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Biomedical subjects

Richard E Clatterbuck

Publications and source records attributed to Richard E Clatterbuck.

At least 19 recordsLinked to original sources
PubMed2006

Intracranial delivery of the nitric oxide donor diethylenetriamine/nitric oxide from a controlled-release polymer: toxicity in cynomolgus monkeys.

OBJECTIVE: Diethylenetriamine/nitric oxide (DETA/NO) has been shown to be an effective treatment for delayed posthemorrhagic vasospasm when released abluminally from ethylene-vinyl acetate copolymer (EVAc). However, the observed mortality associated with this drug warrants further investigation. To establish a maximum tolerable dose, this study evaluated the toxicity of DETA/NO released from EVAc in a dose-escalation series in cynomolgus monkeys (Macaca fascicularis). METHODS: DETA/NO was incorporated into EVAc at a 20:80 dry weight ratio (DETA/NO:EVAc). A total of 13 animals underwent a right frontotemporal craniotomy for placement of a single polymer delivering no drug (n = 3), 0.5 +/- 0.1 mg/kg (n = 3), 0.9 +/- 0.1 mg/kg (n = 3), 1.9 +/- 0.2 mg/kg (n = 3), or a 3.2 mg/kg dose (n = 1) into the subarachnoid space. RESULTS: The animal receiving the highest dose of DETA/NO (3.2 mg/kg) died 46 hours after surgery. The remaining animals survived for the planned duration of the study. One animal in the group receiving the 1.9 mg/kg dose experienced a seizure 25 hours after surgery and remained lethargic for 2 days before making a complete recovery. The remaining animals exhibited no adverse behavioral effects. Histopathological examination of brain tissue revealed hemorrhagic and ischemic changes at doses above 0.9 mg/kg. No evidence of vascular wall pathology or infection was observed in any animal. CONCLUSION: The greatest amount of DETA/NO safely delivered from EVAc copolymer to the subarachnoid space of the cynomolgus monkey is approximately 1.0 mg/kg. These findings show that continuous intracisternal delivery of DETA/NO is a safe and potentially effective strategy for prophylactic treatment of delayed cerebral vasospasm.

Animals↗
PubMed2006

Systemic administration of simvastatin after the onset of experimental subarachnoid hemorrhage attenuates cerebral vasospasm.

OBJECTIVE: Experimental evidence suggests that intercellular adhesion molecule-1 mediated leukocyte extravasation contributes to the pathogenesis of cerebral vasospasm. Simvastatin, an HMG-CoA reductase inhibitor, decreases intercellular adhesion molecule-1 expression and competitively inhibits leukocyte intercellular adhesion molecule-1 binding. We hypothesized that administration of simvastatin after the onset of subarachnoid hemorrhage (SAH) would attenuate perivascular granulocyte migration and ameliorate cerebral vasospasm in a rabbit model of SAH. METHODS: New Zealand white rabbits (n = 15) underwent injection of autologous blood into the cisterna magna or sham surgery followed by subcutaneous injection of simvastatin (40 mg/kg) or vehicle 30 minutes, 24 hours, and 48 hours after SAH or sham surgery. Seventy-two hours later, basilar artery lumen diameter was measured by in situ perfusion/fixation and image analysis. CD-18 monoclonal antibody stained perivascular granulocytes and macrophages were counted under light microscopy. RESULTS: In vehicle treated rabbits, mean +/- standard deviation basilar artery diameter was reduced 3 days after SAH (n = 5) versus sham (n = 5) rabbits (0.49 +/- 0.08 mm versus 0.75 +/- 0.03 mm, P < 0.01). After SAH, mean +/- standard deviation basilar artery diameter was greater in simvastatin (n = 5) treated rabbits versus vehicle (n = 5) (0.63 +/- 0.04 mm versus 0.49 +/- 0.08 mm, P < 0.01). In vehicle treated rabbits, SAH resulted in an increase in the mean +/- standard deviation perivascular CD18 cell count (sham-vehicle, 2.8 +/- 2; SAH-vehicle 90 +/- 27; P < 0.01). Subcutaneous administration of simvastatin attenuated this increase in perivascular CD18-positive cells after SAH (SAH statin, 41.6 +/- 13; SAH vehicle, 90 +/- 27; P < 0.001). CONCLUSION: Subcutaneous administration of simvastatin after the onset of SAH attenuates perivascular granulocyte migration and ameliorates basilar artery vasospasm after experimental SAH in rabbits. 5-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, such as simvastatin, may potentially serve as agents in the prevention of cerebral vasospasm after SAH.

