Lawrence H. Pitts

Bio: Lawrence H. Pitts is an academic researcher from University of California, San Francisco. The author has contributed to research in topics: Acoustic neuroma & Head injury. The author has an hindex of 55, co-authored 146 publications receiving 11169 citations. Previous affiliations of Lawrence H. Pitts include Stanford University & University of California.

Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination.

Abstract: We have examined the incidence and size of infarction after occlusion of different portions of the rat middle cerebral artery (MCA) in order to define the reliability and predictability of this model of brain ischemia. We developed a neurologic examination and have correlated changes in neurologic status with the size and location of areas of infarction. The MCA was surgically occluded at different sites in six groups of normal rats. After 24 hr, rats were evaluated for the extent of neurologic deficits and graded as having severe, moderate, or no deficit using a new examination developed for this model. After rats were sacrificed the incidence of infarction was determined at histologic examination. In a subset of rats, the size of the area of infarction was measured as a percent of the area of a standard coronal section. Focal (1-2 mm) occlusion of the MCA at its origin, at the olfactory tract, or lateral to the inferior cerebral vein produced infarction in 13%, 67%, and 0% of rats, respectively (N = 38) and produced variable neurologic deficits. However, more extensive (3 or 6 mm) occlusion of the MCA beginning proximal to the olfactory tract--thus isolating lenticulostriate end-arteries from the proximal and distal supply--produced infarctions of uniform size, location, and with severe neurologic deficit (Grade 2) in 100% of rats (N = 17). Neurologic deficit correlated significantly with the size of the infarcted area (Grade 2, N = 17, 28 +/- 5% infarction; Grade 1, N = 5, 19 +/- 5%; Grade 0, N = 3, 10 +/- 2%; p less than 0.05). We have characterized precise anatomical sites of the MCA that when surgically occluded reliably produce uniform cerebral infarction in rats, and have developed a neurologic grading system that can be used to evaluate the effects of cerebral ischemia rapidly and accurately. The model will be useful for experimental assessment of new therapies for irreversible cerebral ischemia.

Evaluation of 2,3,5-triphenyltetrazolium chloride as a stain for detection and quantification of experimental cerebral infarction in rats.

Abstract: We have evaluated the use of 2,3,5-triphenyltetrazolium chloride (TTC) as an histopathologic stain for identification of infarcted rat brain tissue. The middle cerebral artery (MCA) of 35 normal adult rats was occluded surgically. At various times after surgical occlusion, rats were sacrificed and brain slices were obtained and stained with TTC or hematoxolin and eosin (H & E); the size of the area of infarcted tissue stained by each method was quantified. In rats sacrificed 24 hr after occlusion of the MCA, the size of the area of infarction was 21 +/- 2% of the coronal section for TTC, and 21 +/- 2% for H & E (mean +/- S.D., N = 13). The size of areas of infarction determined by either staining method was not significantly different in area by the paired test, and a significant correlation between sizes determined by each method was found by linear regression analysis (r = 0.91, slope = 0.89, and the y intercept = 4.4%). Staining with TTC is a rapid, convenient, inexpensive, and reliable method for the detection and quantification of cerebral infarction in rats 24 hr after the onset of ischemia.

Hypotension, hypoxia, and head injury: frequency, duration, and consequences.

Abstract: Background Retrospective studies have suggested an association between systemic hypotension and hypoxia and worsened outcome from traumatic brain injury. Little is known, however, about the frequency and duration of these potentially preventable causes of secondary brain injury. Hypothesis Early episodes of hypoxia and hypotension occurring during initial resuscitation will have a significant impact on outcome following traumatic brain injury. Design Prospective cohort study. Setting Urban level I trauma center. Patients Patients with a traumatic brain injury who had a Glasgow Coma Score of 12 or less within the first 24 hours of admission to the hospital and computed tomographic scan results demonstrating intracranial pathologic features. Patients who died in the emergency department were excluded from the study. Main Outcome Measures Automated blood pressure and pulse oximetry readings were collected prospectively from the time of arrival through initial resuscitation. The number and duration of hypotensive (systolic blood pressure, ≤90 mm Hg) and hypoxic (oxygen saturation, ≤92%) events were analyzed for their association with mortality and neurological outcome. Results One hundred seven patients met the enrollment criteria (median Glasgow Coma Score, 7). Overall mortality was 43%. Twenty-six patients (24%) had hypotension while in the emergency department, with an average of 1.5 episodes per patient (mean duration, 9.1 minutes). Of these 26 patients with hypotension, 17 (65%) died ( P = .01). When the number of hypotensive episodes increased from 1 to 2 or more, the odds ratio for death increased from 2.1 to 8.1. Forty-one patients (38%) had hypoxia, with an average of 2.1 episodes per patient (mean duration, 8.7 minutes). Of these 41 patients with hypoxia, 18 (44%) died ( P = .68). Conclusions Hypotension, but not hypoxia, occurring in the initial phase of resuscitation is significantly ( P = .009) associated with increased mortality following brain injury, even when episodes are relatively short. These prospective data reinforce the need for early continuous monitoring and improved treatment of hypotension in brain-injured patients.

