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Biomedical subjects

M Stoodley

Publications and source records attributed to M Stoodley.

12 recordsLinked to original sources
PubMed2007

In vitro and in vivo tissue repair with laser-activated chitosan adhesive.

BACKGROUND AND OBJECTIVES: Sutures are currently the gold standard for wound closure but they are still unable to seal tissue and may induce scarring or inflammation. Biocompatible glues, based on polysaccharides such as chitosan, are a possible alternative to conventional wound closure. In this study, the adhesion of laser-activated chitosan films is investigated in vitro and in vivo. In particular we examine the effect of varying the laser power, as well as adding a natural cross-linker (genipin) to the adhesive composition. STUDY DESIGN/MATERIALS AND METHODS: Flexible and insoluble strips of chitosan films (surface area approximately 34 mm(2), thickness approximately 20 microm) were bonded to sheep intestine using several laser powers (0, 80, 120, and 160 mW) at 808-nm wavelength. The strength of repaired tissue was tested by a calibrated tensiometer to select the best power. A natural cross-linker (genipin) was also added to the film and the tissue repair strength compared with the strength of plain films. The adhesive was also bonded in vivo to the sciatic nerve of rats and the thermal damage induced by the laser assessed 4 days post-operatively. RESULTS: Chitosan adhesives successfully repaired intestine tissue, attaining a maximum repair strength of 14.7+/-4.3 kPa (n = 30) at the laser power of 120 mW. The chitosan-genipin films achieved lower repair strength (9.1+/-2.9 kPa). The laser caused partial demyelination of axons at the site of operation, but the myelinated axons retained a normal morphology proximally and distally. CONCLUSIONS: The chitosan adhesive effectively bonded to tissue causing only localized thermal damage in vivo, when the appropriate laser parameters were selected.

Animals↗
PubMed2004

Angiographic, hemodynamic and histological characterization of an arteriovenous fistula in rats.

BACKGROUND: Our understanding of the pathogenesis of arteriovenous malformations (AVMs) and arteriovenous fistulas (AVFs) has been limited by the lack of adequate animal models. In this study we evaluate the time course of angiographic, hemodynamic and histopathological changes in an arteriovenous fistula in rats as a potential model. METHODS: An arteriovenous fistula was created by a side-to-end anastomosis of the common carotid artery (CCA) to the external jugular vein (EJV). The animals underwent angiography of the fistula and were sacrificed 1, 7, 21, 42 or 90 days later. Flow and pressure measurements were performed in the CCA and ipsi- and contralateral EJV and detailed histological examination of whole mount sections of the fistula and cranium were done on fixed sections. Immunohistochemistry for CD31, smooth muscle alpha-actin and Ki-67 were performed. FINDINGS: Hemodynamic changes occur immediately after fistula formation creating a stable high flow, low resistant state. This induces a gradual increase in the inner diameter of the EJV and transverse sinus followed by a decrease in size of the transverse sinus. This decrease is associated with increased expression of alpha-actin in the wall of the sinus. The fistula becomes angiographically and histologically stable after 21 days. CONCLUSION: This model describes the time course of hemodynamic and histopathological changes after occur after AVF formation. Stabilization after 21 days makes it an attractive model for mechanistic and therapeutic studies of AVFs.

Animals↗
PubMed2000

Intraoperative variables and early outcome after aneurysm surgery.