Animals↗
PubMed2006

Hyperglycemia independently increases the risk of perioperative stroke, myocardial infarction, and death after carotid endarterectomy.

OBJECTIVE: Clinical and experimental evidence suggests that hyperglycemia lowers the neuronal ischemic threshold, potentiates stroke volume in focal ischemia, and is associated with morbidity and mortality in the surgical critical care setting. It remains unknown whether hyperglycemia during carotid endarterectomy (CEA) predisposes patients to perioperative stroke and operative related morbidity and mortality. METHODS: The clinical and radiological records of all patients undergoing CEA and operative day glucose measurement from 1994 to 2004 at an academic institution were reviewed and 30-day outcomes were assessed. The independent association of operative day glucose before CEA and perioperative morbidity and mortality were assessed via multivariate logistic regression analysis. RESULTS: One thousand two hundred and one patients with a mean age of 72 +/- 10 years (748 men, 453 women) underwent CEA (676 asymptomatic, 525 symptomatic). Overall, stroke occurred in 46 (3.8%) patients, transient ischemic attack occurred in 19 (1.6%), myocardial infarction occurred in 19 (1.6%), and death occurred in 17 (1.4%). Increasing operative day glucose was independently associated with perioperative stroke or transient ischemic attack (Odds ratio [OR], 1.005; 95% confidence interval [CI], 1.00-1.01; P = 0.03), myocardial infarction (OR, 1.01; 95% CI, 1.004-1.016; P = 0.017), and death (OR, 1.007; 95% CI, 1.00-1.015; P = 0.04). Patients with operative day glucose greater than 200 mg/dl were 2.8-fold, 4.3-fold, and 3.3-fold more likely to experience perioperative stroke or transient ischemic attack (OR, 2.78; 95% CI, 1.37-5.67; P = 0.005), myocardial infarction (OR, 4.29; 95% CI, 1.28-14.4; P = 0.018), or death (OR, 3.29; 95% CI, 1.07-10.1; P = 0.037), respectively. Median and interquartile range length of hospitalization was greater for patients with operative day glucose greater than 200 mg/dl (4 d [interquartile range, 2-15 d] versus 3 d [interquartile range, 2-7 d]; P < 0.05). CONCLUSION: Independent of previous cardiac disease, diabetes, or other comorbidities, hyperglycemia at the time of CEA was associated with an increased risk of perioperative stroke or transient ischemic attack, myocardial infarction, and death. Strict glucose control should be attempted before surgery to minimize the risk of morbidity and mortality after CEA.

Aged↗
PubMed2006

Orthogonal interlocking tandem clipping technique for the reconstruction of complex middle cerebral artery aneurysms.

OBJECTIVE: Complex aneurysms arising at the middle cerebral artery (MCA) bifurcation frequently present a microsurgical challenge to effectively obliterate while maintaining patency of the distal MCA branches. These aneurysms are often multilobed, with their long axis aligned with the long axis of the M1 trunk, placing the dome of the aneurysm in the surgeons' line of sight, preventing an unobstructed view of the entire bifurcation and proximal M1 segment. MCA aneurysms often have a broad neck, splaying the bifurcation. An orthogonal interlocking tandem clipping technique, maximizing the use of fenestrated aneurysm clips, is presented as a means to completely obliterate the aneurysm and simultaneously "reconstruct" the MCA bifurcation. CLINICAL PRESENTATIONS AND INTERVENTION: Fifteen complex MCA aneurysms were treated using an interlocking tandem clipping technique. In its simplest application, the blades of the initial aneurysm clip are incorporated into the fenestration of the second clip. Obliteration of the residual aneurysm is achieved with the blades of the second, fenestrated clip. RESULTS: Satisfactory aneurysm obliteration and reconstruction of the MCA bifurcation was achieved in all cases using this technique, with excellent neurological outcomes. CONCLUSION: Morphologically complex multilobed MCA aneurysms can be effectively clipped with "reconstruction" of the normal vascular anatomy using a tandem interlocking clipping technique. A fenestrated clip is used to incorporate the blades of the initial clip, while obliterating the remainder of the aneurysm.

