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Biomedical subjects

T A Duff

Publications and source records attributed to T A Duff.

At least 19 recordsLinked to original sources

Vertebrobasilar junction aneurysms associated with fenestration: treatment with Guglielmi detachable coils.

Three patients with vertebrobasilar junction aneurysms and associated fenestration were treated with Guglielmi detachable coils. The structure and hemodynamics of fenestrations may account for their frequent association with aneurysms. The complex hemodynamics of these aneurysms requires evaluation of both vertebral arteries. One treatment complication occurred but resulted in no deficit. All patients have returned to normal activity and remain healthy at 14 to 46 months.

Aged↗

Early treatment of ruptured aneurysms with Guglielmi detachable coils: effect on subsequent bleeding.

The major causes of mortality and morbidity in patients surviving the rupture of a saccular aneurysm are subsequent bleeding and vasospasm. The purpose of this study was to evaluate the influence of early treatment of ruptured aneurysms with Guglielmi detachable coils on the incidence of subsequent bleeding. Thirteen patients were treated within 72 hours of initial aneurysm rupture with Guglielmi detachable coils. Excluding three patients who died 2, 4, and 12 weeks after initial hemorrhage, all others have been followed up for intervals between 6 and 36 months (mean, 16 mo). None of these have had either clinical or radiographic evidence of subsequent bleeding. Assuming that there is a 30% incidence of subsequent bleeding in conservatively (nonsurgically) treated patients, the 0% subsequent bleed rate observed in this subgroup was significant at a P value of 0.01. Only one procedure-related complication occurred in this series, and 9 of 13 (69%) aneurysms were 100% occluded at the time of initial treatment. All aneurysms were at least 90% occluded at the end of initial treatment. In addition to reducing the risk of subsequent bleeding, early treatment facilitated the institution of an aggressive approach for management of both vasospasm and increased intracranial pressure. Patient outcome, as measured by the Glasgow Outcome Scale, was good in 9 of 13 (69%), poor in 1 of 13 (8%), and death in 3 of 13 (23%) patients. The results of this study suggest that early Guglielmi detachable coil treatment of ruptured aneurysms may be effective in reducing the incidence of subsequent bleeding and can be performed with a low incidence of complications.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The effect of hemoglobin and its metabolites on energy metabolism in cultured cerebrovascular smooth-muscle cells.

Cerebral arteries in spasm have been found to contain low levels of adenosine triphosphate (ATP), and it has been postulated that this change in levels results from hypoxia produced by arterial encasement in clotted material. This study was undertaken to determine whether any of four blood-derived agents, ferrous hemoglobin, methemoglobin, hemin, or bilirubin, is capable of reducing energy levels in cerebral artery smooth-muscle cells. Twenty-four-hour exposure of cultured canine basilar artery cells to ferrous hemoglobin and bilirubin led to a significant decline in ATP levels (to 8.9 nmol/mg protein and 2.8 nmol/mg protein, respectively) versus control (16.6 nmol/mg protein); methemoglobin and hemin showed no effect. Bilirubin but not hemoglobin was found to interfere with electron transport and with creatine phosphokinase activity in intact cells; however, bilirubin showed no inhibitory effect on this enzyme in cell-free conditions. The findings indicate that hemoglobin and bilirubin may be responsible for diminished energy levels in cerebral arteries. These observations also suggest that bilirubin may exert its effect on ATP by impairing mitochondrial function.

Adenosine Triphosphate↗

Bilirubin levels in subarachnoid clot and effects on canine arterial smooth muscle cells.