BACKGROUND: The purpose of this study was to investigate the effects of blood pressure, temperature, and anesthetic agents on outcome in patients undergoing craniotomy for cerebral aneurysms. METHODS: All ruptured and unruptured intracranial aneurysms operated on from 1992 to 1998 were reviewed retrospectively. The data included 297 aneurysms (190 ruptured and 107 unruptured). Data were collected on variables known to influence outcome after aneurysmal subarachnoid hemorrhage as well as on intraoperative factors that might influence outcome (intraoperative blood pressure, temperature, temporary clipping, anesthetic agents). Outcome was assessed at discharge using the Glasgow Outcome Scale. RESULTS: In univariate analysis of patients with ruptured aneurysms, younger age, better clinical grade, lower Fisher grade, lower intraoperative blood pressure (maximum systolic and mean blood pressure), smaller decrease in intraoperative compared to preoperative systolic blood pressure, shorter duration of surgery, and use of propofol, pancuronium, or N(2)O were associated with significantly better outcome. In patients with unruptured aneurysms, increased intraoperative minimum diastolic and mean blood pressure, a decrease in the difference between multiple measures of preoperative and intraoperative blood pressure, and a shorter duration of surgery were associated with significantly better outcome. Intraoperative temperature did not affect outcome in either group. In multivariate analysis of patients with ruptured aneurysms, younger age, better clinical grade, lower maximum systolic intraoperative blood pressure, shorter duration of surgery, and use of propofol were independently associated with better outcome. CONCLUSIONS: Multivariate analysis of intraoperative factors affecting outcome in patients undergoing craniotomy for ruptured aneurysms shows that decreased intraoperative blood pressure and use of propofol are associated with improved outcome. Univariate analysis suggests that decreasing the magnitude of drop in blood pressure intraoperatively from preoperative values in patients with ruptured or unruptured aneurysms is associated with better outcome. Intraoperative hypothermia did not affect outcome.

Anesthetics↗
PubMed2000

Effect of adenovirus-mediated nitric oxide synthase gene transfer on vasospasm after experimental subarachnoid hemorrhage.

OBJECTIVE: Evidence indicates that vasospasm after subarachnoid hemorrhage (SAH) is caused in part by a decrease in the vasodilator nitric oxide (NO), which is produced mainly in endothelial cells. This study tested whether intracisternal injection of adenovirus-expressing endothelial NO synthase (eNOS) would decrease vasospasm in dogs. METHODS: In 12 dogs, baseline cerebral angiography was performed, and then SAH was produced by two injections of blood into the cisterna magna. The dogs were randomized (n = 6/group) to intracisternal injection of adenovirus-expressing lacZ (Ad327beta-Gal) or eNOS (AdCD8-NOS), administered immediately after the first blood injection. Angiography was repeated on Day 7, and then L-arginine (50 mg) was administered intracisternally, and angiography was repeated. Cerebrospinal fluid aspirated from the cisterna magna on Days 2 and 7 was analyzed for levels of NO metabolites. The dogs were killed, and their basilar arteries were removed and studied pharmacologically. Four control dogs underwent angiography on Day 0, followed by virus injection (n = 2/group). Angiography was repeated on Day 7, and the control dogs were killed. Transgene expression was detected in tissue removed on Day 7 by histochemical staining for lacZ, by polymerase chain reaction for messenger ribonucleic acid for eNOS, and by measurement of NO metabolites in cerebrospinal fluid. RESULTS: Angiography showed significant vasospasm in each group (Ad327beta-Gal, -54 +/- 7% reduction in basilar artery diameter; AdCD8-NOS, -53 +/- 7%), with no significant difference between groups. Injection of L-arginine caused an insignificant increase in arterial diameter in each group. In dogs without SAH, Ad327beta-Gal caused a reduction in basilar artery diameter (-13 +/- 10%, P = 0.42; paired t test), whereas injection of AdCD8-NOS caused an increase in diameter (14 +/- 16%, P = 0.77; paired t test). Histological examination and beta-galactosidase staining of dogs given injections of Ad327beta-Gal showed staining in inflammatory cells in the subarachnoid space, in the adventitia of the cerebral vessels, and in the liver and lungs. Messenger ribonucleic acid for eNOS was detected in the leptomeninges of dogs given injections of AdCD8-NOS. Under isometric tension, basilar arteries from each group demonstrated similar relaxation to L-arginine, but arteries exposed to eNOS demonstrated significantly greater relaxation to L-arginine plus tetrahydrobiopterin than arteries exposed to lacZ. Cerebrospinal fluid levels of NO and its metabolites were significantly higher in dogs treated with AdCD8-NOS than those treated with Ad327beta-Gal 2 days after SAH. CONCLUSION: These results demonstrate that adenovirus vectors can be used to transfer genes to cells in the subarachnoid space of dogs. Enough NO can be produced in the absence of SAH to dilate the basilar artery. After SAH, however, NO plus a cofactor can dilate arteries in vitro, but not enough NO is generated in the subarachnoid space to prevent vasospasm, perhaps owing to the scavenging of NO by hemoglobin.

Adenoviridae↗
PubMed2000

Adenoviral gene transfer of nitric oxide synthase increases cerebral blood flow in rats.

