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Biomedical subjects

S C Jones

Publications and source records attributed to S C Jones.

At least 73 records · Page 4Linked to original sources
PubMed1991

Isovolumic hemodilution with dextran 40 in the rat: effect on the development of peripheral edema and various physiologic parameters.

Low molecular weight dextran 40 (D40), 40,000 daltons, is a potential therapeutic agent for cerebral ischemia because it increases local cerebral blood flow. However, the evaluation of D40 in the rat has been difficult due to systemic effects. We evaluated the effects of isovolumic hemodilution with D40 on the development of peripheral edema, mean arterial pressure, hematocrit (Hct) and total blood volume in 18 rats, during 30 min or 4 hr i.v. infusions, in animals with and without previous challenge with D40. Reduction of Hct without peripheral edema to a mean of approximately 31% was only achieved in the animals challenged with i.p. D40 24 hr before hemodilution and who received D40 over a period of 4 hr. Infusion of D40 over a period of 30 min was associated with shorter survival time, compared to the 4-hr infusion group (P less than .005). In the pretreated, rapidly infused group, total blood volume per body weight decreased significantly over time (P less than .005) and the mean arterial blood pressure dropped, but not significantly (P less than .07), whereas no change in Hct was detected and there was a trend toward increased peripheral edema, relative to the slowly infused groups. We conclude that reduction of Hct can be achieved successfully with i.p. administration of D40 24 hr before the study combined with infusion of the agent during a 4-hr period, without significant peripheral edema and early hypotension. This procedure should be used to avoid allergic reactions when evaluating hemodilution with D40 in rats.

Animals↗
PubMed1991

Abdominal migraine: does it exist?

Abdominal migraine is well recognised in children, but in spite of anecdotal reports migraine is not well established as a cause of abdominal pain in adults. Functional abdominal pain is usually classified as either irritable bowel syndrome or nonulcer dyspepsia, but some patients have intermittent abdominal pain associated with headache or other migraine accompaniments and, in these, a diagnosis of abdominal migraine should be considered. It is possible that some patients with functional abdominal pain have migraine presenting with few or even no migraine accompaniments. There is no nonclinical objective standard for diagnosing migraine, and research in this area is therefore very difficult. Nevertheless, some patients with functional abdominal pain may respond to antimigraine medication and, if their symptoms are suggestive, a trial of therapy may be desirable.

Abdominal Pain↗
PubMed1990

Optimal design of a thermistor probe for surface measurement of cerebral blood flow.

Microthermistors are put on the surface of cerebral cortex to monitor local cerebral blood flow (CBF) continuously with minimal tissue damage and disturbance to the normal physiological state. Using a distributed, dynamic model of the measurement system, we simulated the effects of this flow measurement method under isothermal and adiabatic boundary conditions. Numerical results show that the adiabatic boundary condition can provide maximal sensitivity to perfusion changes at physiological perfusion levels. The constant power and constant temperature operating modes are compared in terms of output relation, sensitivity, and frequency response through analytical and numerical solutions. While the steady-state relations between thermistor measurements and perfusion for the two modes do not differ significantly, the constant temperature mode has better frequency response. Analytical results show that the relative sensitivity is the same for the two modes and is approximately proportional to the radius of thermistor. If there is an unperfused layer surrounding the thermistor, the sensitivity will decrease as the thickness of the layer increases. Simulations predict that the thermal measurement has a low-pass frequency response and the cutoff frequency is inversely proportional to the probe surface area. The results provide a theoretical foundation to the optimal design of thermistor probe for continuous CBF measurement from tissue surface.

Cerebrovascular Circulation↗
PubMed1990

Epidermal growth factor binding and action on tympanic membranes.

A significant percentage of tympanic membrane (TM) perforations require some form of therapy to heal. Topical application of epidermal growth factor (EGF), a potent mitogen for epidermal and mesodermal cells, promotes healing of injuries in tissues histologically similar to TM, such as cornea and skin. We evaluated TM as a target tissue for EGF action. Specific, high affinity receptors for EGF were detected in TM (Kd = 3.1 nM, 150 fmol receptor/mg protein). Autoradiography of iodine 125-EGF binding to intact TMs revealed that EGF receptors were present on cells in the stratified squamous epithelial layer and in the stromal/mucoepithelial layer. Repetitive treatment of perforated cat TMs with 20 micrograms of EGF formulated in saline induced substantial hyperplasia of epithelial and stromal layers compared to paired TMs treated with saline. A single treatment of perforated cat TMs with 50 micrograms of EGF formulated in a hydrogel or in shredded Gelfoam produced significantly (p less than .05) smaller perforations at 6 days following the operation compared to paired TMs treated with vehicles. These results demonstrate that TM is a target tissue for EGF and that topical treatment with EGF stimulates healing of TM perforations.

