at a dose of 10(-3) mol/L. In contrast, PB at 10(-6) to 10(-2) mol/L failed to produce significant changes in the diameter of intracerebral venules. In addition, PB at 10(-3) mol/L significantly inhibited arteriolar constriction induced by KCl (120 mmol/L), but not venular constriction. The present study suggests that intracerebral venules are relatively less responsive to PB than cerebral arterioles and peripheral veins. In addition to its effect on cerebral metabolism. PB may act to redistribute venous blood volume from cerebral veins to more responsive peripheral veins, thereby decreasing intracranial blood volume and intracranial pressure.

Animals↗

Posterior fossa epithelial cyst of ectodermal origin.

The case of a large ventral cyst of the posterior fossa of probable ectodermal origin in a 33-year-old patient is presented. Intracranial epithelial cysts are rare, and their histogenesis is a subject of controversy. Previous reports have hypothesized either a neuroepithelial or endodermal origin for the majority of these cysts. This case is unusual because it is the first case, to our knowledge, where melanocytes and melanin have been demonstrated within the cyst wall. These findings suggest an ectodermal origin for this cyst.

Adult↗

Differential effects of intra- and extraluminal endothelin on cerebral arterioles.

The differential effects of intraluminal and extraluminal application of endothelin, the endothelium-derived constricting factor, were studied in isolated intracerebral arterioles that were cannulated and perfused in vitro. Extraluminal and intraluminal application of 10(-8) M endothelin constricted the arterioles to 38.2 +/- 6.7 and 75.1 +/- 5.7% of the control diameter, respectively. Constrictions induced by either the intraluminal or the extraluminal application of endothelin were inhibited in a Ca(2+)-free solution. Nimodipine attenuated, but did not completely abolish, the constriction induced by the extraluminal application of endothelin, but it did abolish the constriction induced by the intraluminal application. The duration of vasoconstriction also differed between intra- and extraluminal application. Vessel diameter quickly returned to the control value as soon as intraluminal perfusion of endothelin was terminated. In contrast, the constriction induced by extraluminal application of endothelin lasted much longer and was difficult to reverse. The differential effect of intraluminal and extraluminal endothelin application appears to reflect the important barrier-function of the cerebrovascular endothelium of intracerebral arterioles.

Animals↗

Effects of hypothermia and hyperthermia on the reactivity of rat intracerebral arterioles in vitro.

The effects of hypothermia and hyperthermia on the cerebral microcirculation were studied using isolated perfused intracerebral (parenchymal) arterioles obtained from rats. In a temperature-dependent manner, hypothermia (20.0 degrees to 35.0 degrees C) dilated the spontaneous tone developed by the arterioles and also diminished their contractile response to potassium and prostaglandin F2 alpha. In contrast, hyperthermia (40.0 degrees to 45.0 degrees C) induced a biphasic response consisting of initial vasoconstriction and secondary vasodilation. Exposure of the vessels to 45.0 degrees C for 30 minutes irreversibly abolished the spontaneous tone and responsiveness of the arterioles when the temperature of the preparation was returned to 37.5 degrees C. In calcium-free solutions, however, the arteriolar diameter was not affected within a temperature range of 20.0 degrees to 45 degrees C. Furthermore, arterioles that had been in a calcium-free solution during exposure to 45 degrees C temperature recovered their viability at 37.5 degrees C. These results suggest that changes in ambient temperature alter calcium-induced contraction in arteriolar smooth muscle, and that the irreversible effects of hyperthermia on the arterioles are dependent upon extracellular calcium. These studies indicate that alterations in brain temperature may affect the pathogenesis of cerebral ischemia by mechanisms that are in part independent of parenchymal metabolism.

Analysis of Variance↗

The management of mild and moderate head injuries.

The majority of patients seeking medical care after head trauma have sustained injuries of mild or moderate severity, i.e., GCS scores of 13 to 15 or 9 to 12, respectively. Mortality rates under these circumstances are generally low; however, serious complications must be detected and treated early. The initial evaluation involves determination of level of consciousness and examination for the presence of focal neurologic deficits. Skull radiography has a limited role in the management of mild and moderate head injuries, but consideration must be given to local factors such as the availability of cranial CT. CT scanning is a safe, noninvasive, and generally cost-effective means of assessing patients at risk for developing intracranial complications. The role of MR imaging in evaluating minor head injuries is not yet established. Patients with an altered level of consciousness require hospitalization in essentially all cases. Selected patients with a GCS score of 15 also benefit from overnight hospitalization and observation. After mild and moderate head injury, significant neuropsychologic deficits are frequent, but are generally finite in their duration. Postconcussive symptoms are also generally self-limited. Although objective evidence suggests that structural brain damage results from mild injuries, the relationship between postconcussional symptoms and structural damage is unclear. Persistent postconcussional symptomatology probably arises from a combination of physiogenic and psychogenic causes. It is possible that early patient education and reassurance will reduce the incidence of prolonged postconcussional symptomatology.

