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Biomedical subjects

B Weir

Publications and source records attributed to B Weir.

At least 73 records · Page 4Linked to original sources
PubMed1988

Factors influencing the outcome of aneurysm rupture in poor grade patients: a prospective series.

When is the outlook hopeless after rupture of an intracranial aneurysm? Some data bearing on the answer to this important question were obtained in a prospective, multicenter trial of 184 poor grade patients in a study of the calcium antagonist nimodipine. Entry was within 3 days of subarachnoid hemorrhage (SAH). The admission work-up included angiography of the anterior and posterior circulations and computed tomographic (CT) scans. The angiograms were repeated as close to Day 8 post-SAH as possible, and the CT scans were repeated at 3 months at the time of follow-up neurological assessment. Radiological assessment was performed independently of knowledge of drug treatment or patient outcome. A discriminant function analysis indicated that the relative importance of factors prognostic for outcome was, in order of importance: whether the patient was treated surgically, neurological grade on admission, age, initial systolic blood pressure, and aneurysm size. The discriminant function analysis correctly classified 80% of our cases. A constellation of poor prognostic features will aid the neurosurgeon in treating a patient conservatively and appropriately advising relatives. The ultimate decision on how to treat a given patient continues to depend partly on clinical judgement, which remains intuitive and subject to influences not studied here.

Adolescent↗
PubMed1987

The management of .22 caliber gunshot wounds of the brain: a review of 49 cases.

We analyzed the charts and CT scans of 49 cases of civilian .22 caliber gunshot wounds of the brain admitted to the University of Alberta and Royal Alexandra Hospitals between 1975 and 1985. The average age of the patients was 30 years, 88% were males, 88% were suicide attempts. There were no deaths among patients with an initial coma score above 12 whereas the mortality rate was 85% for those admitted with a score of 7 or less. All those with fixed pupils on admission died. The overall mortality rate of 61% is comparable to that of other series of civilian gunshot wounds including those in which more aggressive surgical management was undertaken. We recommend that no treatment be given those cases with an admission coma score of 3 and/or fixed pupils and that simple scalp wound debridement be employed with those having a coma score of 7 or less. Tract exploration and retrieval of bullet fragments is not indicated, as retained fragments carry a very low incidence of complications (e.g. abscess formation). In patients in good condition (GCS greater than or equal to 12) the management of intracranial hematomas should be independent of their etiology and approached aggressively.

Adolescent↗
PubMed1987

Hydrocephalus following aneurysmal subarachnoid haemorrhage.

Ninety-four patients with hydrocephalus following subarachnoid haemorrhage were investigated. Fourteen of these patients had temporary ventricular drains inserted, 19 had drains that were later converted to ventricular-peritoneal shunts, and 61 patients had shunts only. All patients were analysed with respect to their grade on admission, the distribution of blood on CT scan, their Glasgow Coma Score, their intracranial pressure, and the presence or absence of vasospasm on angiography. Outcome was analysed by shunt procedure and time of shunt insertion. The higher the grade on admission, the more likely it was the patient would require a shunt. Fewer patients with a good outcome required shunting as compared to those whose outcome was poor. Patients having more subarachnoid blood on CT scan tended to present with a lower Glasgow Coma Score. The outcome of patients with intraventricular haemorrhage was not obviously influenced by the insertion of a ventriculostomy. Vasospasm was not more common in patients requiring a ventriculo-peritoneal shunt, nor did early shunting in patients with hydrocephalus affect the incidence of vasospasm. The majority of patients were either shunted in the first three days or after 30 days post-SAH. The outcome was better in those patients shunted at a later date.

Acute Disease↗
PubMed1987

Effect on management mortality of a deliberate policy of early operation on supratentorial aneurysms.

Of 736 patients with intracranial aneurysms seen at the University of Alberta from 1968 to 1985, 437 were admitted on the day of or the day after subarachnoid hemorrhage (SAH) from a supratentorial aneurysm. Of these, 205 were managed from 1968 through 1977 and 232 were managed from 1978 through early 1985 after a policy of early aneurysm operation had been implemented. Postoperative and management mortality and morbidity rates were related to the grade of the patient at the time of admission and the time interval before operation. Overall management mortality (and postoperative mortality) rates for patients treated before 1978 were 47% (19%) for all grades, 17% (12%) for Grades 1 and 2, 51% (25%) for Grades 3 and 4, and 100% (100%) for Grade 5. Since 1978, mortality has been reduced to 38% (11%) for all grades, 10% (5%) for Grades 1 and 2, 39% (17%) for Grades 3 and 4, and 96% (60%) for Grade 5. Management mortality for patients operated on Day 0 to 3 was lower than for those operated later after SAH both before and after 1978. Postoperative mortality was lowered in all patients operated from 1978 to 1985 regardless of the interval from SAH to operation, and management mortality was reduced overall, as well as for patients operated on day 0 to 3, in those treated from 1978 to 1985. The authors conclude that a policy of early aneurysm operation has contributed to a reduction of both postoperative and management mortality.

