Search PubMed⌕ Search

Biomedical subjects

M Sean Grady

Publications and source records attributed to M Sean Grady.

29 records · Page 2Linked to original sources
PubMed2004

The effect of nimodipine on cerebral oxygenation in patients with poor-grade subarachnoid hemorrhage.

OBJECT: Nimodipine has been shown to improve neurological outcome after subarachnoid hemorrhage (SAH); the mechanism of this improvement, however, is uncertain. In addition, adverse systemic effects such as hypotension have been described. The authors investigated the effect of nimodipine on brain tissue PO2. METHODS: Patients in whom Hunt and Hess Grade IV or V SAH had occurred who underwent aneurysm occlusion and had stable blood pressure were prospectively evaluated using continuous brain tissue PO2 monitoring. Nimodipine (60 mg) was delivered through a nasogastric or Dobhoff tube every 4 hours. Data were obtained from 11 patients and measurements of brain tissue PO2, intracranial pressure (ICP), mean arterial blood pressure (MABP), and cerebral perfusion pressure (CPP) were recorded every 15 minutes. Nimodipine resulted in a significant reduction in brain tissue PO2 in seven (64%) of 11 patients. The baseline PO2 before nimodipine administration was 38.4+/-10.9 mm Hg. The baseline MABP and CPP were 90+/-20 and 84+/-19 mm Hg, respectively. The greatest reduction in brain tissue PO2 occurred 15 minutes after administration, when the mean pressure was 26.9+/-7.7 mm Hg (p < 0.05). The PO2 remained suppressed at 30 minutes (27.5+/-7.7 mm Hg [p < 0.05]) and at 60 minutes (29.7+/-11.1 mm Hg [p < 0.05]) after nimodipine administration but returned to baseline levels 2 hours later. In the seven patients in whom brain tissue PO2 decreased, other physiological variables such as arterial saturation, end-tidal CO2, heart rate, MABP, ICP, and CPP did not demonstrate any association with the nimodipine-induced reduction in PO2. In four patients PO2 remained stable and none of these patients had a significant increase in brain tissue PO2. CONCLUSIONS: Although nimodipine use is associated with improved outcome following SAH, in some patients it can temporarily reduce brain tissue PO2.

Aged↗
PubMed2004

Severe posttraumatic craniocervical instability in the very young patient. Report of three cases.

Children younger than 3 years of age represent a distinct subpopulation of patients at particular risk for high cervical and craniovertebral injuries. There are few descriptions of survivors of severe craniocervical trauma among the very young, and scarce data exist regarding management after initial emergency stabilization. The authors describe three children, age 1 to 32 months, who presented with craniocervical junction injuries. Variable neurological findings were observed at presentation (cranial nerve deficits, obtundation, and moderate-to-severe quadriparesis). All three were treated with prolonged immobilization and have recovered with minimal to no neurological deficit.

Child, Preschool↗
PubMed2003

Neuronal and glial cell number in the hippocampus after experimental traumatic brain injury: analysis by stereological estimation.

Fluid percussion (FP) brain injury causes spatial memory dysfunction in rats regardless of injury location (midline vs. lateral). Standard histological analysis of the injured brains shows hippocampal neuronal loss after lateral, but not midline FP injury. We have used the optical volume fractionator (OVF) stereological procedure to quantify neuronal loss and glial proliferation within specific subregions of the hippocampus after midline or lateral FP injury. The OVF method is a design-based cell counting procedure, which combines cellular numerical density estimates (from the optical disector) with volume estimates (generated by point counting and the fractionator stereology method) to produce an estimate of the absolute cell number. Fifteen adult male Sprague-Dawley rats were randomly divided into 3 groups (n = 5/group): midline injury, lateral injury and naive. A single fluid percussion pulse was delivered to anesthetized rats in the injured groups. At 14 days post-injury, strict morphological criteria enabled the estimation of neurons, astrocytes, oligodendrocytes, and microglia in defined hippocampal subregions. The results confirm that hippocampal neurons are selectively vulnerable to brain injury, particularly observed as a significant loss in the hilus following both types of injury and in area CA3 after lateral injury. In contrast, the number of astrocytes and oligodendrocytes remains unaffected by brain injury, regardless of subregion. However, the significant increase in microglia number (bilaterally after midline and ipsilateral following lateral injury) suggests that underlying cellular processes continue weeks following injury. The implications of the observed cell population changes are discussed in relation to the reported cognitive deficits associated with both lateral and midline FP brain injury.

Animals↗
PubMed2003

Intracranial hypotension after intraoperative lumbar cerebrospinal fluid drainage.

