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Biomedical subjects

L H Pitts

Publications and source records attributed to L H Pitts.

At least 91 records · Page 5Linked to original sources

Effect of hypoxia on traumatic brain injury in rats: Part 2. Changes in high energy phosphate metabolism.

The effect of different degrees of hypoxia on phosphate metabolism in the brains of impact-injured rats was studied using in vivo phosphorus-31 magnetic resonance (P-31 MR) spectroscopy. Sequential changes in P-31 MR spectra within 60 minutes of insult were compared among rats with hypoxia alone, impact injury alone, or a combined impact-hypoxic insult. Hypoxia alone (PaO2 of 40 mm Hg for 30 minutes) caused no remarkable changes in phosphorus spectra except a decrease in intracellular pH. In impact-injured rats, the concentration of inorganic phosphate (Pi) increased, but signals for phosphocreatine (PCr) and beta-adenosine triphosphate (beta-ATP) did not change, and the ratio of PCr/Pi changed only slightly to 7% below control value. When rats with a fluid percussion impact injury of 5 atm were subjected to hypoxic conditions of a PaO2 of 40 mm Hg for 15 minutes, the PCr/Pi ratio decreased by 14%, a value significantly below that of the impact alone group (P less than 0.05). After longer periods of hypoxia (PaO2 of 40 mm Hg for 30 minutes) in impact-injured rats, there were marked increases of Pi and significant decreases in signals for PCr and beta-ATP, which caused a marked decrease in the PCr/Pi ratio to 39% below control values (P less than 0.001). Milder hypoxia (PaO2 of 50 mm Hg for 30 minutes) plus impact injury caused smaller changes in high energy metabolite concentrations, and the PCr/Pi ratio decreased to 15% below control values.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

The therapeutic value of nimodipine in experimental focal cerebral ischemia. Neurological outcome and histopathological findings.

Recent studies suggest that nimodipine, a potent calcium-channel antagonist that causes significant cerebrovascular dilatation, may improve neurological outcome after acute experimental permanent focal cerebral ischemia when given before or immediately after occlusion of the middle cerebral artery (MCA) in various animals. The authors describe the effect of nimodipine on cerebral ischemia in a rat model. At 1, 4, or 6 hours after occlusion of the MCA, rats were treated in a double-blind technique with either nimodipine, placebo, or saline. Neurological and neuropathological evaluation was performed at 24 hours. Neurological outcome was better in rats treated with nimodipine 1, 4, or 6 hours after occlusion (p less than 0.001, p less than 0.01, p less than 0.05 respectively), and the size of areas of infarction was statistically smaller in nimodipine-treated groups (p less than 0.01, p less than 0.01, p less than 0.05, respectively) when compared with control rats treated with saline or placebo. The best neurological outcome and the smallest area of infarction were found in nimodipine-treated rats 1 hour after occlusion. Compared with controls, the size of the periphery of the infarcted area was smaller in nimodipine-treated rats. The results show that nimodipine improves neurological outcome and decreases the size of infarction when administered up to 6 hours after ischemic insult. These results suggest a possible mechanism of action of nimodipine on the "penumbra" of the ischemic area.

Animals↗

Neurotrauma care and the neurosurgeon: a statement from the Joint Section on Trauma of the AANS and CNS.

The AANS and CNS support the concept of organized neurosurgical trauma care consisting of the appropriate combination of prepared communities and institutions and of adequate numbers of committed neurosurgeons. Furthermore, we support the guidelines of the ACS regarding institutions designated to receive trauma patients, and support the concept of prehospital triage of trauma victims based upon well-trained EMS personnel guided by criteria selected by the local neurosurgical community. We support audit systems that include neurosurgeons to assess and improve the quality of neurotrauma care. By using the principles outlined above, neurosurgeons can plan, support, and evaluate whatever system their community or region requires for the optimal care of the neurotrauma patient.

Health Planning Guidelines↗

Efficacy of irradiation for incompletely excised acoustic neurilemomas.

