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Biomedical subjects

R R Smith

Publications and source records attributed to R R Smith.

At least 19 recordsLinked to original sources

Solvation effects upon the thermodynamic substrate activity; correlation with the kinetics of enzyme catalyzed reactions. I. Effects of added reagents such as methanol upon alpha-chymotrypsin.

Solvents, detergents, etc., have often been added to the medium to study the kinetics of enzyme action and for binding studies. They have been employed for diverse reasons such as solubilization of substrates or to stabilize an enzyme that was originally membrane bound. Thermodynamic considerations dictate that any added substance, such as methanol, which is present in significant quantity must affect the thermodynamic activities of the enzyme, enzyme-substrate complex, substrate and any other intermediates although cancellation effects may occur in this regard. The influence upon substrate activities is the only one that is easily experimentally accessible. These effects are shown, from the data of Bernard and Laidler, to be large in the case of the alpha-chymotrypsin catalyzed hydrolysis of methylhydrocinnamate. The variation of the Michaelis-Menten constant is quantitatively explainable in terms of the alteration of the thermodynamic activity of the substrate by methanol.

Catalysis

Solvation effects upon the thermodynamic substrate activity; correlation with the kinetics of enzyme catalyzed reactions. II. More complex interactions of alpha-chymotrypsin with dioxane and acetone which are also competitive inhibitors.

It is shown that the effects of the addition of various amounts of dioxane and acetone (solvent modifiers) upon the alpha-chymotrypsin-catalyzed hydrolysis of methylhippurate can be explained in terms of three factors. (A) The effects of the above modifiers on the chemical potential of the substrate. (B) The solvent modifiers dioxane and acetone also act as classical competitive inhibitors. The means of sorting out these contributions is presented. (C) The alterations of the chemical potentials or for free energies of the enzyme, enzyme-substrate complex, and/or other intermediates by the added modifiers appear to cancel out with the substrate used here.

Acetone

Neuroradiology of intracranial infection.

The ability to detect and differentiate intracranial infection has markedly improved, first with the introduction of computed tomography and, more recently, with magnetic resonance. Enhanced magnetic resonance imaging is the procedure of choice in the evaluation of nearly all intracranial infections. The sensitivity of MR to foci of increased water content, seen in most parenchymal infections, the lack of bone artifact, and the multiplanar capability of MR have led to this preeminence. Computed tomography remains useful primarily in those infections associated with intracranial calcification, such as TORCH syndrome. This article summarizes the most recent CT and MR findings of infection involving the meninges and brain parenchyma.

AIDS-Related Opportunistic Infections

Mechanism of action of balloon angioplasty in cerebral vasospasm.

Recent technical advances in interventional neuroradiology have made it possible to dilate cerebral arteries showing vasospasm after a subarachnoid hemorrhage. Although the reported effects of dilatation in clinical cases have been dramatic, few experimental studies of the mechanism of action have been performed. It also is still unclear why dilated arteries rarely show restenosis. Using the scanning electron microscope, we examined changes in the three-dimensional structure of connective tissues in vessel walls after balloon angioplasty. Femoral arteries from cats and middle cerebral arteries from human autopsies were studied. The vessels were dilated in situ with a balloon catheter until the intimal pressure reached 1.5 Wr 3 atm; then they were fixed and digested with 88% formic acid. The specimens were freeze dried and observed under the scanning electron microscope. Normal vessels without balloon dilatation were treated in the same manner and used as controls. The results showed that the normal structure of collagen fibers in the vessel walls was affected significantly by balloon dilatation. Stretched and torn fibers were observed frequently when 3 atm were applied. We concluded that the long-lasting effects of balloon dilatation may be caused by the disruption of connective tissues that proliferate in the vessel wall after a subarachnoid hemorrhage.

Angioplasty, Balloon

Accelerated nonmuscle contraction after subarachnoid hemorrhage: culture and characterization of myofibroblasts from human cerebral arteries in vasospasm.