Animals↗
PubMed1990

Vascular pressures and cortical blood flow in cavernous angioma of the brain.

This study was designed to investigate the hemodynamic characteristics of cavernous angiomas of the brain. Five adult patients with a cavernous angioma underwent local cortical blood flow studies and vascular pressure measurements during surgery for the excision of the cavernous angioma. Clinical presentation included headache in four patients, seizures in four patients, and recurring diplopia in one patient. Magnetic resonance imaging demonstrated the cavernous angiomas in all patients and revealed an associated small hematoma in two. Four patients with a cerebral cavernous angioma were operated on in the supine position and the remaining patient, whose lesion involved the brain stem, was operated on in the sitting position. Mean local cortical blood flow (+/- standard error of the mean) in the cerebral cortex adjacent to the lesion was 60.5 +/- 8.3 ml/100 gm/min at a mean PaCO2 of 35.0 +/- 0.6 torr. Mean CO2 reactivity was 1.1 +/- 0.2 ml/100 gm/min/torr. The local cortical blood flow results were similar to established normal control findings. Mean pressure within the lesion in the patients undergoing surgery while supine was 38.2 +/- 0.5 mm Hg; a slight decline in cavernous angioma pressure occurred with a drop in mean systemic arterial blood pressure and PaCO2. Mean pressure in the cavernous angioma in the patient operated on in the sitting position was 7 mm Hg. Jugular compression resulted in a 9-mm Hg rise in cavernous angioma pressure in one supine patient but no change in the patient in the sitting position. Direct microscopic observation revealed slow circulation within the lesions. The hemodynamic features demonstrated in this study indicate that cavernous angiomas are relatively passive vascular anomalies that are unlikely to produce ischemia in adjacent brain. Frank hemorrhage would be expected to be self-limiting because of relatively low driving pressures.

Adult↗
PubMed1989

Bimodal treatment with nimodipine and low-molecular-weight dextran for focal cerebral ischemia in the rat.

We compared the effects of intravenous treatment with combined low-molecular-weight dextran and nimodipine (n = 9), or placebo (n = 10), on local cerebral blood flow after occlusion of the left middle cerebral and common carotid artery in the rat. Treatment for a total of 4 hours with low-molecular-weight dextran (5 mg/kg/min) and nimodipine (0.25 microgram/kg/min) produced a decrease in hematocrit from 46 +/- 1 to 33 +/- 1% at the end of the study and a statistically significant increase in local cerebral blood flow, when compared to the control group, in 6 regions of interest: the territories of the right middle (p = 0.01), right anterior (p = 0.007), and left anterior cerebral arteries (p = 0.001); the superior (p = 0.03) and inferior border zone (p = 0.003); and white matter in the right hemisphere (p = 0.04). The ischemic volume, defined as brain volume with a cerebral blood flow of less than the critical level of 25 ml/min/100 gm was determined as a percentage of total brain volume for the control and treatment groups. The group treated with low-molecular-weight dextran and nimodipine showed a 31% decrease in ischemic volume (p = 0.03). These results indicate that a bimodal approach with low-molecular-weight dextran and nimodipine can be safely used in a model of acute stroke and has a beneficial effect on local cerebral blood flow and ischemic volume when compared with control subjects. After 4 hours, the potential exists that this treatment is therapeutic, assuming that the ischemic volume progresses to infarction.

Animals↗
PubMed1989

CO2 reactivity and heterogeneity of cerebral blood flow in ischemic, border zone, and normal cortex.