The records of 124 patients treated for acoustic neurilemoma at the University of California, San Francisco, from 1945 through 1983 were reviewed. Patients were classified by the extent of surgical resection: total, nearly total (90% to 99% resection), subtotal (less than 90% resection), or biopsy. Thirty-one patients received irradiation as part of their primary treatment. Total resection of tumor, without irradiation, was associated with a 3% chance of local recurrence. One of 15 patients who had nearly total resection of their tumor and did not receive postoperative irradiation suffered a recurrence, compared with neither of the two patients who received postoperative irradiation (greater than 45 Gy) following nearly total resection. Postoperative irradiation (greater than 45 Gy) decreased the recurrence rate after subtotal resection from 46% (six of 13 cases without irradiation) to 6% (one of 17 cases: p = 0.01). All three patients treated by biopsy alone received postoperative irradiation (greater than 45 Gy), and none had a recurrence. Six patients were treated with preoperative irradiation because of excessive tumor vascularity; four are without evidence of disease 12 to 23 years later. Only three of seven patients treated with irradiation for tumor recurrence after surgical resection survived. It is concluded that postoperative irradiation significantly decreased the chance for local tumor progression following subtotal resection of acoustic neurilemoma, and that postoperative irradiation may be effective therapy following treatment by biopsy. Patients with total or nearly total resection appeared not to benefit from postoperative irradiation.

Adolescent↗

S-phase fraction of human brain tumors in situ measured by uptake of bromodeoxyuridine.

One hundred fifty-four patients with brain tumors of various types were given an intravenous infusion of the thymidine analogue bromodeoxyuridine (BUdR), 200 mg/m2, at the time of surgery but before biopsy of the tumor to label S-phase cells. Excised tumor specimens were fixed, sectioned, and stained by immunoperoxidase methods to detect BUdR. The labelling index (LI), or percentage of BUdR-labelled cells, was calculated for each tumor specimen. The LIs of glioblastomas, medulloblastomas, and most highly anaplastic astrocytomas were 5% to 20%. The majority of moderately anaplastic astrocytomas showed LIs of less than 1%, but 30% of them had LIs similar to those of highly malignant gliomas. Most pituitary adenomas and neurinomas showed LIs of less than 1%. Nonmalignant meningiomas had LIs of less than 1%, whereas malignant meningiomas had LIs higher than 2.7%. This is an important observation, because malignant meningiomas are not well-defined histopathologically and their growth rate and rate of recurrence cannot be predicted by current diagnostic procedures. By estimating the proliferative potential of individual tumors more precisely, the BUdR LI supplements histopathological diagnosis, allowing a more accurate estimate of prognosis and facilitating the design of treatment regimens for individual patients.

Adult↗

Traumatic intracerebral hematomas: timing of appearance and indications for operative removal.

Immediate and delayed traumatic intracerebral hematomas (ICH) can produce devastating secondary brain damage after severe head injury. The relationship between the initial injury and eventual occurrence, size, and time of appearance of such hematomas is not well understood, but has great importance since delayed appearance may necessitate delayed surgical decompression of developing lesions not present on early CT scans. We reviewed the records of 35 consecutive patients with operated post-traumatic ICH to document when these lesions appeared on CT, what were the indications for surgery, and what was eventual outcome. Time between injury and ICH appearance was categorized as immediate (0-3 hours), intermediate (3-6), delayed (6-24) or very delayed (later than 24 hours). ICH appearance was immediate in 20%, intermediate in 6%, delayed in 29%, and very delayed in 46%. Half of the patients were not comatose at the time of admission (GCS greater than or equal to 8). Hematoma removal was prompted by clinical deterioration or failure to improve in half the patients and by uncontrolled intracranial hypertension in the other half. Half the patients died, generally those in traumatic coma immediately after injury although advanced age also was associated with poor outcome. Only about one quarter of patients who require surgical removal of ICH can be shown to have their lesions soon after injury. Most operable intraparenchymal clots develop after initial CT scanning and trauma surgeons must be prepared to recognize and treat this delayed complication of brain injury. Even with aggressive management, ICH contribute significantly to poor outcome and improved treatment must be sought.

Adolescent↗

Is computed tomographic scanning necessary in patients with tentorial herniation? Results of immediate surgical exploration without computed tomography in 100 patients.

Computed tomographic (CT) scans are performed on virtually all patients with severe head injury at the time of admission. Because of the time involved in obtaining these studies, the evacuation of significant intracranial mass lesions is delayed. To avoid such delays, the authors performed burr-hole exploration for the diagnosis of intracranial hematomas before CT scans were obtained in 100 consecutive head-injured patients with clinical signs of tentorial herniation or upper brain stem dysfunction upon admission to the emergency room. Patients in whom a hematoma was discovered had a craniotomy for evacuation of the clot; those in whom the exploration was negative had a CT brain scan immediately after operation. Burr-hole exploration revealed extracerebral mass lesions in 56 patients. In 38 patients, the exploration was negative, and postoperative CT scanning showed no significant hematoma. Of 6 patients in whom the CT scan demonstrated extraaxial hematomas requiring surgical evacuation, 4 had subdural hematomas that were missed because the exploration was incomplete; 1 patient had an epidural hematoma and 1 had a subdural hematoma contralateral to a craniotomy on the side of a positive initial burr-hole exploration. Our results indicate that the relatively small subgroup of head-injured patients with early tentorial herniation or upper brain stem compression have a high incidence of immediate extraaxial hematomas and a low incidence of intracerebral hematomas. This is particularly true of patients over 30 years of age and those who suffer low speed trauma, such as falls and vehicle-pedestrian accidents.