Cell culture lines from human cerebral arteries showing vasospasm after subarachnoid hemorrhage were established from three autopsy cases. Each culture line showed the ultrastructural characteristics of myofibroblasts. Decreased alpha-actin antigenicity, demonstrated using the anti-smooth muscle cell alpha-actin antibody, was observed in cultured cells possessing abundant F-actin. When incorporated into the three-dimensional collagen matrix in vitro, the cultured cells compacted the collagen lattice at a rate equivalent to that of human dermal fibroblasts. Lattice compaction was significantly accelerated by cerebrospinal fluid taken from patients with symptomatic vasospasm. Compaction was completely inhibited by the addition of 10(-6) mol/L verapamil or 100 U/mL heparin. Neither nimodipine (10(-5) mol/L) nor nicardipine (10(-5) mol/L) inhibited compaction, and endothelin (10(-6) mol/L) and potassium chloride (40 mmol/L) had no effect. The morphological change of cells in the collagen lattice suggests that both verapamil and heparin affect cellular motility, filopodial protrusion, and cell attachment. These data suggest that myofibroblasts in human cerebral arteries differ from medial smooth muscle cells and can generate a force rearranging the proliferated collagen matrix present after subarachnoid hemorrhage. This reorganization can contribute to, or be responsible for, sustained vasoconstriction. Consequently, current treatment for vasospasm may need to be reevaluated to include the nonmuscle components in the vessel wall.

Aged

Carbon dioxide reactivity in the evaluation of cerebral ischemia.

Carbon dioxide reactivity, as measured by transcranial Doppler, has been determined in a group of patients with carotid artery disease and compared to a control group. CO2 reactivity was readily evaluated using transcranial Doppler by having the patients breathe 5% CO2 via a rebreathing circuit. There were significant differences (P less than 0.01) between the symptomatic patients and asymptomatic controls, as well as between symptomatic and asymptomatic hemispheres (P less than 0.05) in the patients with carotid artery disease. Five patients had revascularization procedures with all showing improved CO2 reactivity in the symptomatic and asymptomatic hemispheres. The improvement occurred early in patients after carotid endarterectomy. Two patients demonstrated improved reactivity at 6 to 13 months after extracranial-to-intracranial bypass. Transcranial Doppler has proven to be an easily performed and repeatable method of evaluating CO2 reactivity and its response to treatment.

Administration, Inhalation

Lateral cervical spine dislocation and vertebral artery injury.

Although anterior and posterior traumatic displacement of cervical vertebrae are commonly noted, and the devastating neurological deficits associated with these injuries have been amply defined, lateral displacement with fractures has been rarely recognized, and the clinical significance of this injury has been overlooked. This report describes five cases of cervical spine fractures with lateral dislocation. All patients had lateral and anteroposterior cervical spine radiographs as well as cervical angiography or postmortem study demonstrating either complete occlusion or significant impairment of flow of the vertebral arteries. Two cases had traumatic vertebral artery occlusion with secondary medullary and cerebellar infarction resulting in the patient's death. Vertebral artery injury apparently is not uncommon in this particular type of fracture. The diagnosis of these vascular injuries may require angiography or magnetic resonance angiography. A vertebral occlusion or dissection is a problem of considerable complexity, requiring individualized management depending on the patient's symptomatology, location and nature of the injury, and time lapsed since the injury.

Adult

Leuko-araiosis: description and clinical correlates.

The term leuko-araiosis as predicted by Hachinski may now have outlived its usefulness. Careful delineation of the white matter changes seen in MR imaging by use of the MR characteristics and by the location of the lesions may reduce the apparent heterogeneity of the associate clinical and neuropathological findings. As currently defined, leuko-araiosis is seen in aggregate more commonly in subjects with cerebro-vascular disease or with cerebro-vascular risk factors but it is a common finding associated with aging in otherwise normal, healthy elderly subjects. Its clinical significance as an isolated finding in these populations should therefore be treated cautiously. Its appearance should alert the physician however to seek for and treat potential cerebro-vascular risk factors.

Alzheimer Disease

Direct surgery of the cavernous sinus: patient selection.