Regional arterial CO2 tension (PaCO2) reactivity of cerebral blood flow (CBF) and the effect of PaCO2 on the spatial and temporal heterogeneity of CBF were investigated by using autoradiographically determined CBF in the rat middle cerebral artery occlusion model after a 2-h period under pentobarbital anesthesia to clarify the relation between PaCO2 reactivity, CBF heterogeneity, and the temporal cycling of CBF. PaCO2 was adjusted to one of four levels. CBF was determined in four cortical areas and white matter using the tissue fractionation of [14C]iodoantipyrine [( 14C]IAP) in combination with vessel mapping using in vivo 4% thioflavine S. Specific PaCO2 reactivity and CBF were normal in the nonischemic cortex, normal, although slightly depressed, in the border zone far from the ischemic core area, and depressed in the border zone adjacent to the ischemic core area (P less than 0.001) and the ischemic core (P less than 0.001). In normocapnic and hypocapnic animals, CBF heterogeneity in the form of regularly spaced CBF columns perpendicular to the cortical surface was observed in the nonischemic hemisphere but was absent in the ischemic core area. In hypercapnic rats, flow columns were present in the ischemic core areas and border zones but were absent on the nonischemic side. There was a highly significant interaction (P less than 0.0001) in observer-determined heterogeneity grades between PaCO2 level and each of three areas, normal, border zone, and ischemic core. In normal cortex, comparison of the thioflavine S-stained vessels with the flow columns provided evidence supporting the concept of capillary recruitment and cycling as a mode of normal cerebral blood flow control. The presence of flow columns in severely ischemic areas in hypercapnic animals indicates that a short period of high PaCO2 transiently augments microregional flow and could enhance the delivery of a therapeutic agent to these microregions of the ischemic core. The regional analysis of PaCO2 reactivity suggests an index of future tissue viability.

Animals↗
PubMed1988

Kinetic independence between red cell anion exchange and urea transport.

Urea equilibrium exchange fluxes were measured in human red cells under conditions which recruit the anion transporter into an outward-facing or an inward-facing state (with respect to the anion transport site). Regardless of these conditions, urea transport always occurred at the same rate: 41 +/- 2 mol.(kg cell solids.min)-1 with 1.5 M urea at 0 degrees C. These data suggest that the pathway on the band-3 protein which mediates anion transport is kinetically uncoupled from urea transport and is probably not involved in the transport of urea across the red cell membrane.

Anion Exchange Protein 1, Erythrocyte↗
PubMed1988

The evaluation of quantitative autoradiogram processing systems for cerebrovascular research.

The development of an image processing system for quantitative autoradiography (QAR) is described, with emphasis on the evaluation of image digitization systems independent of hardware or software design. Each step of converting the autoradiographic image to a functional image of a physiological variable such as local cerebral blood flow (LCBF) or local cerebral glucose utilization rate (LCGU) is evaluated. The autoradiograms are digitized, aligned, transformed to a tissue tracer concentrations image based on the gray value (GV) of calibrated 14C standards, subtracted from each other as required in double tracer QAR, and converted to an LCBF or LCGU image using the proper tracer kinetic model. Geometric size, mean and standard deviation of the LCBF, LCGU, and tracer concentration can be measured in regions of interest. These steps are evaluated separately for their contribution to the accuracy and precision of the final, functional image. The qualities important in the final image are spatial resolution, intensity linearity, and intensity sensitivity, as well as the noise level. Techniques for evaluating the LCBF image include: (1) optimization of the input linearity and dynamic range of the video camera to maximize relative intensity sensitivity of the final functional image; (2) visual inspection of the curves used to fit various functions that are important in the conversion of the GV image to an image of physiological interest; (3) consideration of the noise introduced by the input devices and during the image conversion; and (4) above all, the integration of the various parts of the system to produce an accurate image useful in cerebrovascular research.

Autoradiography↗
PubMed1988

Evolving focal cerebral ischemia in cats: spatial correlation of nuclear magnetic resonance imaging, cerebral blood flow, tetrazolium staining, and histopathology.

The spatial correlation of nuclear magnetic resonance imaging (NMRI) and cerebral blood flow (CBF) may improve our ability to identify ischemic brain lesions and may provide further insight into the pathophysiology of early cerebral ischemia. Eleven pentobarbital-anesthetized adult cats underwent exposure of the common carotid arteries bilaterally and the right middle cerebral artery through a transorbital approach. Baseline NMRI images were obtained with a single spin-echo, multislice technique using a 0.6-T field, 0.4-cm slice thickness, and a surface coil. Focal ischemia was produced with right middle cerebral artery occlusion and potentiated with bilateral common carotid artery ligation. Sequential NMRI studies were then performed at 1, 2, 4, 6, and 12 hours or until CBF was determined in the same cats using [14C]iodoantipyrine at either 2 (n = 2), 4 (n = 2), 6 (n = 2), or 12 (n = 1) hours after the time of occlusion. This protocol allowed temporal and spatial correlation of NMRI and CBF. Alternate 5-mm brain slices were incubated with 1% 2,3,5-triphenyltetrazolium chloride (TTC) for 45 minutes at 37-41 degrees C and frozen in liquid Freon for later autoradiographic CBF determination. Four cats were studied only with NMRI and TTC (not CBF). The correlation between areas of increased NMRI signal intensity observed in T2-weighted images (repetition time 2,000 msec, echo time 120 msec), vital staining with TTC, low CBF, and routine histology was evaluated. During the early phase (less than 6 hours), T2-weighted NMRI changes were localized to the central ischemic gray matter areas, as defined in the later CBF images, with no involvement of the white matter. By the twelfth hour the NMRI changes involved the entire ischemic area including gray and white matter. The initial visible changes seen on T2-weighted NMRI are suggestive of cellular edema, and the later changes are characteristic of vasogenic edema. The spread of NMRI changes compared with the ischemic area determined from autoradiographic CBF is consistent with the previously described biphasic evolution of ischemic injury. These data suggest that T2-weighted NMRI could be used clinically to delineate areas of acute ischemic stroke.

