Biomedical subjects

J T Hoff

Publications and source records attributed to J T Hoff.

At least 55 records · Page 3Linked to original sources

PubMed1999

Effect of intracerebral and subdural hematomas on energy-dependent transport across the blood-brain barrier.

Although both intracerebral and subdural hematomas induce brain edema, previous studies have indicated that they may have different cerebrovascular effects. Our own investigations have demonstrated that while subdural hematomas (SDH) are associated with ischemia this is not the case following intracerebral hematomas (ICH). Previous studies have demonstrated a decrease in energy-dependent transport of glutamine across the blood-brain barrier (BBB) following focal cerebral ischemia. The present study investigates this further by examining the effects of SDH, ICH, and intracerebral thrombin injections, an agent involved in ICH-induced injury, on blood to brain glutamine transport. The injection of 200 microL of blood into the subdural space induced a marked reduction in glutamine transport (Ki, influx rate constant) into the cerebral cortex at 4 and 24 h following SDH (sham, 105+/-4% of contralateral cortex; SDH 4 h, 63+/-5%, p<0.01; SDH 24 h, 47+/-12%, p<0.05). There were no significant changes in glutamine Ki in subcortical areas following SDH. Following ICH (200-microL clot); however, there were only modest decreases in glutamine Ki in subcortical areas (sham, 98+/-2% of right cortex; ICH 4 h, 91+/-5%, p<0.01; ICH 24 h, 91+/-2%, p<0.05). Intracerebral injection of thrombin (5U) had minimal effect on glutamine Ki, in subcortical areas, at 4 h and induced a modest decrease in transport at 24 h (sham, 98+/-2% of right cortex; thrombin 4 h, 98+/-2%; thrombin 24 h, 86+/-2%, p<0.05). The present studies demonstrate marked differences in the effects of ICH and SDH on BBB function.

Animals↗

PubMed1999

Use of factor IX complex in warfarin-related intracranial hemorrhage.

OBJECTIVE: Anticoagulation-treated patients presenting with intracranial hemorrhage, including subdural hematoma, epidural hematoma, subarachnoid hemorrhage, and intracerebral hemorrhage, require urgent correction of their coagulopathy to prevent worsening hemorrhage and to facilitate surgical intervention when necessary. In this study, we compared the use of fresh frozen plasma (FFP) with that of Factor IX complex concentrate (FIXCC) to achieve rapid correction of warfarin anticoagulation. METHODS: Patients admitted to a tertiary care center with computed tomography-proven intracranial hemorrhage and a prothrombin time of more than 17 seconds were considered for inclusion in the study protocol. Complete data sets were obtained for eight patients randomized to treatment with FFP and five patients randomized to treatment with FFP supplemented with FIXCC. The prothrombin time and International Normalized Ratio were measured every 2 hours for 14 hours. Correction of anticoagulation was defined as an International Normalized Ratio of < or =1.3. RESULTS: A difference in repeated International Normalized Ratio measurements during the first 6 hours of correction was observed between the FIXCC and FFP groups (P < 0.03). The rate of correction was greater (P < 0.01) and the time to correction was shorter (P < 0.01) for the FIXCC-treated group. No difference in neurological outcomes was detected between groups, but a higher complication rate was observed for the FFP-treated group. CONCLUSION: The use of FIXCC accelerated correction of warfarin-related anticoagulation in the presence of intracranial hemorrhage.

Factor IX↗

PubMed1999

Attenuation of thrombin-induced brain edema by cerebral thrombin preconditioning.