Adult↗
PubMed2006

Intracranial aneurysm following radiation therapy during childhood for a brain tumor. Case report and review of the literature.

Ionizing radiation therapy is associated with pathological vascular changes in intracranial vessels, most commonly in the form of vessel thrombosis and occlusion. The development of an intracranial aneurysm following such therapy, however, is far less common. In this report the authors describe a 24-year-old man in whom a distal middle cerebral artery aneurysm developed 15 years after radiotherapy, which was given as adjuvant treatment following resection of a medulloblastoma. The patient underwent a craniotomy for microsurgical trapping of the aneurysm and was discharged without any neurological deficit. This case serves to remind clinicians of the possibility, albeit rare, that intracranial aneurysms may form following cranial radiotherapy.

Adult↗
PubMed2005

Orbitozygomatic approach to basilar apex aneurysms.

Basilar apex region aneurysms are among the most complex cerebral aneurysms. They are not, however, among the most common aneurysms, and increased use of endovascular treatment has further decreased the number of patients with these lesions who undergo surgery. Nonetheless, not all basilar apex aneurysms are amenable to coil embolization, and neurosurgeons must be prepared to treat patients with basilar apex aneurysms surgically. We prefer an orbitozygomatic craniotomy and transsylvian approach. Meticulous exercise of the basic tenets of aneurysm surgery (proximal vascular control, sharp dissection, and preservation of perforating vessels) is crucial to optimal patient outcomes.

Craniotomy↗
PubMed2005

Contralateral approaches to multiple cerebral aneurysms.

Not infrequently, patients with bilateral cerebral aneurysms are encountered. In such patients, the ability to treat bilateral aneurysms through a unilateral approach spares the patient the risk and inconvenience associated with a separate craniotomy. The contralateral approach for aneurysm repair is technically feasible and safe in appropriately selected patients. Herein, we review our technique for maximizing contralateral exposure and clipping contralateral aneurysms through the four anatomic triangles that serve as corridors in this approach.

Humans↗
PubMed2005

Local delivery of ibuprofen via controlled-release polymers prevents angiographic vasospasm in a monkey model of subarachnoid hemorrhage.

OBJECTIVE: Adhesion and migration of leukocytes into the periadventitial space play a role in the pathophysiology of vasospasm after subarachnoid hemorrhage (SAH). Intercellular adhesion molecule-1 is a determinant cell adhesion molecule involved in this process. Ibuprofen has been shown to inhibit intercellular adhesion molecule-1 upregulation and prevent vasospasm in animal models of SAH. In this study, we report the toxicity and efficacy of locally delivered ibuprofen incorporated into controlled-release polymers to prevent vasospasm in a monkey model of SAH. METHODS: Ibuprofen was incorporated into ethylene-vinyl acetate (EVAc) polymers at 45% loading (wt:wt). For the toxicity study, cynomolgus monkeys (n = 5) underwent surgical implantation of either blank/EVAc polymers (n = 3) or 45% ibuprofen/EVAc polymers (n = 2) in the subarachnoid space, were followed up for 13 weeks, and were killed for histopathological analysis. For the efficacy study, cynomolgus monkeys (n = 14) underwent cerebral angiography 7 days before and 7 days after surgery and SAH and were randomized to receive either a 45% ibuprofen/EVAc polymer (n = 7; mean dose of ibuprofen, 6 mg/kg) or blank EVAc polymers (n = 7) in the subarachnoid space. Angiographic vasospasm was determined by digital image analysis. Student's t test was used for analysis. RESULTS: Animals implanted with ibuprofen polymers showed no signs of local or systemic toxicity. Animals treated with ibuprofen polymers had 91 +/- 9% lumen patency of the middle cerebral artery, compared with 53 +/- 11% of animals treated with blank/EVAc polymers (P < 0.001). CONCLUSION: Ibuprofen polymers are safe and prevent angiographic vasospasm after SAH in the monkey model. These findings support the role of cell adhesion molecules and inflammation in the pathophysiology of vasospasm.

