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Biomedical subjects

M C Wallace

Publications and source records attributed to M C Wallace.

At least 19 recordsLinked to original sources

C1-C2 posterior cervical fusion: long-term evaluation of results and efficacy.

Posterior wiring techniques are the most commonly used methods of achieving C1-C2 arthrodesis. Recently, transarticular screw fixation and interlaminar clamping have been advocated to achieve more secure fixation. A retrospective review of patients undergoing C1-C2 fusion for nonneoplastic disease was undertaken at the University of Toronto Hospital, with the aim of determining the long-term outcome of the selected procedures. Thirty-two patients underwent 36 procedures from 1986 to 1992, with a mean follow-up of 4.7 +/- 2.2 years (range, 2.0-8.0 yr). The most common disease processes were odontoid fracture (18 patients), transverse atlantal ligament injury (5 patients), os odontoideum (5 patients), and rheumatoid C1-C2 instability (3 patients). Thirty-one Gallie fusions, one Brooks-Jenkins fusion, two transarticular screw fusions, and two Halifax clamp applications were performed. Six (19%) of Gallie/Brooks-Jenkins fusions failed. These occurred with os odontoideum (three patients), Type II odontoid fracture (two patients), and transverse atlantal ligament injury (one patient). All transarticular screw and Halifax clamp procedures resulted in successful fusions. Two procedures (6%) resulted in new neurological deficit; both of these patients underwent posterior wiring for os odontoideum. This study suggests that Type II odontoid fractures may be successfully managed by a posterior wiring technique alone. Rheumatoid C1-C2 instability may be managed by posterior wiring supplemented with halo immobilization. Transarticular screw fixation has several potential advantages as a technique for C1-C2 arthrodesis and, in particular, may be appropriate for os odontoideum that had a high failure rate (75%) with conventional posterior wiring, even when this was supplemented with halo bracing.

Adolescent

Neutral red staining for the assessment of acute outcome in rat focal cerebral ischemia models.

Neutral red staining was evaluated as an acute outcome assessment method in rat models of cerebral ischemia by comparison with histological infarction volume. Fischer 344 rats (n = 48) were used in three different models of middle cerebral artery (MCA) occlusion: proximal MCA occlusion (n = 16), distal MCA occlusion followed by ipsilateral common carotid artery (CCA) occlusion (distal MCA/CCA occlusion, n = 15), and MCA occlusion with an intravascularly introduced 4-0 nylon suture (intravascular MCA occlusion, n = 17). At 1 hour, 2 hours, and 4 hours after MCA occlusion, animals were injected with 2.5 ml of 4% neutral red solution via the femoral vein, and then sacrificed. Proximal MCA occlusion caused a neutral red defect volume in the cortex which correlated well with histological infarction volume at 4 hours (r = 0.88, p < 0.05), and in the caudate which correlated well with infarction volume at 4 hours (r = 0.94, p < 0.01). Distal MCA/CCA occlusion caused a neutral red defect volume in the cortex lager than the histological infarction volume (4 hrs: 88.6 +/- 11.8 vs. 74.3 +/- 17.4 mm3, p < 0.05) but closely correlated with the infarction volume at 4 hours (r = 0.81, p < 0.05). Intravascular MCA occlusion caused a neutral red defect volume in only two of 17 animals after 1-4 hours, which correlated well with the absence of histological evidence of infarction. Neutral red staining is a simple method for assessing the acute outcome of focal cerebral ischemia as early as 4 hours after the onset, in an appropriate model of cerebral ischemia.

Animals

Pathological effects of angioplasty on vasospastic carotid arteries in a rabbit model.

To define the pathological effects of angioplasty on vasospastic arteries, 36 rabbits underwent angiography and induction of vasospasm by placement of blood-filled (vasospasm groups) or empty (control group) silastic sheaths around the cervical carotid arteries. Two (Day 2) or 7 days (Day 7) later, angiography was repeated and one carotid artery in each animal was dilated by balloon angioplasty. The rabbits were sacrificed 1 day, 7 days, or 3 to 4 weeks after angioplasty. Significant vasospasm developed after placement of silastic sheaths with blood (mean reductions in diameter 39% +/- 6% at Day 2 and 48% +/- 5% at Day 7). Arterial narrowing was less apparent in the control groups at Day 2 (24% +/- 7%). Angioplasty performed on Day 2 significantly increased arterial diameters of vasospastic arteries (50% +/- 7%; p < 0.05) but not those of control arteries (10% +/- 6%, p > 0.05). Angioplasty performed on Day 7 increased the arterial diameters by a similar degree (47% +/- 13%, not significant). Arteries remained dilated after angioplasty, although there was significant vasospasm 7 days after angioplasty when angioplasty was performed on Day 2. Blinded, semiquantitative histopathological study of the arteries showed that 3 to 4 weeks after angioplasty, there was significant endothelial proliferation and a trend for thinning of the tunica media. There were no significant changes in control arteries subjected to angioplasty. Angioplasty was not associated with significant arterial fibrosis as measured by hydroxyproline content (analysis of variance). The increase in endothelial proliferation and decrease in the thickness of the tunica media suggest that, in the rabbit model, angioplasty damages endothelial and smooth-muscle cells. This may be the basis for the observation that vasospastic arteries do not reconstrict after angioplasty.