Brain Concussion↗

Effects of HA1077, a novel calciumantagonistic spasmolytic agent on intracerebral arterioles of rats.

The effects of the new spasmolytic agent HA1077, which belongs to the calciumantagonists but acts by mechanisms different from those of conventional calcium channel blockers, on the cerebral microcirculation were studied in rats using isolated and cannulated intracerebral (parenchymal) arterioles of 50 microns average diameter. After the vessels had developed spontaneous tone, increasing concentrations of HA1077 were applied extraluminally. HA1077 induced vasodilation in a dose-dependent manner with a maximal increase of vessel diameter of 73.9 +/- 5.1% (mean +/- SEM, n = 5) at 10(-4) M and with half-maximal responses (ED50) of 1.00 x 10(-6) M. The extent of maximal vasodilation achieved by HA1077 was significantly greater than that induced by such conventional calcium channel blockers as diltiazem, verapamil, nifedipine and nimodipine (about 50% each in a previous report from our laboratory). Vasoconstriction induced by synthetic thromboxane A2 (10(-9) M to 10(-5) M) which is through to be highly dependent on intracellular calcium, was completely inhibited by 10(-4) M HA1077, whereas both verapamil and nimodipine at a concentration at maximal vasodilation effects (10(-5) M and 10(-7) M respectively) only partially inhibited such vasoconstriction. These results suggest that HA1077 may exert a more potent vasodilator effect on the cerebral microcirculation than do conventional calcium channel blockers.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Meningitis in the neurosurgical patient.

In the patient with a basilar skull fracture and CSF leak, the risk of meningitis is greatly increased. The diagnosis of both leak and infection can be obscured by the patient's other injuries, and requires aggressive investigation of symptoms that suggest infection. Although the diagnosis is made with CSF cultures, when clinically suspected, treatment should begin after appropriate cultures have been obtained. Treatment should be directed against the most likely organisms, Streptococcus pneumoniae, Haemophilus influenzae, and the other organisms common to the upper respiratory tract. There are no good indications for prophylactic antibiotic usage in patients with known CSF leaks. The patient with a shunt or other CNS prosthetic device may have various manifestations of infection, depending on the type of device and its termination. Frank meningitis or ventriculitis is not always present. Diagnosis requires direct culturing of the shunt milieu, with the most frequent isolates being staphylococcal species and gram-negative enteric bacilli. The most effective therapy, for both eradication of the infection and minimization of the duration and morbidity of therapy, involves removal of the infected shunt, external drainage during parenteral antibiotic therapy, and complete replacement of hardware at the time of internalization. The postsurgical patient will not develop meningitis very frequently, but like the posttrauma patient, concurrent factors can make the diagnosis difficult. Differentiating infectious from chemical meningitis must often be initially based on CSF cell counts and chemistries alone. Treatment to cover the most likely organism, staphylococcal species and respiratory flora, should be started before the culture results are finalized.(ABSTRACT TRUNCATED AT 250 WORDS)

Central Nervous System↗

Effects of inhibitory and excitatory amino acid neurotransmitters on isolated cerebral parenchymal arterioles.

The vasoactive properties of inhibitory (gamma-aminobutyric acid (GABA), glycine) and excitatory (glutamate, aspartate) amino acid neurotransmitters were studied in isolated rat cerebral parenchymal arterioles. None of these neurotransmitters had a significant effect on vessel diameter at concentrations between 10(-9) and 10(-3) M, except for 10(-3) M glycine. These amino acid neurotransmitters are unlikely to play a role in regulation or pathophysiology of the cerebral microcirculation by directly changing vascular diameter.

Amino Acids↗

Effects of mannitol on intracerebral arteriolar diameter in vitro: extraluminal and intraluminal application.

The effects of mannitol on the cerebral microcirculation were studied using isolated perfused intracerebral (parenchymal) arterioles in rats. After vessels developed spontaneous tone, increasing concentrations of mannitol were applied extraluminally. Mannitol induced vasodilation in a dose-dependent manner. In an initial series of vessels, a 2% mannitol solution produced a maximal increase of vessel diameter of 35.8 +/- 2.2% (mean +/- SEM; n = 5). The degree of vasodilation was comparable to that produced by a sucrose solution of nearly equal osmolarity, suggesting that mannitol produced nonspecific vasodilation by increasing osmolarity. Organ bath solution pH was varied to 6.8 and 7.6 from the control pH of 7.3 in order to examine the effects of mannitol on vessels with different degrees of vessel tone. The mannitol dose-response curves in these vessels were parallel to each other, indicating that vasodilating effects of mannitol are essentially constant irrespective of the initial tone state of the vessel. In a second series of experiments, the effects of intraluminally applied mannitol on intracerebral arterioles were examined and compared to extraluminal application. Intraluminal application of 2% mannitol solutions produced a 42.6 +/- 2.0% (n = 5) increase in vessel diameter, which was not significantly different from that produced by extraluminal application (42.5 +/- 2.9%; n = 5; p = 0.89). Our results indicate that the direct action of mannitol on vascular smooth muscle in intracerebral arterioles is vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Calcium dependence of intracerebral arteriolar vasomotor tone and constrictor responses in rats.