The cavernous sinus is involved either in lesions arising primarily in the sinus or in lesions invading the sinus from surrounding structures. Experience with direct surgery of the cavernous sinus is encouraging, but no conclusive evidence exists concerning the roles of conservative, surgical, and radiological treatments in terms of effectiveness, morbidity, and long-term results. Consequently, management is individualized according to the patient and the lesions. We discuss these factors in patient selection for cavernous sinus surgery.

Brain Neoplasms

The petrosal approach: indications, technique, and results.

Surgical access to the clivus and petrous apex remains a formidable challenge. Intradural tumours at the clivus and petroclival area are superbly exposed via the petrosal approach described here. To date, we have operated on 33 patients having benign tumours using this approach. Total removal was achieved in all patients except 3 with meningiomas. There was no mortality, morbidity included 1 patient with hemiparesis and several with cranial nerve deficits.

Brain Neoplasms

Adventitial red blood cells produce intimal platelet accumulation in cerebral arteries of cats following subarachnoid hemorrhage.

After dividing 21 cats into three equal groups, we exposed their right middle cerebral arteries transorbitally and adventitially irrigated them with 2 ml washed red blood cells, blood plasma, or saline. To determine arterial intimal platelet accumulation in each cat, we injected [111In]oxine-labeled platelets intravenously immediately before injecting the various experimental solutions. Animals were sacrificed 2 or 4 hours following the injection of labeled platelets. Irrigation with washed red blood cells produced a significantly greater intraluminal accumulation of platelets than irrigation with saline (p less than 0.05). Plasma tended to have less of an effect on platelet accumulation than washed red blood cells, but this difference was not significant. These data suggest that the adventitial blood fraction responsible for intimal platelet accumulation in cerebral arteries following subarachnoid hemorrhage may be derived mainly from the red blood cell fraction.

Animals

Effect of tissue plasminogen activator on intimal platelet accumulation in cerebral arteries after subarachnoid hemorrhage in cats.

Recombinant tissue plasminogen activator may be effective in preventing cerebral vasospasm after subarachnoid hemorrhage by resolving subarachnoid clots. We previously demonstrated that blood placed on the adventitial surface of cerebral arteries enhances intimal platelet accumulation, positively correlating with endothelial damage and other pathologic changes in vessel walls. In this study, we investigated the ability of a single bolus injection of tissue plasminogen activator to prevent platelet accumulation in cerebral vessels after subarachnoid hemorrhage. Subarachnoid hemorrhage was produced in cats by the transorbital intracisternal injection of 2.5 ml autologous arterial blood around the proximal part of the right middle cerebral artery. In 10 animals, 25 micrograms tissue plasminogen activator was injected at intervals of 10 (five cats) and 60 minutes (five cats) after subarachnoid hemorrhage. Intracisternal physiological saline (0.5 ml) was injected in six cats 10 minutes after subarachnoid hemorrhage. Platelets labeled with indium-111 were injected intravenously just before subarachnoid hemorrhage, and their radioactivity was measured in cerebral arteries at death. The results indicated that, after subarachnoid hemorrhage, early injection of tissue plasminogen activator inhibited intimal platelet accumulation, but later injection did not, although the extent of subarachnoid clot was reduced at both plasminogen injection times.

Animals

Pediatric brainstem glioma. Post-radiation clinical and MR follow-up.

Thirty-four pediatric patients, twenty with presumed and fourteen with biopsy or autopsy proven brainstem gliomas were imaged by CT and MR before radiation therapy. Twenty-eight patients received radiotherapy. Of these, eighteen fit the protocol for combined clinical and MR post-treatment evaluation. No cases of radionecrosis were seen at autopsy. This study shows that MR can demonstrate tumor response to radiation therapy, tumor progression prior to clinical deterioration, post-treatment cyst formation and hemorrhage. Although MR clinical correlation was not optimal on six week post-treatment evaluation, 4-10 month post-treatment MR scanning correlated well with clinical evaluation. MR appears useful in post-therapeutic monitoring of tumor response.

Adolescent