BACKGROUND AND PURPOSE: Previous studies have suggested that bilirubin is a potential contributor to cerebral vasospasm. The purpose of this investigation was to determine whether bilirubin accrues in subarachnoid clot, whether its vasoconstrictive effect could involve a direct action on arterial smooth muscle cells, and, if so, whether bilirubin affects their Ca2+ uptake. METHODS: Subarachnoid clots were analyzed for bilirubin using high-performance liquid chromatography. The length and 45Ca2+ uptake of vascular smooth muscle cells enzymatically dissociated from canine carotid arteries were measured before and after exposure to bilirubin solution. Additional experiments were conducted on cultured smooth muscle cells from canine basilar artery and on ATP-depleted cardiac myocytes. RESULTS: Mean +/- SE bilirubin concentration in experimental clot was 263 +/- 35.7 mumol/L. Vascular smooth muscle cells exposed to bilirubin showed progressive shortening (P < .01) and an increased uptake of 45Ca2+ (P < .001). Contraction was prevented by Ca(2+)-free media but not by verapamil. Experiments with heart myocytes showed that bilirubin caused an increased uptake of 45Ca2+ but not of [14C]sucrose. CONCLUSIONS: The results indicate that bilirubin accrues in subarachnoid clot, that it exerts a direct constrictive effect on arterial smooth muscle cells, and that this effect is associated with an increased uptake of Ca2+. Studies on heart myocytes suggest that the Ca2+ uptake induced by bilirubin could be due to a selective increase in membrane permeability to Ca2+.

Animals↗

Hemin: levels in experimental subarachnoid hematoma and effects on dissociated vascular smooth-muscle cells.

Although hemin is known to exert toxic effects on a variety of cell types, its possible participation in the genesis of cerebral vasospasm has received little attention. The authors measured the concentration of hemin in experimental subarachnoid clot and studied its effects on the morphology and 45Ca++ uptake of vascular smooth-muscle cells dissociated from canine carotid artery. Craniectomies were performed in five dogs under general anesthesia, and 3 to 5 ml of autologous whole blood was deposited in the supraclinoid subarachnoid compartment. The concentration of hemin recovered by Folch extraction from clotted material removed 7 days after surgery was 390 +/- 247 microM (mean +/- standard error of the mean). Mean vascular smooth-muscle cell length after 40 minutes of exposure to 50 microM hemin was 37.3 +/- 1.2 microns (control 51.6 +/- 1.6 microns) (p < 0.01). The mean percent permeation of 45Ca++, measured by a dual label technique, of cells exposed to hemin was 200.9% +/- 23% (control 102.9% +/- 4.3%) (p < 0.01). These findings indicate that hemin accrues in subarachnoid hematoma, that it exerts a constrictive effect on vascular smooth-muscle cells, and that this effect is associated with an increased uptake of Ca++. This study demonstrates that hemin should be included in the list of potential agents that participate in the development of cerebral vasospasm.

Animals↗

Surgical stabilization of cervical spinal fractures using methyl methacrylate. Technical considerations and long-term results in 52 patients.

This study analyzes the long-term outcome of 52 consecutively treated patients with acute cervical spinal fracture/dislocation who underwent posterior surgical stabilization using methyl methacrylate in the absence of bone grafting. The patients ranged in age from 15 to 93 years. In 40 patients the injury was located in the lower cervical spine; for these a previously described surgical format was employed. In 12 patients the fracture involved C-1 or C-2, and the modification used for these injuries is presented. The postoperative period of evaluation ranged from 6 months to 12 years. There was one case of infection, which eventually required removal of the acrylic, but there were no instances of new neurological injury or of operative mortality. Failure of stabilization occurred in two previously reported patients treated early in the series. Comparison of the patient outcome in this study with that of certain other reports suggests that at least four technical factors are important for the success of methyl methacrylate stabilization: 1) the acrylic inlay must be provided with an anchor to bone; 2) the anchor must be of a type that does not easily erode through bone; 3) the inclusion of wire must be done in a manner that allows each strand to be completely encased in the acrylic; and 4) the cross-sectional area of the inlay is critical.

Adolescent↗

Midline craniectomy for sagittal suture synostosis: comparative efficacy of two barriers to calvarial reclosure.