Adult↗
PubMed1987

Different distributions of substance P and vasoactive intestinal polypeptide in the cerebral arterial innervation in rat and guinea pig.

In immunofluorescence studies, nerve fibers containing substance P were sparse and limited to the anterior and middle cerebral arteries in rats but in moderate supply and associated with all of the major cerebral arteries in guinea pigs. Fibers containing vasoactive intestinal polypeptide (VIP) were abundant in the rostral part of the circle of Willis in both species; moderate numbers were seen in the basilar and vertebral arteries in rats, but few in the rostral half of the basilar arteries and none in the caudal half of the basilar and vertebral arteries in guinea pigs. These differences in distribution in the 2 rodents indicate wide variation in peptide-containing nerves around cerebral vasculature and preclude interspecies extrapolation of findings.

Animals↗
PubMed1986

Pathway of acetylcholinesterase containing nerves to the major cerebral arteries in rats.

The pathway of nerves containing acetylcholinesterase (AChE) to the major cerebral arteries was investigated in the rat. In this species, the internal ethmoidal artery (IEA) arises from the anterior cerebral artery (ACA) and anastomoses with the external ethmoidal artery (EEA), forming the ethmoidal rete on the cribriform plate. The ethmoidal nerve (EN) and EEA enter the cranial cavity through the ethmoidal foramen. Densely distributed adventitial nerve plexi were present around the IEA, ethmoidal rete, and EEA. Many thick nerve bundles were found in the periadventitial layers in association with these vessels. Around the EN, just before it enters the ethmoid foramen, intensely staining nerve bundles were present that entered the cranial cavity with the EN. After unilateral section of the EN and EEA, a marked decrease of the nerve fibers was observed around the arteries of the anterior part of the circle of Willis on the operated side, whereas the basilar artery (BA) showed a moderate decrease in the AChE activity. After bilateral section of the EN and EEA, nerves disappeared from around all the major cerebral vessels including the BA. Section of the EEA alone did not produce any visible change of the cerebral perivascular innervation. The present study suggests that AChE-containing nerves on the cerebral arteries arise from the AChE-positive nerve bundles, which enter the cranial cavity with the EN through the ethmoid foramen; The anterior part of the circle of Willis is innervated unilaterally by the AChE-positive nerve bundles from the ethmoidal foramen, whereas the BA receives bilateral innervation.

Acetylcholinesterase↗
PubMed1986

Thermodilution cardiac output--an in vitro model of low flow states.

The accuracy and reproducibility of thermodilution cardiac output measurements were examined in vitro at low flows, using the Edwards cardiac output computer. For each of 18 different volumetrically measured flows between 130 and 1035 ml/min, three cardiac outputs were determined for each of four different injectate volumes (1,2,3, and 5 ml) at two different temperatures (0 degrees C and room temperature). There was a significant (p less than .001) correlation between measured flow and cardiac output for all injectate volumes at both temperatures. The slopes of the regression lines ranged between 0.97 and 1.25, and the y-intercepts were all greater than 0. Although this thermodilution technique overestimated cardiac output, it was a reproducible means of measuring cardiac output in this low-flow in vitro model.

Cardiac Output↗
PubMed1986

Acute cardiopulmonary effects of subarachnoid hemorrhage in monkeys.

Twenty-eight cynomolgus monkeys had an autologous subarachnoid blood clot placed in the basal cisternae via craniectomy. Twenty-three monkeys survived clot placement and five animals died within 24 h. An additional eight monkeys underwent sham procedures and six acted as anesthetic controls. Cardiopulmonary indices were measured before clot placement and 30 to 60 min thereafter, to determine if certain changes had prognostic value for immediate outcome. In the 24-h survivors, heart rate and arteriovenous oxygen content difference increased significantly (p less than .05 and .01, respectively), while stroke index (SI) (p less than .01), mean pulmonary artery pressure (p less than .001), pulmonary artery wedge pressure (p less than .001), and central venous pressure (p less than .05) fell. In the 24-h nonsurvivors, cardiac index (CI) (p less than .05) and SI (p less than .01) fell to an even greater extent than in the survivors. There was a significant (p less than .05) difference between the two groups for CI and SI. There were no significant differences in the sham-operated animals. In six control monkeys, neither heart rate nor CI significantly increased throughout 5 h of anesthesia.