OBJECTIVE: Intraoperative lumbar cerebrospinal fluid drainage is frequently performed in a variety of neurosurgical procedures. A retrospective review is presented of the complications of lumbar cerebrospinal fluid drainage. METHODS: The records from 75 consecutive operations requiring intraoperative lumbar cerebrospinal drainage during a 1-year period at the Hospital of the University of Pennsylvania were reviewed to assess the types of complications attributable to spinal drainage and their rates of occurrence. The operations were categorized into 46 aneurysm clippings, 21 craniotomies for tumors, and 8 other cranial base procedures. RESULTS: Two patients developed transient postoperative neurological complications as a result of intracranial hypotension that resolved after epidural blood patching, with a reexploration craniotomy to drain an epidural collection performed in one patient. A third patient in the study developed a persistent deficit when intracranial hypotension led to intraoperative transtentorial herniation, which resulted in an unusual constellation of multiple brainstem infarcts that caused cranial neuropathy. CONCLUSION: Complications of intraoperative lumbar cerebrospinal fluid drainage resulting in transient (2 of 75 patients, 3%) or persistent (1 of 75 patients, 1%) neurological deficits caused by intracranial hypotension occur infrequently and may be related to preexisting conditions such as hydrocephalus.

Adult↗
PubMed2003

Comparison of anterior and posterior approaches in cervical spinal cord injuries.

This study reports the results of 52 patients with unstable cervical spine injuries and associated spinal cord injuries randomized to either anterior or posterior stabilization and fusion. All patients had achieved reduction and had unstable injuries that were thought to require surgical stabilization. Patients requiring a specific approach for either reduction or decompression were not included. Frankel grades and ASIA motor index scores were followed in each patient as well as fusion status, changes in alignment, and pain at final follow-up. Neurologic improvement was noted in each group with no significant differences. In the anterior group, 70% improved at least 1 Frankel grade and 57% improved 1 Frankel grade in the posterior group. There were two nonunions in the anterior group (90% fusion) and none in the posterior group (100% fusion), although this was not statistically different. Seven patients in each group complained of pain at the final follow-up. There were no significant differences in fusion rates, alignment, neurologic recovery, or long-term complaints of pain in patients treated with either anterior or posterior fusion and instrumentation.

Adult↗
PubMed2003

Structural and functional damage sustained by mitochondria after traumatic brain injury in the rat: evidence for differentially sensitive populations in the cortex and hippocampus.

The cellular and molecular pathways initiated by traumatic brain injury (TBI) may compromise the function and structural integrity of mitochondria, thereby contributing to cerebral metabolic dysfunction and cell death. The extent to which TBI affects regional mitochondrial populations with respect to structure, function, and swelling was assessed 3 hours and 24 hours after lateral fluid-percussion brain injury in the rat. Significantly less mitochondrial protein was isolated from the injured compared with uninjured parietotemporal cortex, whereas comparable yields were obtained from the hippocampus. After injury, cortical and hippocampal tissue ATP concentrations declined significantly to 60% and 40% of control, respectively, in the absence of respiratory deficits in isolated mitochondria. Mitochondria with ultrastructural morphologic damage comprised a significantly greater percent of the population isolated from injured than uninjured brain. As determined by photon correlation spectroscopy, the mean mitochondrial radius decreased significantly in injured cortical populations (361 +/- 40 nm at 24 hours) and increased significantly in injured hippocampal populations (442 +/- 36 at 3 hours) compared with uninjured populations (Ctx: 418 +/- 44; Hipp: 393 +/- 24). Calcium-induced deenergized swelling rates of isolated mitochondrial populations were significantly slower in injured compared with uninjured samples, suggesting that injury alters the kinetics of mitochondrial permeability transition (MPT) pore activation. Cyclosporin A (CsA)-insensitive swelling was reduced in the cortex, and CsA-sensitive and CsA-insensitive swelling both were reduced in the hippocampus, demonstrating that regulated MPT pores remain in mitochondria isolated from injured brain. A proposed mitochondrial population model synthesizes these data and suggests that cortical mitochondria may be depleted after TBI, with a physically smaller, MPT-regulated population remaining. Hippocampal mitochondria may sustain damage associated with ballooned membranes and reduced MPT pore calcium sensitivity. The heterogeneous mitochondrial response to TBI may underlie posttraumatic metabolic dysfunction and contribute to the pathophysiology of TBI.

Adenosine Triphosphate↗
PubMed2002

Intramedullary injection of contrast into the cervical spinal cord during cervical myelography: a case report.

STUDY DESIGN: A case of iatrogenic intramedullary contrast injection during a C1-C2 cervical myelography is reported. OBJECTIVE: To investigate the occurrence of iatrogenic intramedullary contrast injection during a current C1-C2 cervical myelography. SUMMARY OF BACKGROUND DATA: Intramedullary injection of contrast is a rare but serious complication of C1-C2 cervical myelography that has not been reported since the widespread use of magnetic resonance imaging and the NASCIS III study protocol. METHODS: A 39-year-old woman received an iatrogenic intramedullary contrast injection during a C1-C2 cervical myelography. RESULTS: During the procedure the patient reported right-side face, neck, and arm pain and parethesias. After the procedure, right arm weakness and diffuse hyperreflexia developed. Postmyelography imaging demonstrated intramedullary contrast and cord swelling. High-dose methylprednisolone was administered intravenously and the patient's symptoms improved. The literature and management of this rare complication are reviewed. CONCLUSIONS: Intramedullary cord injection is a rare complication of cervical myelography. The mechanism of spinal cord injury appears to involve a combination of physical compression from the injected liquid and neurotoxicity of the contrast material. Iohexol rather than metrizamide should be used when C1-C2 myelography is indicated in patients who are unable to undergo magnetic resonance imaging, or those whose pathology is inadequately demonstrated magnetic resonance imaging alone. In the event of contrast injection into the spinal cord, administration of high-dose methylprednisolone is recommended.