Animals↗
PubMed1988

Altered cerebral autoregulation and CO2 reactivity after aneurysmal subarachnoid hemorrhage.

Disruption of local cortical blood flow (CBF) autoregulation and CO2 reactivity, or vasoparalysis, has been documented in humans after aneurysmal subarachnoid hemorrhage (SAH). Generally, the degree of vasoparalysis is related to the patient's clinical grade. Using intraoperative measurement of local CBF, we evaluated pressure autoregulation and CO2 reactivity in patients after SAH. Fourteen patients with SAH and 10 patients with asymptomatic aneurysm underwent craniotomy for clipping of their aneurysms. During operation, local CBF was recorded with thermal conductivity probes placed on the middle frontal gyrus, 4 to 6 cm from the nearest point of retraction. Before retractor placement, CBF was measured with the PCO2 at 25 and 35 mm Hg and the mean arterial blood pressure (MABP) between 70 and 80 mm Hg. After aneurysm clipping, flows were again measured. With the PCO2 at 25 mm Hg, the MABP was raised from 65 to 85 mm Hg. The PCO2 was then allowed to rise to 35 mm Hg, after which the MABP was lowered from 85 to 65 mm Hg. Six patients underwent operation within the 1st week after SAH (Grade I, n = 3; Grade II, n = 3). The remainder (n = 8) were operated on 9 days to 3 months after SAH. After aneurysm clipping, significant CBF changes (P less than 0.001) with PCO2 alteration occurred in control patients and those operated on more than 7 days after SAH. There was no significant change in CBF in patients operated on within 7 days after SAH. Changes in CBF reactivity to alteration of MABP were significantly larger in early operation patients than in other groups (P less than 0.008).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Denaturation of a membrane transport protein by urea: the erythrocyte anion exchanger.

Chloride equilibrium exchange was measured in the presence of intracellular and extracellular urea, several different alkylureas and thiourea. Urea half-inhibited Cl exchange at about 2.5 M, but the other, less polar analogs had significantly higher potencies; e.g., butylurea half-inhibited at about 60 mM. Onset and reversal of inhibition occurred within less than 2 sec. The inhibition exhibited no obvious sigmoidal dependence on urea concentration, and at low concentrations dimethylurea was a noncompetitive inhibitor of Cl exchange. However, at higher concentrations the Dixon plots were curved upward and a Hill analysis of the dimethylurea data yielded a Hill coefficient of at least 1.5. When present on only one side of the membrane, the slowly penetrating thiourea inhibited Cl exchange with a higher potency from the outside of the cell. Cl/Br exchange was inhibited less under conditions of self-inhibition of anion exchange than in the absence of self-inhibition. These data indicate that the ureas inactivate the anion transporter by a reversible denaturation process, and that the function of the anion transport mechanism may be more sensitive to small perturbations of protein structure than are spectroscopically derived structural parameters.

Anion Transport Proteins↗
PubMed1987

[14C]iodoantipyrine and microsphere blood flow estimates in cat brain.

A comparison of local cerebral blood flow estimates with the microsphere and the 4-[N-methyl-14C]iodoantipyrine ([14C]IAP) techniques has been performed in cats. Good correlation of [14C]IAP with microsphere flow estimates in the gray matter was found. In the white matter, however, [14C]IAP flow estimates were consistently lower than microsphere flow estimates. Error analysis of both techniques and comparison with previous studies suggest that peculiarities of white matter arterial vasculature with preferential microsphere accumulation may lead to this discrepancy. Microspheres did not interfere with flow as shown by the normal appearance of subsequent [14C]IAP autoradiograms. The number of microspheres seen on autoradiograms was used for an estimate of microvessels blocked by spheres and found to be negligible. The study also demonstrates that [14C]IAP is not diffusion limited up to the observed flow values of 2 ml.g-1.min-1. Both techniques might be used together for a combination of their respective advantages, which are temporal and spatial resolution for microsphere and [14C]IAP, respectively.