Animals↗
PubMed1986

Nimodipine and chronic vasospasm in monkeys: Part 3. Cardiopulmonary effects.

A subarachnoid hemorrhage was induced in 30 cynomolgus monkeys by the placement of a 6- to 7-ml blood clot through a frontotemporal craniectomy (Day 0). The monkeys underwent a 1-week-long, randomized, blind trial comparing various doses of nimodipine to placebo, sham, and no treatment. The treatment groups were: nimodipine, 3 mg/kg every 8 hours (n = 6), 6 mg/kg every 8 hours (n = 6), and 12 mg/kg every 8 hours (n = 6); placebo (polyethylene glycol 400), 0.33 ml/kg every 8 hours (n = 6); and no treatment (n = 6). An additional sham group underwent craniectomy without clot placement (n = 6) so that 36 animals in total were operated upon. Differences in cardiopulmonary indices between Day 0 and Day 7 were compared within and between groups. No significant differences were obtained in the sham and no treatment groups. The nimodipine 6- and 12-mg/kg groups showed significant decreases in blood pressure (P less than 0.04 and P less than 0.015). Systemic vascular resistance was increased in the placebo and 3-mg/kg groups (P less than 0.02) and decreased in the 12-mg/kg group (P less than 0.015). Stroke index was increased in the 12-mg/kg group (P less than 0.05). Cardiac index and stroke index correlated positively with nimodipine dosage (r = 0.99, P less than 0.05). There were no pronounced changes in pulmonary artery wedge pressure, central venous pressure, alveolar-arterial oxygen pressure difference, arteriovenous oxygen content difference, and percentage of shunting.

Animals↗
PubMed1986

Electron microscopy of simian cerebral arteries after subarachnoid hemorrhage and after the injection of horseradish peroxidase.

A large unilateral subarachnoid hemorrhage (SAH) was created in 21 monkeys, and horseradish peroxidase (HRP) was injected into the cisterna magna or left internal carotid artery in 3 others (normals). Cerebral fixation was performed on Day 14 after SAH or 15 minutes after HRP injection. The major cerebral arteries from both the nonclot (control) and clot sides and the normal animals were examined with scanning and transmission electron microscopy (SEM and TEM). SEM of the adventitial surfaces of control and normal arteries revealed tunnel-like structures along the longitudinal axis. No vasa vasorum were seen, but adventitial rounded openings were observed, 10 to 35 micron in diameter in vessels of the anterior circulation and up to 80 micron in diameter in the basilar arteries. The stomas, numbering 5 to 10/mm of specimen, appeared to connect the subarachnoid and intraadventitial spaces or pathways. In SAH arteries, the tunica adventitia was coated with cellular remnants of hematoma or dense, well-organized blood clots, the removal of which revealed blocked stomas. TEM showed HRP in the vessel walls after injection into the cisterna magna, but not after injection into the carotid artery. TEM of control arteries revealed Virchow-Robin (intraadventitial) spaces lined by simple planar epithelium-like cells; Virchow-Robin spaces contained sparse nerve fiber bundles and connective tissue fibers. In SAH arteries, these spaces were almost filled with strands of connective tissue and fibroblasts; no nerve fibers were detected. Vasogenic substances probably reach smooth muscle cells via the adventitial stomas. SAH occluding the stomas may block the cerebrospinal fluid circulation, disturbing nutrition of the arterial wall or removal of wastes from it, thereby aggravating vasospasm.

Animals↗
PubMed1986

Cerebral perivascular nerves in subarachnoid hemorrhage. A histochemical and immunohistochemical study.