Animals↗
PubMed2005

Supratentorial arteriovenous malformations.

Arteriovenous malformations are a heterogeneous group of intra-axial central nervous system vascular lesions consisting of tangles of abnormal arteriovenous connections without intervening capillary beds. The heterogeneity of arteriovenous malformations is described by the Spetzler-Martin grading scale, a scale that also forms the basis for clinical decision making. The microsurgical treatment of appropriately selected supratentorial arteriovenous malformations is based on the tenets of circumferential isolation and transection of arterial feeders, preservation of vessels en passant and surrounding functional neural tissue, and skeletonization and transection of venous drainage.

Brain↗
PubMed2005

Controlled release of a nitric oxide donor for the prevention of delayed cerebral vasospasm following experimental subarachnoid hemorrhage in nonhuman primates.

OBJECT: Results of prior studies in rats and rabbits show that the alteration of vasomotor tone in vasospasm following periadventitial blood exposure may be reversed, at least in part, by the administration of compounds releasing nitric oxide (NO). The authors have now generalized this finding to nonhuman primates. METHODS: Ten cynomolgus monkeys underwent cerebral angiography before and 7 days following the induction of subarachnoid hemorrhage (SAH) by the placement of 2 to 3 ml clotted autologous blood around the supraclinoid carotid, proximal anterior cerebral, and proximal middle cerebral arteries. An ethylene vinyl acetate copolymer, either blank (five animals) or containing 20% w/w (Z)-1-[2-(2-aminoethyl)-N-(2-aminoethyl)amino]diazen-1-ium-1,2-diolate (DETA/NO, 4.3 mg/kg; five animals) was placed adjacent to the vessels at the time of surgery. Animals were killed on Day 7 post-SAH following repeated cerebral angiography. The mean percentage of control vascular areal fraction was calculated from angiograms. Cerebral vessels were sectioned and the mean percentage of lumen patency was calculated. One animal that had received the DETA/NO polymer died prior to repeated angiography. In the remaining animals, DETA/NO caused a significant decrease in vasospasm compared with controls, according to both angiographic (84.8 +/- 8.6 compared with 56.6 +/- 5.2%, respectively, p < 0.05) and histological studies (internal carotid artery 99.3 +/- 1.8 compared with 60.1 +/- 4.4%, respectively, p < 0.001; middle cerebral artery 98.4 +/- 3 compared with 56.1 +/- 3.7%, respectively, p < 0.001; and anterior cerebral artery 89.2 +/- 8.5 compared with 55.8 +/- 6.3%, respectively, p < 0.05). CONCLUSIONS: The controlled release of DETA/NO is effective in preventing delayed cerebral vasospasm in an SAH model in nonhuman primates. The death of one animal in the treatment group indicates that the present dosage is at the threshold between therapeutic efficacy and toxicity.

Animals↗
PubMed2004

Segmental agenesis of the internal carotid artery distal to the posterior communicating artery leading to the definition of a new embryologic segment.

We report a case of segmental agenesis of the right internal carotid artery (ICA) in a 53-year-old woman, associated with a saccular aneurysm of the left anterior cerebral artery (A1 segment) presenting with a right hemispheric transient ischemic attack. The agenetic segment was located distal to the origin of the posterior communicating artery (PComA), as documented both angiographically and by direct surgical inspection. This observation suggests the existence of a previously unrecognized embryologic segment of the ICA, located between the PComA origin and the terminal bifurcation of the ICA into the anterior and middle cerebral arteries.