Adult↗

Nuclear magnetic resonance imaging and spectroscopy in experimental brain edema in a rat model.

Many aspects of the use of high-resolution nuclear magnetic resonance (NMR) imaging in the examination of brain edema have not been fully explored. These include the quantitation of edema fluid, the ability to distinguish between various types of edema, and the extent to which tissue changes other than a change in water content can affect NMR relaxation times. The authors have compared NMR relaxation times obtained by both in vivo magnetic resonance imaging (MRI) and in vitro NMR spectroscopy of brain-tissue samples from young adult rats with cold lesions, fluid-percussion injury, hypoxic-ischemic injury, bacterial cerebritis, and cerebral tumor. Changes in relaxation times were compared with changes in brain water content, cerebral blood volume, and the results of histological examination. In general, both in vivo and in vitro longitudinal relaxation times (T1) and transverse relaxation times (T2) were prolonged in the injured hemispheres of all experimental groups. Water content of tissue from the injured hemispheres was increased in all groups. A linear correlation between T2 (but not T1) and water content was found. Changes in the values of T1 and T2 could be used to distinguish tumor from cold-injured tissue. Cerebral blood volume was reduced in the injured hemispheres and correlated inversely with prolongation of T1 and T2. The results of this study suggest that, in a clinical setting, prolongation of T2 is a better indicator of increased water content than prolongation of T1, yet quantitation of cerebral edema based solely upon prolongation of in vivo or in vitro T1 and T2 should be undertaken with caution.

Animals↗

A new microclip for vascular occlusion. Technical note.

A new microclip for use on blood vessels 300 mu to 1 mm in diameter is described. This clip is suitable for either temporary or permanent occlusion and has been used in experimental applications. Potential clinical applications are described.

Surgical Instruments↗

Combined magnetic resonance imaging and spectroscopy in experimental regional injury of the brain. Ischemia and impact trauma.

Combined magnetic resonance imaging (MRI) and spectroscopy (MRS) allows unique experimental insights into the central nervous system (CNS) disorders. Clinical applications are forthcoming. In order to address the potential clinical uses of MRI/MRS, experimentally induced focal brain lesions were evaluated with this modality. Focal lesions more closely mirror clinical situations than do global insults, but have rarely been the focus of MRS studies. Fluid-percussion trauma in 48 rats, focal ischemia in 18 rats and in 16 mongrel dogs were produced, with various degrees of severity. A discrepancy between temporal evolution data of MRI and MRS was found: MRI always showed an increase in lesion extension over time while 31P and 1H MRS almost always showed improvement. The severity and evolution of these MRS findings was surprising, and differed from the results reported for global brain injuries. Besides possibly reflecting real improvement in the metabolic state, other explanations for the phenomena exist. Diffusion of inorganic phosphate out of the regional site of injury and its reincorporation for more prominent lactate build-up in regional injury are possible. Therefore the use of MRS to predict metabolic and clinical outcomes of regional brain injury requires methodologic caution, but its combination to MRI offers an unprecedented tool for studies of focal CNS pathology.

Animals↗

Magnetic resonance imaging in the evaluation of nimodipine-treated acute experimental focal cerebral ischemia.

We evaluated the sensitivity of magnetic resonance (MR) imaging in documenting effects of nimodipine in experimental focal cerebral ischemia. Twenty-five Sprague Dawley rats underwent unilateral occlusion of the middle cerebral artery and were imaged at different intervals thereafter. Neuropathologic and neurologic data were correlated with MR imaging results. Compared with controls, nimodipine-treated rats showed a significantly smaller infarct size (p less than 0.001), as documented by MR imaging and confirmed by neuropathologic evaluations. A less intense signal on the T2 weighted sequence was found in nimodipine-treated rats in basal ganglia (p less than 0.001) and cortex (p less than 0.05). MR imaging may afford unprecedented diagnostic sensitivity in assessing pharmacologic efficacy in cerebral ischemia.