The authors have studied the changes induced by subarachnoid hemorrhage (SAH) in the density and distribution of cerebral perivascular nerves in monkeys and rats. The SAH was induced in monkeys by placement of an autologous blood clot after opening the basal cisterns over the arteries of the circle of Willis on one side. In the rat study, SAH was induced by injection of autologous arterial blood into the cisterna magna. The nerves examined were adrenergic nerves, acetylcholinesterase (AChE)-containing nerves, vasoactive intestinal polypeptide (VIP)-like immunoreactive nerves, and substance P-like immunoreactive nerves. In the monkey study, all animals underwent baseline cerebral angiography, then had repeat angiography just before sacrifice on Day 2, 7, 28, or 70 after SAH. Two sham-operated monkeys underwent the surgical procedure without clot placement and were sacrificed on postoperative Day 7, after repeat angiography. Clot placement in monkeys reduced staining of all middle cerebral artery (MCA) perivascular nerves for between 2 and 28 days post-SAH. The number of stained nerve fibers of MCA's on the non-operated side was slightly reduced on Days 2 and 7 after SAH. Sham-operated monkeys showed a mild reduction of staining in all nerves, but only on the operated side. Cerebral vasospasm was observed on all angiograms taken on Days 2 and 7 following SAH. No vasospasm was found in normal or sham-operated monkeys. The disappearance of nerve staining without associated vasospasm was found on the operated side of the sham-operated monkeys and on the clot side of the animal sacrificed on Day 28 after SAH. Rats sacrificed on Days 2 and 7 post-SAH showed reduction in adrenergic and VIP-like immunoreactive staining around basilar arteries, while nerves containing AChE were not affected. Saline-injected rats exhibited no change in the appearance of perivascular innervation. These results suggest that SAH as well as surgical manipulation of the vessel wall caused a reduction of the studied substances in cerebral perivascular nerves. This reduction in immunoreactive staining of perivascular nerves did not correlate with the development of angiographic vasospasm after SAH.

Animals↗
PubMed1985

End-to-end transcription of an Alu family repeat. A new type of polymerase-III-dependent terminator and its evolutionary implication.

Four or more consecutive thymidine residues on the non-template strand and G + C-richness of flanking DNA are the two necessary characteristics of efficient RNA polymerase-III-dependent transcriptional terminators. We have identified, from the study of in vitro transcription of a human Alu family repeat, a new type of RNA polymerase-III-dependent transcriptional terminator. A 258 base-pair Alu repeat located on the 3' side of the human alpha 1 globin gene can be transcribed in a HeLa S-100 extract to generate three RNA species of lengths 404 to 408, 252 to 255 and 173 to 174 nucleotides, respectively. Kinetics, pulse-chase and RNA incubation experiments showed no significant internal processing of the longer transcripts into shorter ones. These data plus detailed RNA mapping demonstrated conclusively that the multiple Alu RNA species resulted from accurate initiation at the first base (5' end) of the repeat, and multiple termination downstream. The 3' end(s) of the major transcript (252 to 255 nucleotides) maps at the 3' end of the Alu repeat sequence where there are not four or more consecutive thymidine residues on the non-template strand. The functional domain of the terminator has been mapped to a 45 base-pair segment that includes 36 base-pairs of the 3' end sequence of the Alu repeat plus nine base-pairs downstream. The high efficiency of termination (greater than 90%), the lack of consecutive T residues, the richness in A + T content, and the proposed ability of the RNA to form an imperfect hairpin structure in the 3' region of the transcript, thus identify a new type of eukaryotic class III terminator. We compare the structure of this class III terminator with that of the bacterial rho-dependent terminator. We also discuss its implication in the mechanism(s) of amplification and dispersion of Alu sequences in the primate genomes.

Base Sequence↗
PubMed1985

Nimodipine and chronic vasospasm in monkeys: Part 1. Clinical and radiological findings.

The efficacy of the calcium channel blocker nimodipine in the prevention of chronic cerebral vasospasm (VSP) and delayed ischemia after subarachnoid hemorrhage (SAH) in monkeys was examined in a blind, randomized, placebo-controlled trial. The primate model developed in this laboratory reliably induces chronic cerebral vasospasm and can induce pathologically proven delayed ischemic neurological deficits (DINDs). With standard microsurgical procedures, an average 6.4-ml autologous hematoma was placed directly against the major anterior cerebral vessels in the right basal subarachnoid spaces of 24 monkeys. The monkeys were randomized to one of four groups and were treated orally q8h for 7 days with nimodipine (3, 6, or 12mg/kg)or placebo. An additional 2 monkeys underwent the surgical procedure without clot placement. Drug administration began between 14 and 20 hours after clot placement. Indices monitored before and after SAH included neurological status, angiographic cerebral vessel caliber, and cerebral blood flow. Significant VSP (25 to 100% reduction in vessel caliber) was present on Day 7 on the clot side in 83% of the animals (P less than or equal to 0.001). There was no significant difference (P greater than 0.05) in the incidence of VSP among the four groups. Similarly, there was no significant difference (P greater than 0.05) in the mean vessel caliber reduction after SAH among the four treatment groups. There was no VSP present on Day 7 in the sham-operated animals. One animal receiving high dose nimodipine (12 mg/kg p.o. q8h) developed a DIND on Day 5 after SAH. A second animal in the 12-mg/kg group developed a transient neurological deficit between Days 4 and 7.

