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Julian T Hoff

Publications and source records attributed to Julian T Hoff.

At least 19 recordsLinked to original sources
PubMed2006

Predictors of pain and function in persons with spinal stenosis, low back pain, and no back pain.

STUDY DESIGN: Longitudinal masked, double-controlled cohort study. OBJECTIVES: To determine prognosis and predictors of function and pain in persons with spinal stenosis. SUMMARY OF BACKGROUND DATA: The clinical syndrome of spinal stenosis is common and disabling, but not clearly related to anatomic measures. Prognosis not well studied. METHODS: Persons 55 to 80 years of age with and without stenosis on preliminary review of magnetic resonance imaging (MRI), and asymptomatic volunteers underwent screening, questionnaires, physical examination, ambulation testing, masked electromyogram (EMG), and masked MRI scans; these were repeated at >18 months. RESULTS: Twenty-three asymptomatic, 28 back pain, and 32 clinically diagnosed stenosis subjects underwent follow-up. Although initial and follow-up diagnosis tended to agree (kappa = 0.394, P < 001), there were substantial shifts between the three groups. Among persons with clinically diagnosed stenosis, every measure trended for improvement, including significant changes in pain, ambulation, and EMG. Ambulation velocity and Pain Disability Index at follow-up were predicted by initial disability measures. Pain was predicted by initial sleep difficulty but not initial pain. EMG and MRI did not predict function or pain. CONCLUSION: Clinically recognized spinal stenosis is fluctuating and largely improving, and in continuum with back pain and no symptoms. Since anatomic and neurologic deficits do not predict future function, they should not be weighed heavily in surgical risk-benefit discussions.

Aged↗
PubMed2006

The role of complement C3 in intracerebral hemorrhage-induced brain injury.

Activation of the complement cascade contributes to brain injury after intracerebral hemorrhage (ICH). However, a recent study found that complement C5 deficient mice had enhanced ICH-induced brain injury. The present study, therefore, investigated the role of complement C3 (which is upstream from C5) in ICH. Male complement C3 deficient and sufficient mice had an intracerebral infusion of 30-muL autologous whole blood. The mice were killed and the brains were sampled for edema, Western blotting, immunohistochemistry and histologic analysis. Behavioral tests including forelimb use asymmetry test and corner turn were also performed before and after ICH. Compared to complement C3 sufficient mice, C3 deficient mice had less brain edema, lower hemeoxygenase-1 levels, less microglia activation and neutrophil infiltration around the clot after ICH. In addition, the C3-deficient mice had less ICH-induced forelimb use asymmetry deficits compared with C3-sufficient mice. These results suggest complement activation may affect heme metabolism and the inflammatory response after ICH suggesting that complement C3 is an important factor causing ICH-induced brain injury.

Animals↗
PubMed2006

Spinal stenosis, back pain, or no symptoms at all? A masked study comparing radiologic and electrodiagnostic diagnoses to the clinical impression.

OBJECTIVE: To assess the relations between clinically recognized lumbar spinal stenosis and the conclusions of masked radiologists and electrodiagnosticians. DESIGN: Prospective, masked, double-controlled trial. SETTING: University spine center. PARTICIPANTS: One hundred fifty persons age 55 to 80 years with or without back pain and with or without magnetic resonance imaging (MRI)-demonstrated stenosis, screened for neuropathy risk, previous surgery, or cancer. INTERVENTIONS: Questionnaires on pain and function; ambulation testing and physical examination; and masked electrodiagnotics and MRI. MAIN OUTCOME MEASURE: Diagnostic impressions of the examining clinician, radiologist, and electrodiagnostician. RESULTS: Following application of post hoc exclusion criteria and elimination of patients due to incomplete or inadequate test data, the clinical diagnosis was lumbar stenosis in 50 subjects, back pain in 44 subjects, and no pain in 32 subjects. Radiologic and clinical impression had no relation (P = .80 vs asymptomatic, P = .99 vs back pain controls). Electrodiagnostic impression trended to relate to clinical impression (P = .14 vs asymptomatic, P = .09 vs back pain). Retrospective application of age-related electrodiagnostic norms for paraspinal electromyographic and limb motor unit changes, established in this study, reclassified 13 of the 17 asymptomatic persons whom the electrodiagnostician thought had stenosis. The clinical impression did correspond to history and physical examination findings typically associated with spinal stenosis and to the independent impression of a neurosurgeon who examined MRI and clinical, but not to the electrodiagnostic data. CONCLUSIONS: The impression obtained from an MRI scan does not determine whether lumbar stenosis is a cause of pain. Electrodiagnostic consultation may be useful, especially if age-related norms obtained in this study are applied.