Animals↗

A novel double-surface coil approach to phosphorus-31 spectroscopy: a study of hemispheric brain injury in the rat.

An arrangement of two surface coils was devised to allow phosphorus-31 (31P) NMR spectroscopy of a localized hemispheric brain injury model in the rat. Two elliptical (8 X 12 mm) surface coils are placed parallel to each other (3 mm apart) over each side of the rat head. Spectra are collected from either the normal or the injured side of the head using the appropriate surface coil. A passive detuning method was used to eliminate unwanted coil-coil interactions. 31P imaging results with the two coils on phantoms show excellent isolation (6% signal overlap) between the two coils. The two-coil setup was then used to follow a time course of injury from the hemispheric injury model.

Adenosine Triphosphate↗

In vivo sodium-23 magnetic resonance surface coil imaging: observing experimental cerebral ischemia in the rat.

Sodium-23 magnetic resonance imaging can be used to detect and assess experimental cerebral ischemia in the rat. An imaging technique utilizing a surface coil is described to produce sodium magnetic resonance images of good quality and resolution within 10 min. A novel method of hemispheric occlusion showed edema in the right brain of the rat head within 3 hr after injury. The edema was especially pronounced by 12 hr with effects in the right brain, eye and surrounding muscle evident.

Animals↗

NMR imaging and spectroscopy of experimental brain edema.

A canine model of experimental brain edema utilizing the classic cold lesion technique was used to identify the optimal nuclear magnetic resonance (NMR) spin-echo imaging parameters needed to detect cerebral edema with maximum sensitivity. Each animal was studied with four separate spin-echo sequences, utilizing pulse intervals ranging from 0.5 to 2.0 seconds. The echo delays following each pulse interval were 28 and 56 msec. Cerebral edema was best identified with the longest pulse interval (2.0 seconds), and the second echo delay (56 msec). T1 and T2 relaxation values were obtained from in vitro spectroscopy. The relaxation times were prolonged in the edematous white matter; however, absolute T1 and T2 values proved of little use in comparing different animals.

Animals↗

Outcome from severe head injury in children and adolescents.

A consecutive series of 37 children (17 years old and under) with severe head injury is presented. The data confirm that morbidity and mortality are lower in children than in adults: 51% of these young patients had a good recovery or moderate disability at 6 months. The mortality rate in this series (33%) is higher than in some reports, but probably more closely approximates the death rate from these injuries in an unselected pediatric population than do statistics from tertiary care hospitals. There was no significant relationship between age and outcome in this age group, but mass lesions and uncontrolled intracranial hypertension adversely affected outcome. Diffuse cerebral swelling was commonly seen on computerized tomography scans, and generally was associated with a satisfactory outcome (75%). Two of 13 deaths were considered preventable, emphasizing the narrow therapeutic safety margin and extreme care required in treating these patients.

Adolescent↗

Computed tomographic evaluation of the optic canal in sudden traumatic blindness.

Using computed tomographic scans and reformatted images of the optic canal region, we were able to define osseous abnormalities in nine patients with sudden traumatic blindness resulting from indirect trauma to the optic nerve. Six patients had optic canal fractures, two had fractures of adjacent structures, and one patient did not have a fracture. Patients received corticosteroid therapy, surgical decompression of the optic canal, both types of treatment, or no specific treatment for the nerve injury. Although there was no correlation between the abnormality identified by computed tomography and treatment results, our findings provided further evidence that a canal fracture is not necessary for injury of the optic nerve to occur. We recommend that patients with sudden visual loss after blunt head trauma undergo a computed tomographic scan of the optic canal region.

Adolescent↗

Proton nuclear magnetic resonance spectroscopy of normal and edematous brain tissue in vitro: changes in relaxation during tissue storage.

Proton nuclear magnetic resonance relaxation times, T1 and T2, of water in unfixed gray and white matter from normal and edematous rabbit brain tissues were measured in vitro at 23 degrees C and 100 MHz to evaluate the effects of the temperature (-25 degrees C to 37 degrees C) and duration (0 to 96 h) of tissue storage on relaxation times. T1 and T2 tended to decrease during storage, probably from slow dehydration of the tissue. This effect was greatest in tissues stored at 37 degrees C and least in those stored at 4 and -25 degrees C; decreases in T1 and T2 were greater in white matter than in gray matter. Freezing brain tissue to -25 degrees C caused a sudden decrease in the T2 of normal white matter. Relaxation times were constant for 5 h in tissues stored at 23 degrees C and for 40 h at 4 degrees C. These results correlated well with corresponding tissue water loss.

Animals↗