Angiography, Digital Subtraction↗
PubMed2003

High-dose ibuprofen for reduction of striatal infarcts during middle cerebral artery occlusion in rats.

OBJECT: Ibuprofen is an antiinflammatory drug that disrupts leukocyte-endothelial cell interactions by limiting expression of endothelial adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1), also known as CD54. The authors hypothesized that ibuprofen could reduce the size of the infarct associated with transient focal ischemia by inhibition of ICAM-1 expression, and they evaluated its effects in rats treated with middle cerebral artery (MCA) occlusion. Ibuprofen treatment was compared with mild systemic hypothermia, which is known to be neuroprotective and is commonly used during neurosurgical procedures. METHODS: The maximum ibuprofen dose (240 mg/kg/day) that could be tolerated with no systemic toxicity was established in the initial experiments. In the efficacy experiment, rats were pretreated with vehicle, ibuprofen, or hypothermia (33 degrees C) prior to 2 hours of MCA occlusion; then their brains were harvested at 24 hours of reperfusion for histological studies. End-ischemic cerebral blood flow (CBF) was evaluated using [14C]iodoantipyrine autoradiography in additional cohorts. Expression of ICAM-1 within ischemic compared with nonischemic caudate nucleus and putamen (striatum) or cortex was evaluated using immunohistochemical studies. Compared with vehicle treatment, ibuprofen produced a 46.2% reduction (p = 0.01) in striatal infarcts, which was comparable to hypothermia (48.7% reduction, p = 0.02). Ibuprofen did not alter end-ischemic CBF in any region studied, and the ibuprofen treatment group had the lowest proportion of animals with marked ICAM-1 staining. CONCLUSIONS: Ibuprofen given in maximum tolerated doses reduces the striatal infarct size after focal cerebral ischemia. The neuroprotective mechanism does not work through preservation of intraischemic CBF and is consistent with inhibition of ICAM-1 expression; however, at the doses used in this study, other effects of ibuprofen on platelet and endothelial function are possible.

Animals↗
PubMed2003

Prevention of cerebral vasospasm by a humanized anti-CD11/CD18 monoclonal antibody administered after experimental subarachnoid hemorrhage in nonhuman primates.

OBJECT: Leukocyte-endothelial cell interactions occurring in the first hours after subarachnoid hemorrhage (SAH) initiate changes in the endothelium and vessel wall that lead to an influx of leukocytes and the development of chronic vasospasm days later. Upregulation of intercellular adhesion molecule-1 (ICAM-1), also called CD54, appears to be a crucial step in this process. There is increasing experimental evidence that blocking the interaction between ICAM-1, which is expressed on endothelium, and integrins such as lymphocyte function-associated antigen-1 (CD11a/CD18) and macrophage antigen-1 (complement receptor 3, CD11b/CD18), which are expressed on the surface of leukocytes,prevents not only inflammation of vessel walls but also chronic vasospasm. The authors extend their previous work with monoclonal antibody (mAb) blockade of leukocyte migration to a nonhuman primate model of chronic, posthemorrhagic cerebral vasospasm. METHODS: Before surgery was performed, six young adult male cynomolgus monkeys underwent baseline selective biplane common carotid and vertebrobasilar artery cerebral angiography via a transfemoral route. On Day 0, a right frontosphenotemporal craniectomy was performed with arachnoid microdissection and placement of 2 to 3 ml of clotted autologous blood in the ipsilateral basal cisterns. The animals were given daily intravenous infusions of 2 mg/kg of either a humanized anti-CD11/CD18 or a placebo mAb beginning 30 to 60 minutes postoperatively. The monkeys were killed on Day 7 after a repeated selective cerebral angiogram was obtained. The area of contrast-containing vessels observed in each hemisphere on anteroposterior angiographic views was calculated for the angiograms obtained on Day 7 and expressed as a percentage of the area on baseline angiograms (percent control areal fraction). Review of flow cytometry and enzyme immunoassay data confirmed the presence of the anti-CD11/CD18 antibody in the serum and bound to leukocytes in the peripheral blood of treated animals. Comparisons of the groups revealed 53 +/- 4.8% control vascular areal fraction in the placebo group (two animals) and 95.8 +/- 9.4% in the anti-CD11/CD18-treated group (three animals), a statistically significant difference (p = 0.043, t-test). CONCLUSIONS: These results show that blockade of leukocyte migration into the subarachnoid space by an anti-CD11/CD18 mAb is effective in preventing experimental cerebral vasospasm in nonhuman primates, despite the unaltered presence of hemoglobin in the subarachnoid space. These experimental data support the hypothesis that inflammation plays a role in cerebral vasospasm after SAH.