Decreased mortality from brain abscesses since advent of computerized tomography.

Abstract: ✓ No deaths have occurred among 20 consecutive patients with intraparenchymal brain abscesses treated at the University of California, San Francisco, since computerized tomographic (CT) brain scanning became a routine diagnostic procedure (study period: July, 1974, to June, 1977). These patients have been compared to 18 consecutive cases treated without benefit of CT analysis (January, 1970, to June, 1974) in order to determine the factors responsible for the recently improved prognosis. The mortality rate was 44% for all cases and 36% for all operated patients treated before the availability of CT. Similar morbidity (about 33%) was seen in survivors from both series. No significant differences in the two groups were noted with respect to patient population and antibiotic or corticosteroid therapy. Among the factors that may have contributed to the improved results for patients diagnosed with CT are: less frequent occurrence of multiple abscesses, fewer patients with poor preoperative clinical status, and...

Outcome from severe head injury in children and adolescents

Abstract: 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.

Reversible middle cerebral artery occlusion without craniectomy in rats.

Abstract: To develop a simple, relatively noninvasive small-animal model of reversible regional cerebral ischemia, we tested various methods of inducing infarction in the territory of the right middle cerebral artery (MCA) by extracranial vascular occlusion in rats. In preliminary studies, 60 rats were anesthetized with ketamine and different combinations of vessels were occluded; blood pressure and arterial blood gases were monitored. Neurologic deficit, mortality rate, gross pathology, and in some instances, electroencephalogram and histochemical staining results were evaluated in all surviving rats. The principal procedure consisted of introducing a 4-0 nylon intraluminal suture into the cervical internal carotid artery (ICA) and advancing it intracranially to block blood flow into the MCA; collateral blood flow was reduced by interrupting all branches of the external carotid artery (ECA) and all extracranial branches of the ICA. In some groups of rats, bilateral vertebral or contralateral carotid artery occlusion was also performed. India ink perfusion studies in 20 rats documented blockage of MCA blood flow in 14 rats subjected to permanent occlusion and the restoration of blood flow to the MCA territory in six rats after withdrawal of the suture from the ICA. The best method of MCA occlusion was then selected for further confirmatory studies, including histologic examination, in five additional groups of rats anesthetized with halothane. Seven of eight rats that underwent permanent occlusion of the MCA had resolving moderately severe neurologic deficits (Grade 2 of 4) and unilateral infarcts averaging 37.6 +/- 5.5% of the coronal sectional area at 72 hours after the onset of occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

A novel MHC class I–like gene is mutated in patients with hereditary haemochromatosis

Abstract: Hereditary haemochromatosis (HH), which affects some 1 in 400 and has an estimated carrier frequency of 1 in 10 individuals of Northern European descent, results in multi-organ dysfunction caused by increased iron deposition, and is treatable if detected early. Using linkage-disequilibrium and full haplotype analysis, we have identified a 250-kilobase region more than 3 megabases telomeric of the major histocompatibility complex (MHC) that is identical-by-descent in 85% of patient chromosomes. Within this region, we have identified a gene related to the MHC class I family, termed HLA-H, containing two missense alterations. One of these is predicted to inactivate this class of proteins and was found homozygous in 83% of 178 patients. A role of this gene in haemochromatosis is supported by the frequency and nature of the major mutation and prior studies implicating MHC class I-like proteins in iron metabolism.

Ischemic Cell Death in Brain Neurons

Abstract: This review is directed at understanding how neuronal death occurs in two distinct insults, global ischemia and focal ischemia. These are the two principal rodent models for human disease. Cell dea...