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Biomedical subjects

J R Little

Publications and source records attributed to J R Little.

At least 55 records · Page 3Linked to original sources

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↗

Patch angioplasty in carotid endarterectomy. Advantages, concerns, and controversies.

There is much controversy in the literature regarding the precise role of patch angioplasty in carotid endarterectomy. Our report summarizes the theoretical and experimental considerations, including the hemodynamic effects and biologic behavior of the graft, associated with this technique. We present a detailed review of the literature regarding the clinical efficacy of patch angioplasty in carotid endarterectomy, including the early results, the late results, and the incidence and nature of carotid restenosis. We address concerns about the use of patch angioplasty, including the duration of cross-clamping, potential problems with the graft and suture-line disruption, and graft atherogenesis. We conclude that most recent literature indicates that patch angioplasty decreases acute complications (notably carotid occlusion) after carotid endarterectomy and prevents or delays carotid restenosis. As pressure increases to achieve a minimal rate of perioperative morbidity, many surgeons are expected to adopt patch angioplasty in more of their cases. However, in the absence of conclusive results from a prospective randomized study, opinion will continue to be divided regarding the routine versus the selective use of patch grafting in carotid endarterectomy. We present criteria for randomized trials of this technique.

Animals↗

Spinal cord compression: a complication of silicone-coated Dacron dural grafts. Report of two cases.

Two case reports of compression of the cervical spinal cord associated with silicone-coated Dacron dural grafts are presented. In both cases, the cervical spinal cord was distorted and compressed by an intense tissue reaction that encapsulated the synthetic graft. At least two factors are thought to play a role in precipitating this reaction: (1) the introduction of surface contaminants into the wound, and (2) repeated motion at the graft site.

Adult↗

Early carotid endarterectomy after cerebral infarction.

The objective of the study was to review our recent experience with carotid endarterectomy performed within 30 days of completed cerebral infarction and to evaluate the role of computed tomographic (CT) scanning in the decision-making process. Twenty-seven of 302 operations (9%) were carried out during the 30-day time period. The mean interval between cerebral infarction and surgery was 14 days. Angiography revealed severe stenosis (greater than 75%) of the internal carotid artery in 19 patients. Severe stenosis with deep ulceration found in 6 patients and moderate stenosis (i.e., 50-75%) with deep ulceration was found in 2 patients. CT scans showed recent infarction in 4 patients and an old subcortical lacune in 2 patients. Twenty-two patients were neurologically stable with mild deficits and showed normal results on a CT scan performed 24 hours or more after the ischemic event. These patients underwent early cerebral angiography and carotid endarterectomy without permanent morbidity or mortality. Two patients with moderate stable neurological deficits and findings of recent infarction on CT scans had uneventful postoperative courses. Five patients who were neurologically unstable underwent surgery. The 2 patients with repeated transient ischemic attacks and normal findings on CT scans had uneventful postoperative courses. Two of the three patients with progressive neurological deficits and CT findings of recent cerebral infarction experienced extension of their infarcts after surgery. One of these patients died. Our personal experience, together with a review of previous reports, indicated that patients who have minimal residual neurological deficits and whose CT scans show normal findings are at low surgical risk, perhaps approaching that of patients with transient ischemic attacks.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain Ischemia↗

Intracranial meningiomas in the aged: surgical outcome in the era of computed tomography.

Seventy-five patients older than 60 years of age underwent surgical resection of intracranial meningiomas during a 10-year period at a single institution. All patients had a computed tomographic scan preoperatively, and all were followed for at least 3 months postoperatively. There were 50 patients 61 to 70 years of age (Group A), and 25 patients older than 70 years (Group B). Sixteen patients (21%) were asymptomatic, and no patient was severely disabled preoperatively. Operative morbidity and mortality and outcome at 3 months were assessed and correlated with age, preoperative neurological status, and tumor size and location. Operative mortality was 6.6% (6% in Group A; 8% in Group B). Perioperative morbidity (including medical and surgical complications and worsening in neurological status) was 48% (46% in Group A; 52% in Group B). Neurological status 3 months after surgery was improved by at least one grade as compared to before surgery in 40% of patients (38% in Group A; 44% in Group B), unchanged in 29% (34% in Group A; 20% in Group B), and worsened in 31% (28% in Group A; 36% in Group B). While nearly half of the patients were asymptomatic 3 months after surgery, 11 patients (15%) had died or remained seriously disabled. Outcome at 3 months correlated significantly with low neurological grade preoperatively and with a tumor location over the cortical convexity. There was no significant correlation with age or tumor size. We conclude that resection of intracranial meningiomas is associated with significant morbidity and mortality in the elderly.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

The effect of subarachnoid hemorrhage on blood and CSF atrial natriuretic factor.