BACKGROUND AND PURPOSE: Edema formation after intracerebral hemorrhage has been linked to thrombin toxicity induced by the clot. However, thrombin at low concentrations actually protects neurons and astrocytes in culture from hypoglycemic and ischemic cell death. It is also known that a brief episode of brain ischemia increases neuronal tolerance to a subsequent severe ischemic episode. The objective of this study was to investigate whether pretreatment of the brain with low-dose thrombin induces tolerance to a subsequent large dose of thrombin injected into brain parenchyma. METHODS: The rat brain was preconditioned with 1 U thrombin by direct infusion into the right caudate nucleus. After thrombin pretreatment, the effects of a large dose (5 U) of thrombin on brain edema formation were studied at different intervals. We examined whether heat-shock protein (HSP) 27, HSP32, and HSP70 were induced by Western blot analysis, immunocytochemistry, and immunofluorescent double staining. RESULTS: Thrombin pretreatment significantly attenuated the brain edema that normally follows the infusion of a large dose of thrombin (79.2+/-0.4 versus 84.0+/-0.3; P<0.01). This effect was abolished by the thrombin inhibitor hirudin. Time course studies showed that the maximal effect of thrombin preconditioning (TPC) on brain edema formation was 7 days after pretreatment. This time course corresponded to marked upregulation of HSP27 in the ipsilateral brain. TPC also induced HSP32, but this effect occurred earlier than the effect on edema formation. TPC had no effect on HSP70. Immunocytochemistry and immunofluorescent double labeling showed that HSP27 and HSP32 were expressed in astrocytes after TPC. CONCLUSIONS: OFF phenomenon of thrombin-induced tolerance of the brain to edema formation may be related to HSP27 induction.

Animals↗

PubMed1999

Adenoviral nerve growth factor and beta-galactosidase transfer to spinal cord: a behavioral and histological analysis.

OBJECT: The present study characterizes the time course and loci of gene expression induced by the administration of adenoviral vectors into spinal cord. Although a marked inflammatory response to these vectors occurred, no effect on spinal cord function was seen in the 1st postoperative week. The expression of transgenic genes delivered by viral vectors is being exploited throughout the nervous system. The present study utilized adenoviral vectors containing the Rous sarcoma virus (RSV) promoter and a nuclear localization signal to achieve transgenic expression in mammalian spinal cord. METHODS: Initial experiments utilizing the vector Ad.RSVlacZ (10(12) particles/ml) injected into the region of the central canal resulted in viral gene expression stretching over approximately 1.2 cm of spinal cord. Gene expression was first detected 3 days following viral administration and lasted until postinjection Day 14 with peak expression at Day 7. A variety of cell types in both white and gray matter expressed lacZ. Transgenic expression of the neurotrophin nerve growth factor (NGF) was achieved using injections of Ad.RSVNGF. On histological examination mononuclear inflammatory infiltrate and gliosis were revealed surrounding the injection sites of spinal cords receiving adenovirus but not vehicle. To assess spinal cord function during viral gene expression, animals previously trained in an operant runway task were tested at 7 days postinjection (the peak of viral gene expression) and demonstrated no changes in spinal cord function. CONCLUSIONS: Results of this study using adenoviral neurotrophic gene transfer indicate that it provided an effective tool for the delivery of potentially therapeutic proteins to the injured or diseased spinal cord.

Adenoviridae↗

PubMed1998

Role of blood clot formation on early edema development after experimental intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Blood "toxicity" is hypothesized to induce edema and brain tissue injury following intracerebral hemorrhage (ICH). Lobar ICH in pigs produces rapidly developing, marked perihematomal edema (>10% increase in water content) associated with clot-derived plasma protein accumulation. Coagulation cascade activation and, specifically, thrombin itself contribute to edema development during the first 24 hours after gray matter ICH in rats. In the present study, we sought to determine whether blood clot formation is necessary for edema development by comparing intracerebral infusions of heparinized and unheparinized blood in pig (white matter) and in rat (gray matter). We also examined heparin's effect on thrombin-induced gray matter edema. METHODS: In pigs, we infused autologous blood (with or without heparin) into the cerebral white matter to produce lobar hematomas and froze the brains in situ at 1, 4, or 24 hours after ICH. We determined hematomal and perihematomal edema volumes on coronal sections by computer-assisted morphometry. In rats, we infused either blood or thrombin (with or without heparin) into the basal ganglia and measured water, sodium, and potassium contents at 24 hours after ICH. RESULTS: In pigs, unheparinized blood induced rapid (at 1 hour) and prolonged (24 hours) perihematomal edema (average volume, 1.29+/-0. 20 mL; n=6). No perihematomal edema was present following heparinized blood infusions (n=6). In rats, unheparinized blood produced significantly greater edema than heparinized blood infusions. As with whole blood, thrombin-induced gray matter edema at 24 hours was significantly reduced by coinjection of heparin. CONCLUSIONS: After ICH, blood clot formation is required for rapid and prolonged edema development in perihematomal white and gray matter. Thrombin also contributes to prolonged edema in gray matter.