OBJECTIVE: Depletion of nitric oxide may play a role in the development of vasospasm after aneurysmal subarachnoid hemorrhage. Replenishment of nitric oxide might be a useful treatment for vasospasm. Using rats, we performed intracisternal injections of replication-defective adenovirus containing the endothelial nitric oxide synthase (eNOS) gene and determined the localization of and effect on cerebral blood flow of transgene expression. METHODS: Rats underwent baseline measurement of cortical cerebral blood flow using laser Doppler flowmetry. Replication-defective adenovirus containing the Escherichia coli LacZ gene (Ad327beta-Gal, n = 2/time point) or the bovine eNOS gene (AdCD8-NOS, n = 4/time point) or physiological saline solution was injected into the cisterna magna. Cerebral blood flow was measured 1, 2, 4, 7, or 14 days later, and the animals were killed. Expression of beta-galactosidase activity from the LacZ gene was examined by histochemical staining and that of eNOS was examined by polymerase chain reaction assays of messenger ribonucleic acid. Brains were histopathologically examined for inflammation. RESULTS: Beta-galactosidase activity was observed throughout the leptomeninges and in some cells in the adventitia of small subarachnoid blood vessels in the Ad327beta-Gal-injected rats. Messenger ribonucleic acid for eNOS was detected in the leptomeninges and brainstem 1 and 2 days after injection of AdCD8-NOS. Rats injected with Ad327beta-Gal or physiological saline solution exhibited decreased cerebral blood flow beginning 2 days after virus injection and lasting up to 14 days after injection. Rats injected with AdCD8-NOS developed significant transient increases in cerebral blood flow 2 days after virus injection, followed by slight decreases in blood flow. There was inflammation in the subarachnoid space of all animals; the inflammation was qualitatively worse in animals injected with Ad327beta-Gal, compared with rats injected with AdCD8-NOS or saline solution. CONCLUSION: Intracisternal injection of replication-defective adenovirus containing the eNOS gene can transiently increase cerebral blood flow.

Animals↗
PubMed2000

Subarachnoid hemorrhage as a cause of an adaptive response in cerebral arteries.

OBJECT: It is not known whether the factors responsible for vasospasm after subarachnoid hemorrhage (SAH) cause the cerebral arteries to be narrowed independent of the subarachnoid blood clot or whether the continued presence of clot is required for the entire time of vasospasm. The authors undertook the present study to investigate this issue. METHODS: To distinguish between these possibilities, bilateral SAH was induced in monkeys. The diameters of the monkeys' cerebral arteries were measured on angiograms obtained on Days 0 (the day of SAH), 1, 3, 5, 7, and 9. The subarachnoid blood clot was removed surgically on Day 1, 3, or 5 or, in control animals, was not removed until the animals were killed on Day 7 or 9. The concentrations of hemoglobins and adenosine triphosphate (ATP), substances believed to cause vasospasm, were measured in the removed clots and the contractile activity of the clots was measured in monkey basilar arteries in vitro. If the clot was removed 1 or 3 days after placement, vasospasm was significantly diminished 4 days after clot removal. Clot removal on Day 5 had no marked effect on vasospasm. There was a significant decrease over time in hemoglobin and ATP concentrations and in the contractile activity of the clots, although substantial hemoglobin and contractile activity was still present on Day 7. CONCLUSIONS: The authors infer from these results that vasospasm requires the presence of subarachnoid blood for at least 3 days, whereas by Day 5 vasospasm is less dependent on subarachnoid blood clot. Because the clot still contains substantial amounts of hemoglobin and contractile activity after 5 days, there may be an adaptive response in the cerebral arteries that allows them to relax in the presence of the stimulus that earlier caused contraction.

Adaptation, Physiological↗
PubMed2000

Contents of chronic subdural hematoma.

Analysis of chronic subdural hematoma membranes and contents has revealed a complex process of blood breakdown forming a milieu that stimulates neovascularization and repeated hemorrhage.

Blood Proteins↗
PubMed1999

Etiology of cerebral vasospasm.