Analysis of Variance

Bilateral third cranial nerve palsies in association with a ruptured anterior communicating artery aneurysm.

Third cranial nerve palsy occurring in a patient with an intracranial aneurysm is typically unilateral and associated with an internal carotid-posterior communicating or distal basilar artery aneurysm. In this report a patient with bilateral third cranial nerve palsies associated with rupture of an anterior communicating artery aneurysm is described. Raised intracranial pressure without brain herniation and compression of the third nerves within the perimesencephalic cisterns by focal subarachnoid clot are suggested as possible underlying mechanisms of the palsies, which showed complete recovery at 4 months after the hemorrhage and subsequent early aneurysm repair.

Carotid Artery, Internal

Surgical referral for carotid artery stenosis--the influence of NASCET. North American Symptomatic Carotid Endarterectomy Trial.

A retrospective review was undertaken of 139 consecutive patients with presumed carotid artery stenosis referred to a vascular neurosurgeon. The review period included three years prior and one year subsequent to the publication of the North American Symptomatic Carotid Endarterectomy Trial (NASCET) preliminary results showing surgery to be superior to best medical therapy for patients with symptomatic, high grade (> 70% linear diameter) carotid stenosis. The aims of this analysis were to determine any changes in the referral pattern following the NASCET publication (post-NASCET), and to examine the use and reliability for surgical decision making of pre-referral carotid artery imaging. Patient referral rate increased markedly post-NASCET, particularly from neurologists. There was a trend for more post-NASCET referrals to be for high grade stenosis and fewer referrals to be for intermediate grade (30-69% linear diameter) stenosis, although continued referral of patients with intermediate grade stenosis is desirable as randomization into NASCET continues for this group of patients. Ninety-six patients (69%) were referred with carotid duplex ultrasonography having been performed. There was poor correlation of these results with angiography, which remains necessary for planning management. A majority of patients (65%) referred to this surgical practice did not come to surgery.

Adult

Mechanism of action and persistence of neuroprotection by cell-permeant Ca2+ chelators.

Cell-permeant Ca2+ chelators such as 1,2-bis-(2-aminophenoxy)ethane- N,N,N',N'-tetraacetic acid acetoxymethyl ester (BAPTA-AM) have been reported to protect neurons in experimental focal cerebral ischemia. However, their in vivo actions are uncertain, and their protective efficacy is proven only in brief cerebral ischemia paradigms. Here we examine their mechanism of action in vitro and duration of efficacy in vivo. Electrophysiological studies were made in CA1 neurons in rat hippocampal slices. When superfused with BAPTA-AM (30-50 microM), CA1 somatic field potential recordings showed attenuation of the population spike amplitude, and intracellular recordings showed reduced excitatory postsynaptic potentials, indicating inhibition of excitatory synaptic transmission. Also, Ca(2+)-dependent accommodation and post-spike-train hyperpolarizations were reduced, indicating Ca2+ chelation hear the internal cell membrane surface. To determine whether Ca2+ chelators reduce the size of cerebral infarction rather than simply delaying its evolution, we studied the effects of BAPTA-AM treatment on infarction size 24 h after permanent middle cerebral artery occlusion. Fischer rats (n = 8 per group) were pretreated with saline, BAPTA-AM (20 mg/kg), or MK-801 (0.5 mg/kg). Infarction volumes in animals treated with BAPTA-AM were reduced by 50.5% compared with controls (p = 0.018), whereas animals treated with MK-801 experienced a statistically insignificant infarct volume reduction (26%; p = 0.27). These data show a persistence of neuroprotection by the Ca2+ chelator at 24 h and indicate that it may act by attenuating synaptic transmission and subplasma membrane Ca2+ excess.