Animals↗

PubMed1998

Plasminogen activators potentiate thrombin-induced brain injury.

BACKGROUND AND PURPOSE: Evidence suggests that cerebral edema following intracerebral hemorrhage (i.c.h.) results from a mass effect in combination with neurotoxic injury from clot-derived substrates such as thrombin. Thrombolytics can compete for thrombin inhibitors endogenous to the brain. This study examines the effect of intracerebral infusion of thrombolytics, tissue plasminogen activator (tPA), and urokinase (uPA), individually and in combination with thrombin. METHODS: Various 100 microL solutions were stereotactically infused into the right basal ganglia of adult male rats. Animals were euthanized 24 hours later, and brain sections were taken for measurement of water, sodium, and potassium content. RESULTS: Regardless of dose, when infused independently tPA (2 micrograms) and uPA (2000 and 5000 Plough units) failed to produce any significant tissue edema compared with vehicle control tissues. However, when either thrombolytic was infused concomitantly with thrombin (1 or 5 U), brain water, sodium, and potassium content all demonstrated a potentiation of thrombin-induced brain injury (P < 0.05). In addition, animal deaths were significantly greater than expected in animals receiving a combination of tPA (2 micrograms) and thrombin (5 U) compared with either drug alone (P < 0.001). CONCLUSIONS: This study indicates that brain edema caused by thrombin can be greatly amplified by the presence of plasminogen activators, perhaps because the latter compete for naturally occurring thrombin inhibitors. In the context of ICH, our results suggest that the use of tPA or uPA to lyse clotted blood in brain parenchyma may promote edema formation in surrounding tissue.

Animals↗

PubMed1998

Magnetic resonance evaluation of ventrolateral medullary compression in essential hypertension.

OBJECT: The authors designed a blinded prospective study comparing patients with essential hypertension to patients without hypertension in which magnetic resonance (MR) imaging was used to evaluate the role of lateral medullary compression by adjacent vascular structures as a cause of neurogenic hypertension. METHODS: Patients with documented essential hypertension were recruited to undergo thin-slice axial brainstem MR imaging evaluation. Nonhypertensive (control) patients scheduled to undergo MR imaging for other reasons also underwent thin-slice MR imaging to form a basis for comparison. Magnetic resonance images obtained in patients from the hypertensive (30 patients) and the control (45 patients) groups were then compared by four independent reviewers (two neuroradiologists and two neurosurgeons) who were blinded to the patients' diagnosis and hypertensive status. Images were reviewed with regard to left versus right vertebral artery (VA) dominance, compression of the medulla on the left and/or right side, and brainstem rotation. Medullary compression was graded as either vessel contact without associated brainstem deformity or vessel contact with associated brainstem deformity. CONCLUSIONS: There was a tendency toward left VA dominance in the hypertensive group compared with the control group, although a significant difference was shown by only one of the four reviewers. There were no differences in brainstem compression or rotation between the hypertensive and nonhypertensive groups. These results are contrary to those of recently published studies in which MR imaging and/or MR angiography revealed lateral brainstem vascular compression in hypertensive patients but not in nonhypertensive (control) patients. Reasons for this discrepancy are discussed. On the basis of their own experience and that of others, the authors believe that neurogenic hypertension does exist. However, thin-slice MR imaging may not be a reliable method for detecting neurovascularly induced essential hypertension and the prevalence of neurovascular compression as the source of hypertension may be overestimated when using current imaging techniques.

Adolescent↗

PubMed1998

Sequential outer table craniotomy a in hyperossified meningioma. Technical note.