The purpose of our study was to determine in rats the dependence of constrictor responses of intracerebral (parenchymal) penetrating arterioles on extracellular calcium. Vessel diameter was monitored in vitro, after spontaneous tone had developed. When the organ bat solution was changed from a physiological solution to a Ca2+-free one containing 0.5 mM EGTA, these vessels showed rapid and marked vasodilation to a mean +/- SEM of 159.8 +/- 8.2% of control (p = 0.018). After 3 minutes of pretreatment with Ca2+-free solution, constrictor responses to solutions of 140 mM KCl, pH 8.0, or 10(-4) M prostaglandin F2 alpha, were completely abolished, except for small transient contractions with the latter (6.6 +/- 1.8%). When vasoconstrictors were applied simultaneously with the Ca2+-free solution, all vessels still dilated to 159.8 +/- 8.4% (KCl), 146.7 +/- 6.1% (pH 8.0), and 124.3 +/- 9.1% (prostaglandin 2 alpha) of control (p = 0.018). Our results suggest that both vasomotor tone and constrictor responses in intracerebral arterioles are highly dependent upon activation from an extracellular calcium source.

Animals↗

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↗

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↗

Spontaneous tone of cerebral parenchymal arterioles: a role in cerebral hyperemic phenomena.

An isolated cerebral arteriole preparation was used to test the hypothesis that a temporary reduction in transmural pressure causes a subsequent vasodilation mediated by mechanisms intrinsic to the vessel wall. Thirty-five cerebral vessels of 44.7 +/- 1.4 microns (+/- standard error of the mean) mean diameter were cannulated in vitro and pressurized at a transmural pressure of 60 mm Hg: after an equilibration period the vessels developed spontaneous tone. When transmural pressure was decreased to 0 mm Hg for a period of 4 minutes then returned to 60 mm Hg, vessels dilated to 155.1% +/- 6.8% of control diameter before gradually redeveloping spontaneous tone in 5.5 +/- 0.7 minutes. Varying the duration of the period during which transmural pressure was at 0 mm Hg had no significant effect on the degree of vasodilation. Conversely, varying the level of decreased transmural pressure between 0 and 20 mm Hg significantly affected both the magnitude of vasodilation and the time course of spontaneous tone recovery. These findings indicate that a temporary period of decreased transmural pressure may result in a loss of spontaneous tone in the resistance vessels of the cerebral microcirculation. Mechanisms intrinsic to the vessel wall may play a significant role in the early stage of post-reperfusion hyperemia. Such mechanisms could also be implicated in other hyperemic phenomena affecting the cerebral circulation, such as the rapid increase in intracranial pressure after subarachnoid hemorrhage, the development of the normal perfusion pressure breakthrough phenomenon, and the initiation of intracranial pressure plateau waves.

Animals↗

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↗

Vasomotor responses of rat intracerebral arterioles to vasoactive intestinal peptide, substance P, neuropeptide Y, and bradykinin.

The effect of vasoactive peptides on vascular smooth muscle in the cerebral microcirculation was examined using an isolated intracerebral arteriole preparation. Extraluminally applied vasoactive intestinal peptide (VIP) dilated the spontaneous tone of intracerebral arterioles to 118.9 +/- 3.1% of control diameter at pH 7.30, with an EC50 of 7.27 X 10(-8) M. Similar degrees of dilation to VIP were seen in vessels preconstricted by changing bath solution to pH 7.60. Substance P had no effect on vessel diameter at pH 7.30. However, in vessels precontracted by pH 7.60, significant dose-dependent dilation was observed with an EC50 of 2.55 x 10(-10) M. Neuropeptide Y constricted intracerebral arterioles to 81.22 +/- 2.7% of control diameter, with an EC50 of 6.23 x 10(-10) M. Bradykinin dilated intracerebral arterioles at pH 7.30 and pH 7.60 to 130 +/- 3.0% of control diameter. VIP and bradykinin are potent vasodilators of intracerebral arterioles. Neuropeptide Y is a vasoconstrictor. The effect of substance P appeared to be either pH-dependent or dependent on some degree of precontraction by another agonist, but no effect on vessel diameter was seen at pH 7.30.

Animals↗