Animals

Peri-operative anticoagulant effects of heparinization for carotid endarterectomy.

The question of whether or not to reverse heparin following carotid endarterectomy is a topic of debate. The potential reduction of the risk of thrombosis at the endarterectomy site with non-reversal has to be measured against a potential increase in the risk of wound haematoma. This study prospectively followed activated clotting time (ACT) of 42 consecutive patients undergoing carotid endarterectomy. A standard heparin dose of 100 units/kg was used, and heparin reversal was employed only if the wound appeared excessively haemorrhagic at the procedure's completion. Heparin was reversed in 11 patients. Following heparin administration, ACT increased to a mean 2.72 +/- 0.09 times baseline (range 1.84-4.07), and fell with time, until at 3 h after heparin administration mean ACT in the non-reversed patients was 1.48 +/- 0.03 times baseline (range 1.1-2.03). There was one postoperative neurological event (2%), a contralateral hemisphere stroke. No patient developed a frank wound haematoma requiring evacuation, although three patients (7% of the total study group, 9% of patients not receiving heparin reversal) developed neck swelling and symptoms of airway compromise, and were intubated. Measurements of ACT suggest that a heparin dose of 100 units/kg achieves an adequate anticoagulant level in the operative and early postoperative phase, when thrombosis is most likely to occur, and is not associated with an increased risk of wound haematoma. If heparin is to be selectively reversed in patients felt to be at high risk of postoperative haematoma, the decision should be based on an objective measurement such as ACT, and not the surgeon's impression of wound haemostasis.

Aged

A novel synapse-associated noncoding RNA.

Synaptic nuclei of innervated muscle transcribe acetylcholine receptor (AChR) genes at a much higher level than extrasynaptic nuclei. To isolate candidate synaptic regulatory molecules responsible for the unique transcriptional potential of synaptic nuclei, we have taken a subtractive hybridization approach. Here, we report the cloning and characterization of a novel synapse-associated RNA, 7H4. 7H4 is expressed selectively in the endplate zone of skeletal muscle and is upregulated during early postnatal development and after denervation. Interestingly, the 7H4 gene has no introns, and yet two different-size RNAs with identical polyadenylated 3' ends are generated. Most intriguingly, the nucleotide sequence does not contain any significant open reading frames, suggesting that 7H4 may function as a noncoding RNA.

Animals

The effect of surgery on the severity of vasospasm.

Intracranial aneurysm surgery performed between 4 and 12 days after subarachnoid hemorrhage (SAH) has been associated with an increased risk of delayed cerebral ischemia and poor outcome compared to surgery performed before or after this time. To investigate whether this increased risk is due to aggravation of vasospasm, the angiograms obtained before and after surgery in 56 patients operated on at various times after aneurysmal SAH were studied. Vasospasm was quantitated by measuring the diameters of intracranial arteries and expressed as the ratio of the diameters of the intracranial arteries to the diameter of the extracranial internal carotid artery. Aggressive surgical clot removal was not performed at surgery. To correct for differences in prognostic factors for vasospasm between patients operated on at different times after SAH, multiple regression analysis was performed using the arterial diameter ratio during vasospasm as the dependent variable and the prognostic factors for vasospasm, including the time of surgery, as independent variables. Equations predicting the severity of vasospasm could be generated using the clinical grade on admission, patient age, and preoperative arterial diameter ratio. The time of surgery had no effect on vasospasm. Cerebral infarction due to vasospasm developed in five (15%) of 34 patients operated on within 3 days after SAH and in four (20%) of 20 operated on between 4 and 12 days after SAH (p = 0.66). A good outcome for these two groups was achieved in 88% and 85%, respectively (p = 1.00). These results suggest that the timing of surgery does not affect the development of vasospasm. Any increased risk of cerebral ischemia associated with surgery performed between 4 and 12 days after SAH is due to factors other than aggravation of vasospasm.

Adult

Rotational angiography assessment of cerebral aneurysms.