A hyperossified meningioma with significant calvarial thickening is fairly common. Craniectomy of the involved region followed by cranioplasty is usually required to resect the bone overgrowth. However, in some cases, the hyperossified calvaria is too thick to allow safe penetration with a craniotome or trephine. In this report, the authors present a technique for preserving the outer calvaria while still resecting the majority of the underlying tumor mass. The key is to perform a craniotomy in a region adjacent to the hyperossified bone and to remove the tumorous, ossified inner table through this "window" by means of a high-speed drill. A second craniotomy can then be performed over the undermined area; this maneuver can be advanced and repeated until the tumor is resected. Frameless stereotactic guidance and microplates are useful in performing this procedure.

Craniotomy↗

PubMed1998

Correlation of intraluminal thrombosis in brain tumor vessels with postoperative thrombotic complications: a preliminary report.

OBJECT: Thrombotic complications (deep vein thrombosis and/or pulmonary embolization [DVT/PE]) occur in 18 to 50% of patients harboring brain tumors who undergo neurosurgical procedures. Such patients are at risk for DVT/PE because of immobility, paresis, hypovolemia, and lengthy surgery. The present study was undertaken to see whether tumor patients at highest risk for DVT/PE could be identified so that augmentation of prophylactic measures might be used to reduce the incidence of thrombotic complications. METHODS: The authors conducted a retrospective analysis of 488 patients enrolled in their brain tumor registries between 1988 and 1995, identifying 57 patients (12%) with recorded symptomatic DVT, PE, or both postoperatively. In 24 of these 57 cases histological specimens were retrievable for review, allowing an in-depth analysis. Forty-five patients were lost to follow-up review, and the remaining 386 patients had no record of systemic thrombosis. Slides of pathological specimens were retrievable in 50 cases in which there was no DVT/PE. From these 50 cases, 25 were selected at random to represent the control group by a blinded observer. Seventeen (71%) of the 24 brain tumor specimens obtained in patients with DVT/PE stained positively for intraluminal thrombosis (ILT) after hematoxylin and eosin had been applied. The odds ratio associated with the presence of ILT was 17.8, with a confidence interval ranging from 4 to 79.3. No evidence of ILT was found in 22 patients (88%) within the control group (p < 0.0001, Fisher's exact test). Other factors that may predispose patients with brain tumors to DVT/PE-limb paresis, extent of tumor removal, and duration of the surgery-were also analyzed and found not to be statistically significant. Therefore, these factors were not the basis for differences seen between the study and control groups. CONCLUSIONS: These preliminary observations suggest that the presence of ILT within malignant glioma or glioblastoma tumor vessels may represent a marker of tumor-induced hypercoagulability.

Adult↗

PubMed1998

Erythrocytes and delayed brain edema formation following intracerebral hemorrhage in rats.

OBJECT: The mechanisms of brain edema formation following spontaneous intracerebral hemorrhage (ICH) are not well understood. In previous studies, no significant edema formation has been found 24 hours after infusion of packed red blood cells (RBCs) into the brain of a rat or pig; however, there is evidence that hemoglobin can be neurotoxic. In this study, the authors reexamined the role of RBCs and hemoglobin in edema formation after ICH. METHODS: The experiments involved infusion of whole blood, packed RBCs, lysed RBCs, rat hemoglobin, or thrombin into the right basal ganglia of Sprague-Dawley rats. The animals were killed at different time points and brain water and ion contents were measured. The results showed that lysed autologous erythrocytes, but not packed erythrocytes, produced marked brain edema 24 hours after infusion and that this edema formation could be mimicked by hemoglobin infusion. Although infusion of packed RBCs did not produce dramatic brain edema during the first 2 days, it did induce a marked increase in brain water content 3 days postinfusion. Edema formation following thrombin infusion peaked at 24 to 48 hours. This is earlier than the peak in edema formation that follows ICH, suggesting that there is a delayed, nonthrombin-mediated, edemogenic component of ICH. CONCLUSIONS: These results demonstrate that RBCs play a potentially important role in delayed edema development after ICH and that RBC lysis and hemoglobin toxicity may be useful targets for therapeutic intervention.

Animals↗

PubMed1997

Assessment of training progress and examinations.