Adult↗
PubMed2002

February 2002: 29-year-old woman with a skull mass for 2 months.

A 29-year-old woman had a 2-month history of an enlarging lesion over her left frontal bone following minor trauma. CT scan showed an osteolytic lesion with an overlying soft tissue mass, thought to be an unhealed skull fracture with pseudomeningocele. Left frontal craniotomy revealed a soft tissue mass, which was resected. Histologic examination revealed multinucleated giant cells mixed with Langerhan's cells that showed the characteristic "coffee bean nuclei." Eosinophils were scant. Immunostaining for CD1a and S100 revealed strong positive staining primarily in the Langerhans' cells while giant cells and inflammatory cells were negative. Immunostaining for CD68, in contrast, stained the osteoclast-like giant cells and macrophages. Electron microscopy confirmed the presence Birbeck granules. The final diagnosis was Langerhans' cell histiocytosis (histiocytosis X) of the skull.

Adult↗
PubMed2002

Endovascular microcoil gene delivery using immobilized anti-adenovirus antibody for vector tethering.

BACKGROUND AND PURPOSE: Endovascular microcoils are widely used in interventional procedures to treat cerebral aneurysms. In the present study we report for the first time successful use of an endovascular microcoil as a gene delivery system. METHODS: Anti-adenoviral monoclonal antibodies were covalently attached to the collagen-coated surface of either platinum or polyglycolic acid microcoils. These antibodies were used to tether replication-deficient adenovirus (Ad-GFP [encoding green fluorescent protein] or Ad-LacZ [encoding beta-galactosidase]). Cell culture studies with rat arterial smooth muscle cells (A10) assessed transduction on or near the coil. Platinum coils coated with Ad-GFP were implanted into the ligated common carotid artery (CCA) of adult rats in a model of arterial stasis and pressurization. After 7 days, CCA segments were harvested, and coils were removed for histopathology and GFP expression studies, while organs were evaluated by polymerase chain reaction to assess viral biodistribution. RESULTS: In cell culture studies, GFP-positive smooth muscle cells were detected only on the platinum coil surface, while LacZ-positive cells were detected only on the polyglycolic acid coil surface, thus demonstrating localized gene delivery. After 7-day implantation, GFP (according to fluorescence microscopy and confirmed with immunohistochemistry) was detected on the harvested platinum coil and in the organizing thrombus within the CCA but not in the arterial wall. Morphometric analyses revealed that 13.3+2.0% of cells within the organized thrombus were transduced with Ad-GFP via the gene delivery system. However, arterial smooth muscle cells were negative for GFP according to fluorescence microscopy and immunohistochemistry. Ad-GFP was not detectable by polymerase chain reaction in lung, liver, or kidney. CONCLUSIONS: It is concluded that catheter deployment of platinum or biodegradable gene delivery endovascular microcoils represents an interventional device-based gene therapy system that can serve as a suitable platform for either single or multiple gene therapy vectors.

Adenoviridae↗
PubMedDate not supplied

Elevated intracranial pressures in spontaneous cerebrospinal fluid leaks.

BACKGROUND: Spontaneous cerebrospinal fluid (CSF) leak is a condition that previously has been considered idiopathic and classified as having "normal" intracranial pressure (ICP). We present clinical and radiographic evidence that indicates elevated ICP in this group. In addition, we review the pathophysiology and unique management issues in caring for patients with spontaneous CSF leak. METHODS: We present a retrospective review of medical records, imaging studies, ICP measurements, and surgical treatment of patients with spontaneous CSF leaks. RESULTS: Sixteen patients with spontaneous CSF leaks were surgically treated from 1996 to 2002. Ten patients underwent postoperative lumbar puncture with CSF pressure measurement during clinically indicated computed tomography cisternograms. Intracranial pressures were elevated in all 10 patients, with a mean of 26.5 cm H2O and a range of 17.3-34 cm H2O, (normal, 0-15 cm H2O). Demographically, 13/16 patients were women, all were middle-aged with a mean age of 49.6 years, and 15/16 patients were obese with a mean body mass index of 35.9 kg/m2. Radiographically, 15 patients had imaging of the sella turcica, 10 patients had completely empty sellas, and 5 patients had partially empty sellas. Surgical repair was 100% successful in leak cessation with a mean follow-up of 14.1 months. CONCLUSION: Although the precise cause and mechanism of spontaneous CSF leaks is not fully understood, this study sheds light on important factors to consider. Patients with this condition have similar physical and radiographic findings such as middle-aged, female gender, obesity, and empty sella. Additional investigation is needed to determine the exact cause of the condition, its relationship to elevated ICPs, and if further medical or surgical treatments to correct the intracranial hypertension are warranted.

Adult↗