Atrial natriuretic factor (ANF) is a diuretic natriuretic peptide hormone produced by both the heart and brain which has been postulated to play a role in the hemodynamic and sodium instability that frequently follows subarachnoid hemorrhage (SAH). Levels of ANF were measured in 12 patients with nontraumatic SAH and nine control patients with unruptured cerebral aneurysms. At surgery, the mean plasma ANF level (+/- standard deviation) of the SAH group was significantly higher than that of the control group (158.1 +/- 83.8 vs. 57.8 +/- 45.3 pg/ml, respectively; p = 0.01). There was no significant difference in serum sodium concentration, blood pressure, or central venous pressure between these groups. Nine patients with SAH due to aneurysm rupture had plasma ANF levels similar to those in three patients with SAH due to other causes. Four patients with moderate to severe SAH had significantly higher mean cerebrospinal fluid (CSF) ANF values (17.7 +/- 12.8 pg/ml) than five patients with minimal SAH (0.6 +/- 0.9 pg/ml) or the control group of nine patients (3.7 +/- 1.3 pg/ml) (p less than 0.05). Five patients with moderate to severe SAH had significantly higher plasma ANF values (202.6 +/- 72.2 pg/ml) than five with minimal SAH (86.8 +/- 29.2 pg/ml) or the control group (57.8 +/- 45.3 pg/ml) (p less than 0.05). Plasma ANF values were substantially higher than CSF ANF content in the SAH group (p less than 0.01) and in the control group (p = 0.05). From these data it is concluded that: 1) plasma ANF is elevated significantly after SAH; 2) this rise appears unrelated to the cause of hemorrhage, serum sodium concentration, blood pressure, or central venous pressure, but is related to the extent of the hemorrhage; 3) ANF concentrations in the CSF are significantly lower than in plasma, and are elevated after moderate to severe SAH; and 4) the source of CSF ANF is probably the plasma, and the source of plasma ANF is likely the heart.

Adult↗

The safety of cumulative doses of labetalol in perioperative hypertension.

Intravenous labetalol is commonly used in the management of hypertensive emergencies or urgencies as well as postoperative hypertension. The maximum recommended dose in any clinical setting is 300 mg in 24 hours. The safety of administering high doses of intravenous labetalol (greater than 300 mg in 24 hours) was evaluated in neurosurgical patients (n = 9). During 15 distinct periods of 24 hours or less, the mean dose of labetalol given was 623 +/- 86 mg. Adverse hemodynamic and biochemical effects were minor and easily reversible. Intravenous labetalol can safely be used in doses exceeding 300 mg per 24 hours in neurosurgical patients.

Adult↗

Labetalol to control blood pressure after cerebrovascular surgery.

Fifteen patients who had undergone neurovascular surgery for arteriovenous malformations or cerebrovascular aneurysms and had intracranial pressure (ICP) monitors were studied. The patients had been treated initially with sodium nitroprusside to maintain their arterial BP in a prescribed range, but, because of excessive nitroprusside dose requirements, they were considered either to have refractory BP or to be at risk for thiocyanate toxicity. Intravenous labetalol therapy was started either by frequent bolus pulse therapy every 1 to 2 h or by continuous infusion therapy. The degree of desired arterial BP control and the effects on ICP and cerebral perfusion pressure (CPP) were assessed and compared with the results during nitroprusside therapy. The degree of arterial BP control with labetalol was assessed to be good; 11 patients were weaned off nitroprusside and the remaining four patients had a substantial reduction in their nitroprusside requirements, needing an average of only 1.5 micrograms/kg.min of nitroprusside to control their BP compared with average requirements of 10 micrograms/kg.min of nitroprusside before labetalol therapy. Labetalol therapy improved CPP in six patients and ICP in five patients, with no significant change in cerebral pressure in the remainder. Overall, the CPP in the 15 patients improved from 63 +/- 15 (SD) mm Hg with nitroprusside to 65 +/- 10 mm Hg with labetalol therapy and the ICP decreased from 11.3 +/- 6.1 mm Hg with nitroprusside to 8.6 +/- 3.1 mm Hg with labetalol therapy (p less than .05 by Wilcoxon matched pairs).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

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↗

Giant and multiple aneurysms of the distal posterior inferior cerebellar artery.

A case involving giant and multiple aneurysms of the distal posterior inferior cerebellar artery (PICA) is presented. Of the 130 reported cases of peripheral aneurysms of the PICA, 6 have been described as giant aneurysms and 5 have involved multiple aneurysms located on a single PICA. The occurrence of multiple aneurysms including one giant aneurysm has not been reported previously. A clinical description of our case as well as a review of the literature is presented.

Cerebellum↗

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↗

Postoperative hemorrhage: a survey of 4992 intracranial procedures.