This report quantitatively compares long-term head remolding achieved by two methods for retarding bone reunion after midline craniectomy for sagittal suture synostosis. In one group of six children the adjacent bone edges were overlayed with 1.0-cm-wide U-channel silicone strips, and in the other group, composed of seven patients, a considerably larger extent of the adjacent cranium was covered with silicone sheets. Mean percent change in the cephalic indices of the former group 18 months postoperatively was 9.1% +/- S.D. = 6.7, and of the latter group 23.7% +/- S.D. = 6.0 (p congruent to 0.01). These results indicate that the use of large silicone sheets lead to a significantly greater normalization of cranial proportions.

Craniosynostoses↗

Intracranial arteriovenous malformations. Current imaging and treatment.

Patients with intracranial arteriovenous malformations (AVM) can expect significant mortality (15% to 20%) and morbidity (20% to 30%) over a 15-year to 20-year period. Recent advances in interventional neuroradiology, neurosurgery, neuroanesthesia, and stereotactic radiotherapy provide the opportunity to obliterate many of these lesions that were untreatable previously. The overall risk from treatment is estimated to be less than 50% that associated with untreated AVMs. For these reasons, it is important for the diagnostic radiologist to understand the diagnosis, natural history, treatment choices, and risks associated with patients with intracranial AVMs.

Craniotomy↗

Erythrocytes are essential for development of cerebral vasculopathy resulting from subarachnoid hemorrhage in cats.

In an effort to determine which blood elements play a critical role in the development of cerebral vasospasm, adult cats were subjected to prepontine injection of either autogenous whole blood or erythrocyte-free blood containing latex beads as a substitute morphologic marker. Seven or 10 days later the cats were anesthetized and perfused with fixative, and the basilar arteries were prepared for light and electron microscopy. Successful clot deposition was confirmed by the presence of numerous erythrocytes or latex beads within the adventitia of vessels. In agreement with previous studies, instillation of whole blood produced luminal narrowing associated with profound ultrastructural changes in all layers of the vascular wall. No significant alterations, however, occurred in arteries bathed in erythrocyte-free blood. These findings suggest first, that erythrocytes are essential for the development of the vasculopathy associated with chronic cerebral vasospasm, and second, that the role, if any, of other blood elements is not autonomous.

Animals↗

Bilirubin and the induction of intracranial arterial spasm.

Although a number of substances which participate in the physiological control of vascular caliber have been proposed to play a causative role in cerebral vasospasm, none of these has been shown to induce the profound, sustained degree of constriction or the vasculopathy that characterize this disorder. The present study was undertaken to determine whether bilirubin, a hemoglobin breakdown product with detergent-like activity, accrued in incubated blood or in intracranial hematoma and whether topical application of bilirubin altered the caliber or morphology of cerebral arteries. As a model of blood residing in the subarachnoid space, sterile vials of cat blood and of human blood were incubated in vitro at 37 degrees C. The concentration of bilirubin in the supernatant of cat blood increased from a value of 0.27 +/- 0.3 mg% (mean +/- standard error of the mean) on Day 0 to a value of 9.57 +/- 2.4 mg% on Day 10; the respective values for human blood were 0.53 +/- 0.02 mg% and 13.4 +/- 5.4 mg%. Samples of intracranial hematoma that had been surgically removed from three patients between 4 and 11 days after hemorrhage yielded bilirubin levels from 2.1 to 15.2 mg%. Application of a bilirubin suspension of 5, 10, or 20 mg% in buffered Ringer's solution to cat basilar artery in vivo led to progressive and sustained constriction; at 4 hours the mean decrease in the width of the blood column was 34% +/- 2.1%. Ultrastructural analysis of these vessels showed widespread pathological changes similar to those associated with cerebral vasospasm. Application of a 10-mg% bilirubin suspension to the basilar artery of two baboons produced similar alterations. Minimal changes in diameter or morphology were observed in cat arteries bathed in buffer solution alone. These findings in animal models indicate that bilirubin may play a central role in the development of cerebral vasospasm.

Animals↗

Surgical stabilization of traumatic cervical spine dislocation using methyl methacrylate. Long-term results in 26 patients.