PURPOSE: To compare rotational angiography with conventional digital subtraction angiography in the assessment of cerebral aneurysms. METHODS: Conventional digital subtraction angiography and rotational angiography were compared in 57 patients investigated for the preoperative diagnosis of subarachnoid hemorrhage and in 13 patients after surgery. Images were compared for location, visibility of the aneurysmal neck, vascular branch anatomy, projection, size, presence of spasm, and shape of the aneurysm. RESULTS: Rotational angiography was superior to the digital angiogram in assessing aneurysms and vascular anatomy in the following percentage of cases: 12% for location, 46% for the presence of a neck, 32% in the assessment of branch anatomy, 19% for projection, 12% for size, 3.5% for spasm, and 19% for shape. After surgery, rotational angiography more clearly demonstrated the presence or absence of a neck in 69% of the cases. CONCLUSIONS: Rotational angiography often allows better visualization of vascular anatomy and therefore improves the angiographic assessment of aneurysms when compared with conventional digital subtraction angiography, making it an excellent adjunct in the investigation of subarachnoid hemorrhage. The lack of subtraction artifacts from the surgical clips and multiple angles of view also allow better assessment of the presence or absence of a residual neck in postoperative cases.

Angiography, Digital Subtraction

Percutaneous transluminal angioplasty for cerebral vasospasm after subarachnoid hemorrhage.

OBJECTIVE: To assess the efficacy of percutaneous transluminal angioplasty. DESIGN: A retrospective case study covering the period January 1990 to December 1992. SETTING: A tertiary-care referral centre. PATIENTS: Thirteen patients, ranging in age from 23 to 57 years, who had suffered an aneurysmal subarachnoid hemorrhage and subsequent symptomatic vasospasm that had not responded to aggressive medical therapy. INTERVENTION: Percutaneous transluminal angioplasty of spastic cerebral arteries MAIN OUTCOME MEASURES: Neurologic improvement (improved level of consciousness or resolution of focal deficit) immediately after angioplasty and functional status at 6 months after angioplasty. RESULTS: Four (31%) patients showed neurologic improvement immediately after angioplasty. At 6 months, 5 (38%) of the 13 were independent, 2 (15%) were dependent (severely disabled), and 6 (46%) had died. Poor clinical grade at the time of angioplasty was associated with a poor outcome. CONCLUSIONS: Percutaneous transluminal angioplasty appears to be a safe procedure that is beneficial in some patients with symptomatic vasospasm refractory to aggressive hypervolemic, hypertensive therapy. The best results likely are obtained in patients of good clinical grade in whom new neurologic deficits have not become established, and angioplasty should not be delayed if medical therapy does not rapidly reverse the symptoms of vasospasm.

Adult

Venous congestion: an MR finding in dural arteriovenous malformations with cortical venous drainage.

PURPOSE: To present the MR findings of intracranial dural arteriovenous malformations with cortical venous drainage, emphasizing the parenchymal changes. METHODS: Conventional MR and x-ray angiograms in 13 patients with dural arteriovenous malformations and cortical venous reflux were reviewed. The site of the shunt, location of the venous reflux, and presence of venous stenosis were assessed on the angiograms. Parenchymal changes, dilated vessels, and venous occlusive disease were assessed on MR. RESULTS: On MR, 10 of the 13 patients (77%) had dilated pial vessels. Two patients had hydrocephalus. Two patients presented with parenchymal bleeds, one with a subdural component, both remote from the nidus. Two patients presented with subarachnoid hemorrhage. One patient had a parenchymal bleed 9 months after presentation. Venous occlusion was evident on MR in 2 patients. Diffuse white matter edema in the cerebellar or cerebral hemispheres was present on MR in 4 patients and correlated with neurologic deficits. In 2 of these 4 patients, gadolinium enhancement was seen in the periphery of the involved hemisphere. CONCLUSIONS: On MR a surplus of pial vessels suggests a dural arteriovenous malformation with cortical venous drainage. The MR finding of white matter edema deep in the cerebral or cerebellar hemispheres is direct evidence of a venous congestion.

Adult

Separable regulatory elements governing myogenin transcription in mouse embryogenesis.

Expression of the myogenic helix-loop-helix (HLH) protein myogenin in muscle cell precursors within somites and limb buds is among the earliest events associated with myogenic lineage determination in vertebrates. Mutations in the myogenin promoter that abolish binding sites for myogenic HLH proteins or myocyte enhancer factor-2 (MEF-2) suppressed transcription of a linked lacZ transgene in subsets of myogenic precursors in mouse embryos. These results suggest that myogenic HLH proteins and MEF-2 participate in separable regulatory circuits leading to myogenin transcription and provide evidence for positional regulation of myogenic regulators in the embryo.

Animals

Cell-permeant Ca2+ chelators reduce early excitotoxic and ischemic neuronal injury in vitro and in vivo.