Board certification and accreditation of training programs began as measures of quality in the United States. Both functions were done initially by the American Board of Neurological Surgery (ABNS). In 1954, certification of trainees and accreditation of programs became separate functions in order to eliminate potential conflicts of interest. Currently, the ABNS certifies trainees who have completed neurological surgery training in an accredited program whose curriculum includes operative and nonoperative experience, have the endorsement of the training program director, and have passed the written in-training examinations and a final oral examination. Accreditation of training programs is a separate function administered by the Residency Review Committee (RRC) of the Accreditation Council for Graduate Medical Education. Individual programs are reviewed on a periodic basis for quality of the curriculum, facilities, faculty, and patient volume. The ABNS and the RRC are separate groups, both comprised of neurosurgeons with a strong commitment to the educational process.

Accreditation↗

PubMed1997

Mechanisms of edema formation after intracerebral hemorrhage: effects of thrombin on cerebral blood flow, blood-brain barrier permeability, and cell survival in a rat model.

Recently, the authors showed that thrombin contributes to the formation of brain edema following intracerebral hemorrhage. The current study examines whether the action of thrombin is due to an effect on cerebral blood flow (CBF), vasoreactivity, blood-brain barrier (BBB) function, or cell viability. In vivo solutions of thrombin were infused stereotactically into the right basal ganglia of rats. The animals were sacrificed 24 hours later; CBF and BBB permeability were measured. The actions of thrombin on vasoreactivity were examined in vitro by superfusing thrombin on cortical brain slices while monitoring microvessel diameter with videomicroscopy. In separate experiments C6 glioma cells were exposed to various concentrations of thrombin, and lactate dehydrogenase release, a marker of cell death, was measured. The results indicate that thrombin induces BBB disruption as well as death of parenchymal cells, whereas CBF and vasoreactivity are not altered. The authors conclude that cell toxicity and BBB disruption by thrombin are triggering mechanisms for the edema formation that follows intracerebral hemorrhage.

Animals↗

PubMed1997

Seizures induced by intracerebral injection of thrombin: a model of intracerebral hemorrhage.

The coagulation cascade plays an important role in brain edema formation caused by intracerebral blood. In particular, thrombin produces brain injury via direct brain cell toxicity. Seizures and increased cerebral electrical activity are commonly associated with intracerebral blood and are possible effects of thrombin leading to cell injury in the brain. In this study, artificial clots containing concentrations of thrombin found in hematomas were infused intracerebrally in rats. The animals were observed clinically for seizure activity, behavior, and neurological deficits. Several animals underwent video electroencephalographic (EEG) monitoring during intracerebral infusion and for 30 minutes postinfusion. All animals were killed 24 hours after injection, and brain water and ion contents were measured to determine the amount of brain edema. Clinically, thrombin produced focal motor seizures in all animals. None of the control animals or those receiving N[alpha]-(2-Naphthalenesulfonyl-glycyl)-4-amidino-DL-phenylalanine -piperidide (alpha-NAPAP), a thrombin inhibitor added to the thrombin, showed clinical evidence of seizures. Of the rats undergoing EEG monitoring, all animals receiving thrombin showed electrical evidence of seizure activity, whereas none of the control animals exhibited seizure activity. There was no evidence of seizure activity on EEG monitoring when alpha-NAPAP was injected along with the thrombin. In addition, the artificial clots containing thrombin produced agitation and a circling tendency in the rats, along with brain edema. These results indicate that the coagulation cascade is involved in seizure production and increased brain electrical activity, which contribute to the neurological deficits and brain edema formation that are seen with intracerebral hemorrhage.

Animals↗

PubMed1996

The role of the coagulation cascade in brain edema formation after intracerebral hemorrhage.

The coagulation cascade has a potential role in brain edema formation due to intracerebral hemorrhage. In this study blood and other solutions were injected stereotactically into the right basal ganglia in rats. Twenty-four hours following injection, brain water and ion contents were measured to determine the amount of brain edema. Intracerebral blood resulted in an increase in brain water content. The amount of brain edema surrounding the intracerebral hematoma was reduced by a thrombin inhibitor N alpha-(2-Naphthalenesulfonylglycyl)-4-amidino-DL-phenylalaninep iperidide, (alpha-NAPAP) infused into the hematoma after the clot had been allowed to solidify. The inhibitor did not alter the actual size of the clot mass. An artificial clot composed of fibrinogen, thrombin, and styrene microspheres also produced brain edema. A fibrin clot led to edema formation even in the absence of mass effect provided by the microspheres. The single component responsible for production of brain edema in all these models was thrombin. The edema was formed in response to a fibrinogen-independent pathway. These results indicate that the coagulation cascade is involved in brain edema that develops adjacent to an intracerebral hematoma.