Twenty-six patients with traumatic cervical spine fracture-dislocations had spinal stabilization with methyl methacrylate (acrylic) as the primary support. In most cases a 3/4-in. stainless steel screw was inserted into the articular pillars of the fractured vertebra and of the two adjacent vertebrae, followed by application of the acrylic in the form of an oblong mold over the heads of the screws. The follow-up period in these 26 patients ranged from 6 months to 7 years. There were no instances of wound infection or increased neurological impairment. Vertebral elements remained aligned in 25 of the 26 patients. Breakage of the acrylic support was documented in two patients, but in only one was surgical repair required. The results of this study indicate that the procedure is a safe and effective method for both immediate and long-term stabilization of cervical spine fracture-dislocations.

Adolescent↗

Ultrastructural evidence of arterial denervation following experimental subarachnoid hemorrhage.

Loss of catecholamine histofluorescence, increased sensitivity to norepinephrine, and changes in alpha1 receptor binding have led to the proposal that denervation hypersensitivity may play a role in cerebrovascular spasm. Because the significance of these alterations has remained unclear, the present study was undertaken to determine whether there was direct ultrastructural evidence of arterial denervation following experimental subarachnoid hemorrhage. Under general anesthesia, adult cats were subjected to pre-pontine injection of blood or serum (5 to 7 ml) via a transclival approach. The animals were sacrificed 4, 7, or 10 days later and basilar artery segments were prepared for electron microscopy. Control vessels appeared normal, whereas those bathed in blood revealed unequivocal changes in neural and supporting elements, including: 1) disintegration of both clear- and dense-core vesicles; 2) fragmentation of varicosities; 3) loss of Schwann cell cytoplasm; and 4) axonal degeneration. These changes were most pronounced 7 days after instillation of blood, and correlated in time with maximal injury of the media and endothelium. Although the development of smooth-muscle hypersensitivity remains unsettled, this study indicates that prolonged exposure to blood can cause extensive denervation of cerebral arteries.

Animals↗

Phase II trial of interferon-beta for treatment of recurrent glioblastoma multiforme.

Twelve patients were admitted to a Phase II study on the treatment of recurrent glioblastoma multiforme with interferon-beta (IFN-beta). All patients had previously undergone craniotomy and received a standard course of radiation therapy. Recurrence was inferred from enlargement of the lesion on computerized tomography (CT) scanning and in each case was confirmed by CT-guided stereotaxic biopsy. Treatment consisted of combined intravenous (10 X 10(6) IU/day) and intratumoral (1 X 10(6) IU every other day) administration of IFN-beta over three 10-day cycles. This regimen was well tolerated, with toxicity requiring temporary dose modifications in five patients. As judged from data from historical cases, however, the patients admitted to this study demonstrated no clear improvement in mean survival time. The findings of this study also emphasize the importance of distinguishing between radiation necrosis and tumor recurrence.

Adult↗

Regional differences in pigeon optic tract, chiasm, and retino-receptive layers of optic tectum.

Electron-microscopic examination of the pigeon optic chiasm, tract, stratum opticum, and retino-receptive layers of the optic tectum revealed regional differences at each level. Axonal size in the fiber pathways paralleled that previously reported for pigeon optic nerve, with mean diameter values of 0.96 micrometer for optic chiasm and 1.06 micrometer for optic tract. The dorsolateral aspects of these pathways contained a heterogeneous population of fibers (mean diameter congruent to 1.44 micrometer) similar to that found in the nasal portion of optic nerve, while the ventromedial regions were occupied by a more homogeneous population of smaller fibers (mean diameter congruent to 0.82 micrometer) resembling those observed in the temporal portion of the nerve. The retino-receptive layers of anteroventral optic tectum (avT) differed ultrastructurally from those of posterodorsal tectum (pdT) with respect to the thickness of horizontal dendrites in layer 2-3, the size of optic terminals in layers 2-7, and the number of synaptic contacts per terminal. These findings point towards a regional variation in the processing of visual information throughout the retino-tectal system and suggest that neurons in avT vs. pdT should show differences in the way they modify the neurophysiological characteristics of their respective optic inputs.

Animals↗