We report the characterization of the first successful treatment of neuronal ischemic injury in vivo by cell-permeant Ca2+ chelators. The chelators attenuated glutamate-induced intracellular Ca2+ increases and neurotoxicity in neuronal explant cultures. When infused intravenously in rats, permeant fluorescent BAPTA analogs accumulated in neurons in several brain regions. BAPTA-AM, infused in vivo, reduced Ca(2+)-dependent spike frequency adaptation and post-spike train hyperpolarizations in CA1 neurons taken from treated animals. This effect was reproduced by direct injections of BAPTA into untreated neurons. The effects of three different chelators (BAPTA, 5,5'-difluoro BAPTA, and 4,4'-difluoro BAPTA) on Ca(2+)-dependent membrane excitability varied with their Ca2+ affinity. When the chelators' permeant forms were used to treat rats prior to the induction of focal cortical ischemia, they were highly neuroprotective, as gauged by significant reductions in cortical infarction volumes and neuronal sparing. The chelators' protective effects in vivo also reflected their affinity for Ca2+. This report provides the most direct evidence to date that intracellular Ca2+ excess triggers early neurodegeneration in vivo and contributes a novel therapeutic approach to neuronal ischemia of potential clinical utility.

Animals

The 48-month increment of root caries in an urban population of older adults participating in a preventive dental program.

The purpose of this study was to determine the effect of a 48-month preventive dental program on the incidence of root caries in an urban, geriatric, noninstitutionalized population residing in an optimally fluoridated area. The 466 participants were randomly assigned to one of three groups at baseline. Group A (control): 171 subjects using a placebo mouthrinse daily; group B: 147 subjects receiving semiannual applications of a topical APF gel (1.2% F-) with the daily use of a placebo mouthrinse; group C: 148 subjects using a fluoridated mouthrinse daily, ACT (0.05% F-). At baseline, the numbers of surfaces at risk, and decayed and filled surfaces were recorded. After 48 months, in addition, the number of reversed and new lesions were determined, and the incremental DMFS calculated. The data were analyzed by ANCOVA. The incremental DMFS were: A = 0.91, B = 0.27, C = 0.26. The incremental DMFS in groups B and C were significantly lower than in group A (P < .05). The number of reversed lesions in group C (1.53 +/- 2.03) was significantly greater than in group A (1.11 +/- 1.74) and group B (1.01 +/- 1.86) (P < .05). The number of new lesions in group B (1.36 +/- 2.00) was significantly less than in group A (1.99 +/- 2.65) (P < .05). The daily use of the fluoride mouthrinse significantly increased the number of reversed lesions.

Acidulated Phosphate Fluoride

Role of angiography following aneurysm surgery.

The postoperative angiograms in 66 patients who underwent craniotomy for clipping of 78 cerebral aneurysms were reviewed. Indications for urgent postoperative angiography included neurological deficit or repeat subarachnoid hemorrhage. Routine postoperative angiograms were carried out in the remaining patients. Postoperative angiograms were reviewed to determine the incidence of unexpected findings such as unclipped aneurysms, residual aneurysms, and unforeseen major vessel occlusions. Logistic regression analysis was used to test if the following were factors that predicted an unexpected finding on postoperative angiography: aneurysm site or size; the intraoperative impression that residual aneurysm was left or a major vessel was occluded; intraoperative aneurysm rupture; opening or needle aspiration of the aneurysm after clipping; or development of a new neurological deficit after surgery. Kappa values were calculated to assess the agreement between some of these clinical factors and unexpected angiographic findings. Unexpected residual aneurysms were seen in three (4%) of the 78 occlusions. In addition, three aneurysms were completely unclipped (4%); these three patients were returned to the operating room and had their aneurysms successfully obliterated. There were nine unexpected major vessel occlusions (12%); six of these resulted in disabling stroke and two patients died. Of six major arteries considered to be occluded intraoperatively and shown to be occluded by postoperative angiography, two were associated with cerebral infarction. Logistic regression analysis showed that a new postoperative neurological deficit predicted an unforeseen vessel occlusion on postoperative angiography. Factors could not be identified that predicted unexpected residual aneurysm or unclipped aneurysm. The inability to predict accurately the presence of residual or unclipped aneurysm suggests that all patients should undergo postoperative angiography. Since a new postoperative neurological deficit is one factor predicting unexpected arterial occlusion, intraoperative angiography may be necessary to help reduce the incidence of stroke after aneurysm surgery. With study of more patients or of factors not examined in this series, it may be possible to select cases more accurately for intraoperative or postoperative angiography.

Adult