Animals↗
PubMed1987

Cerebral circulation during arteriovenous malformation operation.

The circulatory changes in the cortex around a cerebral arteriovenous malformation (AVM) were studied in 18 patients. The AVMs had rapid circulation times with early draining veins on angiography. Local cortical blood flow (lCoBF) was measured with cortically applied thermister/Peltier stack arrays. The AVMs had a more pronounced effect on lCoBF at a 2- to 4-cm distance from the AVM margin than in the adjacent cortex. Mean preexcision lCoBF was 62.9 +/- 6.7 (SE) ml/100 g/minute (i.e., similar to normal controls) near the AVM margin and 43.0 +/- 4.2 ml/100 g/minute far (i.e., greater than 2 cm) from the AVM. CO2 reactivity (COR) before excision was 1.1 +/- 0.3 ml/100 g/minute/torr of CO2 (i.e., similar to normal controls) at near sites and 0.6 +/- 0.3 ml/100 g/minute/torr of CO2 at far sites. The mean postexcision near lCoBF remained stable at 55.8 +/- 5.1 ml/100 g/minute at near sites, but the far lCoBF significantly increased (P less than 0.05) to 57.2 +/- 6.8 ml/100 g/minute. The cortical feeding artery pressure was substantially below the normal cortical artery pressure in 50% of the cases studied. Pressure in these arteries normalized after occlusion and AVM excision, resulting in a rapid increase in cortical artery perfusion pressure. Draining red vein pressure, which was elevated before AVM excision, also dropped after excision, contributing to the increase in perfusion pressure. Two patients who developed the normal perfusion pressure breakthrough syndrome (PBS) after operation had low lCoBF and disturbed COR before AVM excision and marked increase of lCoBF after excision.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1985

Effect of iodoacetate on local cerebral blood flow and glucose metabolism in cats: a double-radionuclide autoradiographic study.

The effect of iodoacetate (IAA), an inhibitor of glycolysis, on local CBF (LCBF) and local CMRglu (LCMRglu) was studied in cats by means of a double-radionuclide autoradiographic method. Artificial CSF containing 5 mM IAA was superfused on the left parietal cortex under a cranial window for 30 min. [14C]2-Deoxyglucose and [123I]iodoantipyrine were injected for the determination of LCMRglu and LCBF, respectively. A marked increase in LCBF, accompanied by a moderate to severe depression of LCMRglu, was observed in the IAA-superfused cortex. This result suggests that LCBF may be closely regulated by the cellular energy state associated with glycolytic activity in brain tissue.

Animals↗
PubMed1985

Evaluation of a double-tracer autoradiographic technique for the measurement of both local cerebral glucose metabolism and local cerebral blood flow.

A solvent washout technique is evaluated that could be used to remove one 14C tracer after a combined autoradiographic CMRglu and CBF study using [14C]2-deoxyglucose (2DG) and [14C]iodoantipyrine (IAP). The technique permits the simultaneous measurement of local CBF and local CMRglu in the same animal without the use of the short-lived tracers of iodine, 123I and 131I, for iodoantipyrine labeling. This report shows that brain tissue sections did not retain 14C from [14C]2DG when chloroform was used as the washout solvent. Chloroform washing removes nearly all the 14C from [14C]IAP. For this study, careful attention was given to the control, prewash measurement of 14C concentration.

Animals↗
PubMed1985

Cerebral blood flow with the continuous infusion of oxygen-15-labeled water.

This work describes the determination of CBF in eight normal human subjects with positron emission tomographic (PET) imaging using the continuous intravenous infusion of H2(15)O. A whole-brain CBF model is described that permits the comparison of the CBF values determined using PET with those obtained using other methods. This model includes a correction for whole-brain recovery coefficient, a correction for the underestimation of flow due to the nonlinearity of the CBF model when considering tissue that includes both gray and white matter, the use of in vitro-determined brain-blood partition coefficients for gray and white matter, and a variation of the equilibrium model that permits the arterial concentration to vary. CBF values using this method compare well with values determined previously. Regional determinations using a brain overlay atlas are presented. Radiation dosimetry for the continuous infusion of H2(15)O is also included.

Adult↗