Cerebral vasospasm is a gradual onset and prolonged constriction of the cerebral arteries in the subarachnoid space after subarachnoid hemorrhage. The principal cause is the surrounding blood clot. The significance of vasospasm is that flow through the constricted arteries may be reduced sufficiently to cause cerebral infarction. Subarachnoid blood clot is sufficient to cause vasospasm; it does not require additional arterial injury, intracranial hypertension or brain infarction, although these elements are often coexistent. The blood released at the time of aneurysmal rupture into the alien subarachnoid environment is an extraordinarily complex mix of cellular and extracellular elements that evolves as clotting occurs; cells disintegrate; local inflammation, phagocytosis and repair take place; severe constriction alters the metabolism and structure of the arterial wall as well as the balance of vasoconstrictor and dilator substances produced by its endothelium, neurogenic network and perhaps smooth muscle cells.

Brain↗
PubMed1999

Gene therapy for cerebrovascular disease.

OBJECTIVE: To review the principles of and the experimental and clinical results of gene therapy for cerebrovascular disease. METHODS: Literature review. RESULTS: Vectors for gene transfer into the brain or into the cerebral vasculature include naked plasmid deoxyribonucleic acid, cationic liposomes, and viruses such as adenovirus, retrovirus, adeno-associated virus, and herpes simplex virus. Experiments using these vectors showed that intra- or perivascular application to systemic arteries can lead to transfection and expression of a foreign transgene in the adventitia and the endothelium. Intrathecal administration can lead to transfection and foreign transgene expression in leptomeningeal cells as well as in fibroblasts of blood vessel adventitia. Biological effects demonstrated thus far include increased nitric oxide production by transfection of cerebral arterial adventitia with adenovirus expressing nitric oxide synthase. Adenoviruses carrying foreign genes have been used to decrease neuronal damage in cerebral ischemia and to decrease blood pressure in spontaneously hypertensive rats. Vectors and therapeutic applications for gene therapy are evolving rapidly. CONCLUSION: Gene therapy for cerebrovascular disease is likely to have clinical application in the near future and will have a major impact on neurosurgery. Neurosurgeons will need to be aware of the literature in this area.

Animals↗
PubMed1998

Pathophysiology of cerebral ischemia.

The purpose of this manuscript is to briefly review the pathophysiology of cerebral ischemia. Ischemic thresholds are well-defined in lower animals. The concept of the ischemic penumbra may include regions of brain around deeper regions of ischemia but has also been defined in terms of brain salvageable by reperfusion or by pharmacological therapies. The principal pathophysiological processes in cerebral ischemia are energy failure, loss of cell ion homeostasis, acidosis, increased intracellular calcium, excitotoxicity, and free radical-mediated toxicity. The underlying biochemical processes are similar regardless of the amount of brain that is made ischemic or the duration of ischemia. The relative contributions of each process are believed to vary significantly especially in relation to the level of cerebral blood flow. Neurons may die by necrosis or apoptosis. In the core of an infarct where blood flow is very low, the predominant process is energy failure and rapid necrotic cell death. Reperfusion of ischemic tissue produces an influx of inflammatory cells and of oxygen that can cause increases in oxygen-derived free radicals. Free radicals are also important in prolonged ischemia. There is interest in changes in gene expression after ischemia. Induction of heat shock proteins suggests that gene expression changes may protect neurons from death. Changes in gene expression also may initiate apoptosis or other detrimental processes. Although advances have been made, there are still no proven pharmacological therapies to rescue ischemic human neurons. Such therapies do appear to be on the horizon.

Animals↗
PubMed1987

Objective and useful mobility assessment of patients with arthropathy of the hip and knee.

Walking ability was objectively assessed by measurements of endurance, oxygen consumption, and pulse rate response. Twenty-four control subjects and 38 patients with arthropathy of the hip or knee were asked to walk on a treadmill, initially at 1 km/hour, for four minutes. The speed was increased by 1 km/hour every four minutes, until the subjects has walked for four minutes at 7 km/hour, or until they could not continue. Oxygen consumption, heart rate, cadence, and step length were measured. The controls could all walk for 1400 m, reaching a walking speed of 6 km/hour, and showed a consistent relation between heart rate, oxygen consumption, and speed of walking. The majority of arthritic patients failed to reach either this distance or speed. They had a significantly increased metabolic cost, and there was a good correlation (r = 0.65 to 0.99) between the changes in pulse rate and oxygen consumption in each individual patient. The endurance, heart rate response, and oxygen consumption changes shown by patients proved to be reproducible characteristics in patients whose disease was static.

Adult↗