Animals↗

PubMed1996

Edema from intracerebral hemorrhage: the role of thrombin.

The mechanism by which intracerebral hemorrhage leads to the formation of brain edema is unknown. This study assesses the components of blood to determine if any are toxic to surrounding brain. Various solutions were infused stereotactically into the right basal ganglia of rats. The animals were sacrificed 24 hours later; brain edema and ion contents were measured. Whole blood caused an increase in brain water content and ion changes consistent with brain edema. Concentrated blood cells, serum from clotted blood, and plasma from unclotted blood all failed to provoke edema formation when infused directly into the brain. On the other hand, activation of the coagulation cascade by adding prothrombinase to plasma did produce brain edema. The edema response to whole blood could be prevented by adding a specific thrombin inhibitor, hirudin, to the injected blood. This study indicates that thrombin plays an important role in edema formation from an intracerebral blood clot.

Animals↗

PubMed1996

Thrombin-soaked gelatin sponge and brain edema in rats.

Previous work from this laboratory has shown that injection of thrombin into rat basal ganglia causes brain edema. This study investigates the effect on rat brain of thrombin-soaked gelatin sponge (used for intraoperative hemostasis in clinical situations) at a concentration similar to that used in humans. Three models were developed to evaluate this effect. In the first model, a gelatin sponge soaked with vehicle or thrombin (100 U/cm3) was placed on the intact pia of the right frontal lobe in rats without cortical lesions. In the second model, frontal cortex was excised (3 mm3) and the exposed brain was cauterized with electrocoagulation. Gelatin sponge was soaked with vehicle or thrombin (1000, 100, 10, or 1 U/cm3) and placed in the lesion site. In the third model, hirudin, a specific thrombin antagonist, was added to the thrombin-soaked gelatin sponge and placed in a similar cortical lesion to determine if the observed effects were specific to thrombin. The dose-response range for thrombin was determined qualitatively by magnetic resonance (MR) imaging and quantitatively by brain edema formation 24 hours after exposure. We found no edema in the cortically intact rats. The rats given cortical lesions developed significant edema when subjected to 1000, 100, and 10 U/cm3 thrombin as seen on MR imaging and at 100 and 10 U/cm3 thrombin as revealed by wet/dry weight and ion studies of brain tissue. Topical hirudin prevented thrombin-induced edema. It is concluded that thrombin-soaked gelatin sponges cause or enhance significant brain edema in rats at concentrations typically used for human neurosurgery.

Administration, Topical↗

PubMed1995

Continuous midazolam/atracurium infusions for the management of increased intracranial pressure.

Maintaining the pressure/volume balance in the brain is a challenging goal for the neuroscience team caring for patients with traumatic brain insults. Often, standard therapies are not effective in controlling increased intracranial pressure (ICP). Four severe traumatic brain injury patients given continuous infusions of midazolam and atracurium showed control of otherwise unstable ICPs. Midazolam and atracurium infusions are now considered an acceptable form of therapeutic intervention for our patients requiring such treatment. Intensive nursing care considerations for patients using the combined pharmacologic therapy are essential.

Adult↗

PubMed1995

Neurosurgery at the University of Michigan.

Neurosurgery at the University of Michigan was established as a specialty three-quarters of a century ago by Max Minor Peet. It developed under the successive leadership of Edgar Allan Kahn, Richard Coy Schneider, and Julian T. Hoff. Each has made unique contributions to the program, which has a strong tradition of teaching, research, and patient care. This article traces the development of the training program in neurosurgery at Michigan, focusing on its historical background, past accomplishments, present structure, and future directions.

Curriculum↗