A series of 4992 intracranial procedures performed over an 11-year period was evaluated for the occurrence of postoperative hemorrhage. Forty patients (0.8%) experienced postoperative hemorrhage. Twenty-four hemorrhages were intracerebral (60%), 11 were epidural (28%), 3 were subdural (7.5%), and 2 were intrasellar (5.0%). Hematomas in 33 patients occurred at the operative site, and 7 occurred remote from the operative site. Intracranial tumor was the reason for operation in 56% of the patients developing a clot, and meningioma was the most common tumor associated with this complication. The use of the sitting position was not associated with an increased incidence of postoperative hemorrhage. Disturbances of coagulation and hypertension seemed to be potential precipitating factors. Postoperative hemorrhage was recognized within 12 hours of operation in 35% of the patients. An altered level of consciousness was the most frequent clinical finding, present in all patients. There was no clear relationship between the time of recognition and the final clinical outcome. Parenchymal clots carried the worst prognosis, accounting for 8 of the 11 deaths and all 7 patients with poor neurological outcome.

Adolescent↗

Modulation of the macrophage oxidative burst by Histoplasma capsulatum.

The production of reactive oxygen species by phagocytic cells is an important host defense against invading microorganisms. Because pathogens that achieve intracellular survival escape destruction by reactive oxidants, we investigated the relationship between the intracellular survival of H. capsulatum and the macrophage oxidative burst. H. capsulatum yeast failed to stimulate the release of reactive oxygen metabolites in unprimed murine macrophages despite extensive phagocytosis of the microorganisms. This effect was observed with live as well as heat-killed fungi over a wide range of yeast-to-macrophage ratios. Preincubation of murine macrophages with heat-killed H. capsulatum (but not with latex spheres), followed by incubation with unopsonized zymosan, resulted in inhibition of oxidative burst triggering without inhibition of zymosan phagocytosis. Ingestion of H. capsulatum yeast opsonized with the cognate mouse antibody resulted in significant oxidant release, suggesting that suppression of the respiratory burst may be circumvented through Fc-mediated phagocytosis.

Animals↗

Parallel inheritance of tissue catalase activity and immunostimulatory action of amphotericin B in inbred mouse strains.

Both amphotericin B (AmB) and its methyl ester derivative are potent immunoadjuvants that also stimulate murine B lymphocytes and macrophages in vitro. Most of the common inbred mouse strains show AmB-induced immunostimulation (AmB-high responders) but mice from the C57BL strains, regardless of H-2 genotype, are AmB-low responders. Lymphoid cells from AmB-high responder strains also exhibit greater resistance to H2O2 toxicity in vitro compared with cells from AmB-low responders. This result led to an evaluation of differences in the tissue catalase levels of AmB-high and -low responder strains. Results from several laboratories, including ours, indicate that C57BL mouse strains express low levels of tissue catalase activity in addition to low or absent immunostimulant effects of AmB. Several AmB-high responder strains have high spleen cell, macrophage, and liver catalase, and the mouse strain distribution of enzyme activity as well as the dominant inheritance of the low catalase phenotype is compatible with regulation by the Ce-1 locus in lymphoid organs as well as liver. Other evidence also suggests that H2O2 metabolism is important in lymphoid cell responses to AmB. For example, AmB stimulates a stronger respiratory burst in macrophages from AmB-high responder strains under the same conditions that inhibit burst activity in macrophages from low responders. Selective immune enhancement by AmB in high catalase mouse strains along with enhanced susceptibility to AmB toxicity in low responder C57BL mice with low tissue catalase activity suggests that cellular peroxidation is a major determinant of the genetic regulation of amphotericin-induced immunostimulation.

Amphotericin B↗

Electrophysiological monitoring during basilar aneurysm operation.

Intraoperative brain stem auditory evoked potential (BAEP) and somatosensory evoked potential (SEP) monitoring was evaluated in 16 patients each undergoing intracranial operation for basilar artery aneurysm. The 16 patients had 18 posterior circulation aneurysms, including 2 patients with 2 aneurysms. Fourteen aneurysms arose from the rostral basilar artery, 2 arose from the midbasilar artery, 1 arose from the vertebrobasilar junction, and 1 arose from the proximal segment of the posterior cerebral artery. Five aneurysms were classified as giant (i.e., greater than 25 mm), and 5 aneurysms were large (i.e., 15 to 25 mm). Ten patients had BAEP and SEP monitoring, 4 had BAEP monitoring only, and 2 had SEP monitoring only. Two patients showed significant abnormalities during operation, including 1 patient with transient changes in the BAEP when the lower pons and the 8th cranial nerve were retracted. Another patient had progressive increases in latency and decreases in amplitude and subsequent loss of the SEP cortical components during a period of intermittent temporary rostral basilar artery occlusion. Wave P13 was also lost during that period. The cortical components as well as Wave P13 returned after circulation was restored. The BAEPs were unchanged in the same patient during the period of temporary basilar artery occlusion. Fourteen patients had no significant abnormalities. There were no consistent changes during the various stages of operation. BAEP and SEP monitoring failed to identify ischemic events in 4 patients with neurological findings of brain stem ischemia immediately after operation (i.e., 25% false-negative studies).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