Animals↗
PubMed2003

Developmental venous anomalies and sinus pericranii in the blue rubber-bleb nevus syndrome. Case report.

Blue rubber-bleb nevus syndrome (BRBNS) is a developmental disorder that originally was identified by the presence of distinctive cutaneous and gastrointestinal hemangiomas. More recently it has been recognized that the number of affected organs is larger and that BRBNS includes central nervous system vascular malformations. A 52-year-old woman in whom intracranial vascular malformations had been diagnosed earlier presented for evaluation. At birth, several blue nevi had been noted on her tongue, lips, and neck. Cerebral angiography demonstrated an extensive network of developmental venous anomalies and a left anterior sinus pericranii. The literature on BRBNS and developmental venous anomalies is reviewed.

Cerebral Angiography↗
PubMed2003

A surgical technique for safely placing a drug delivery catheter into the pons of primates: preliminary results of carboplatin infusion.

OBJECTIVE: We sought to develop a neurosurgical procedure to access the pons with a drug delivery device for chronic therapy and collect preliminary data on the toxicity of direct infusions of carboplatin in primates. METHODS: We made midline incisions on five cynomolgus monkeys, identified the inion, made a burr hole 2.5 cm below the inion, and inserted a catheter through the cerebellum into the roof of the pons. Pumps that infused saline for 90 days or carboplatin solutions for 30 to 35 days at 10 microl/d were placed subcutaneously in the low cervical/high thoracic region. Monkeys were assessed by computed tomography and magnetic resonance imaging, laboratory studies, daily neurological observation, postmortem examinations, and histopathology. RESULTS: Monkeys infused with saline and 82 microg of carboplatin remained neurologically intact throughout the infusion periods. Serial imaging showed that the catheter tip was in the pons and revealed no evidence of hemorrhage, edema, or migration. Two monkeys infused with up to 850 microg of carboplatin showed hyperintense magnetic resonance imaging signals at Days 15 and 18 and neurological deficits at approximately Week 3. Platinum levels greater than 10 ng/mg tissue were detected over a distance of 1 cm in tissue slices. Histopathology demonstrated significant tissue necrosis around the tip of the catheter. CONCLUSION: The pons of monkeys is safely accessed with a catheter for drug delivery by using a posterior midline approach. Clinical observations, radiographic imaging, and laboratory tests of animals infused with saline for 3 months or 0.26 mg/ml of carboplatin for 1 month were unremarkable. Neurotoxicity was seen with dose levels of 2.6 mg/ml of drug for 1 month. This procedure offers opportunities for examining the toxicity of brainstem antitumor therapy in primates.

Animals↗
PubMed2003

Discovering the novel surgical approach.

Discovering the novel surgical approach requires surgeons to look beyond the dogma of current practices. By applying simple principles and concepts, such as the two-point method, working depth, working area, and angle of attack, novel approaches can evolve from existing approaches to improve exposure and decrease patient morbidity. The EOZ and ELSI are two examples in which these principles have been applied to generate novel surgical approaches by modifying existing ones. Compared to the previously used approaches, both of these novel approaches afford superior access to their respective regions of the brain stem with decreased rates of morbidity.

Brain Diseases↗