Animals↗
PubMed1985

Nimodipine and chronic vasospasm in monkeys: Part 2. Pharmacological studies of vessels in spasm.

The effect of nimodipine on the in vitro reactivity of cerebral vessels after subarachnoid hemorrhage (SAH) was studied. With the use of a primate model of chronic cerebral vasospasm, 12 female cynomolgous monkeys underwent the induction of a SAH by the direct placement of an average 6.4-ml autologous hematoma against the major anterior cerebral vessels in the right basal subarachnoid spaces (Day 0). The animals were then randomized to one of four groups and within 14 to 20 hours after clot placement were started on oral q8h therapy with nimodipine (3, 6, or 12 mg/kg) or placebo. On Day 7, the animals were killed and the right and left middle cerebral arteries (MCAs) were immediately resected and placed in oxygenated Krebs' solution. Ring preparations from the arteries were suspended in organ baths, and dose-effect curves to varying concentrations of norepinephrine, 5-hydroxytryptamine, and potassium chloride were obtained. There was a highly significant reduction in the response of the MCA on the clot side (right) relative to the nonclot side (left) to all three agonists. The clot side contractility was not influenced by nimodipine treatment at any of the four doses tested. The nonclot side arteries of the 12-mg/kg treatment group demonstrated significantly enhanced reactivity for all three agonists. Oral treatment with high dose nimodipine enhances the reactivity of normal cerebral vessels to the agonists tested, but it does not seem to affect the reactivity of arteries in chronic spasm at any of the four doses tested.

Animals↗
PubMed1984

Rupture of an experimentally induced aneurysm in a primate.

Cerebral aneurysms are extremely rare in all animals except man. We report the occurrence of a carotid-ophthalmic aneurysm in a cynomolgous monkey two months following accidental occlusion of the ipsilateral cervical internal carotid artery. This was documented angiographically. The aneurysm was deliberately ruptured by the insertion and withdrawal of fine needles. This produced a large subarachnoid hemorrhage visualized on CT scan. There was a progressive severe fall in cerebral blood flow and moderate vasospasm. The neurological status deteriorated on the tenth day and the animal was sacrificed on day 13. On electron microscopy, the aneurysm showed a fibrous wall, and the endothelium showed balloon-like endothelial cells with gaps. Corrugations occurred in the inner aspect of the anterior circulation arteries.

Animals↗
PubMed1984

Calcium antagonists, cerebral ischemia and vasospasm.

The past fifteen years has seen the classification of diverse substances into a group known as calcium antagonists (CAs). They have a common ability to reduce the transmembrane transport of extracellular calcium ions (CAe2+). This flow of calcium into vascular smooth muscle is ultimately associated with the development of tension and vasoconstriction. Some CAs appear to have a predilection for cerebral as opposed to systemic arteries and so may function as specific cerebral arterial vasodilators. It has been proposed that they might be useful in certain types of cerebral ischemia such as that due to arterial occlusion or prolonged vasoconstriction. Animal experiments and initial clinical trials give grounds for cautious optimism that CAs may become as useful in neurology as they have recently become in cardiology.

Animals↗
PubMed1984

Management of acute subdural hematomas from aneurysmal rupture.

Subdural hematomas (SDH) from ruptured aneurysm (RA) are much less common than intracerebral (ICH) hematomas or subarachnoid (SAH) or intraventricular hemorrhage (IVH). With computerized tomography, preoperative diagnosis is now made more often. The authors have collected 18 such cases from a review of 897 cases of RA admitted to eleven medical centers in 1980 and 1981. Nine (50%) of these patients died prior to discharge from hospital. Four (22%) had surgery and died postoperatively and 9 (50%) were operated upon and survived. Thirteen (72%) of the patients showed anisocoria, decreased consciousness and unilateral weakness prior to surgery. Eight (89%) of the fatalities had shown preoperative herniation as opposed to only 5 (56%) of the survivors. The overall incidence of delayed ischemia due to vasospasm was 11% (2 cases). Those who died had greater midline shift and larger SDH on the admission CT scan. Sixteen (89%) of these patients were female. Thirteen (72%) had ruptured aneurysms on the internal carotid artery. All of these hematomas were unilateral and uniformly hyperdense, and the convexity hematomas were crescentic in shape. Seventeen (94%) had evidence of blood in locations other than the subdural space. If the patient is potentially salvageable and has a midline shift, the SDH should probably be evacuated immediately and the aneurysm clipped at the same operation since the development of a tentorial herniation has such an adverse effect on outcome.

Acute Disease↗