Activities of Daily Living↗
PubMed2006

Mechanisms of brain injury after intracerebral haemorrhage.

The past decade has resulted in a rapid increase in knowledge of mechanisms underlying brain injury induced by intracerebral haemorrhage (ICH). Animal studies have suggested roles for clot-derived factors and the initial physical trauma and mass effect as a result of haemorrhage. The coagulation cascade (especially thrombin), haemoglobin breakdown products, and inflammation all play a part in ICH-induced injury and could provide new therapeutic targets. Human imaging has shown that many ICH continue to expand after the initial ictus. Rebleeding soon after the initial haemorrhage is common and forms the basis of a current clinical trial using factor VIIa to prevent rebleeding. However, questions about mechanisms of injuries remain. There are conflicting data on the role of ischaemia in ICH and there is uncertainty over the role of clot removal in ICH therapy. The next decade should bring further information about the underlying mechanisms of ICH-induced brain injury and new therapeutic interventions for this severe form of stroke. This review addresses our current understanding of the mechanisms underlying ICH-induced brain injury.

Age Factors↗
PubMed2006

Tumor necrosis factor-alpha increases in the brain after intracerebral hemorrhage and thrombin stimulation.

OBJECTIVE: The goals of this study were 1) to determine the effects of intracerebral hemorrhage (ICH) on brain tumor necrosis factor (TNF)-alpha levels, which are still controversial; 2) to investigate the role of TNF-alpha in ICH-induced brain injury; 3) to examine the effects of thrombin on brain TNF-alpha levels; and 4) to elucidate the role of TNF-alpha in thrombin-induced neuroprotection. METHODS: Autologous whole blood and thrombin were injected into the right caudate of rats or mice. Brain TNF-alpha was then determined by enzyme-linked immunosorbent assay and immunohistochemistry. Brain edema and neurological deficits were also examined. RESULTS: Perihematomal TNF-alpha levels increased after ICH. ICH-induced brain edema was less in TNF-alpha knockout mice compared with wild-type mice (P < 0.05). Intracerebral infusion of thrombin also caused an increase in brain TNF-alpha levels. Thrombin preconditioning reduced thrombin-induced brain edema, but this effect was not blocked by a neutralizing TNF-alpha antibody. CONCLUSION: Increase of perihematomal TNF-alpha levels contributes to brain edema formation after ICH. Thrombin may be a major mediator of ICH-induced TNF-alpha production, but thrombin-induced brain tolerance may not be TNF-alpha mediated.

Animals↗
PubMed2006

Long-term effects of experimental intracerebral hemorrhage: the role of iron.

OBJECT: Intracerebral hemorrhage (ICH) causes brain atrophy and neurological deficits. The mechanisms of brain atrophy after ICH are poorly understood, although recent evidence suggests that some ICH-induced brain injury results from the products of hemoglobin degradation, including iron. In this study the authors examine the role of iron in brain atrophy and neurological deficits following ICH. METHODS: Male Sprague-Dawley rats received an infusion of either 100 microl autologous whole blood or saline into the right caudate. Hematoxylin and eosin staining was used for histological examination, and iron levels and ferritin immunoreactivities were also examined. Deferoxamine was used as an iron chelator. Over the duration of the experiment, the rats underwent behavioral testing (forelimb placing, forelimb use asymmetry, and corner turn tests). Brain atrophy in the caudate with prolonged neurological deficits occurred after ICH. Although partial functional recovery occurred with time, residual neurological deficits were still detectable at 3 months postprocedure. Iron accumulation and ferritin upregulation were present in the ipsilateral caudate. Deferoxamine reduced brain atrophy and improved behavioral outcomes, and it also reduced brain ferritin immunoreactivity. CONCLUSIONS: An ICH results in an accumulation of iron in the brain that is not cleared within 3 months and that contributes to brain tissue loss and neurological deficits posthemorrhage. Iron chelation may be a useful therapy for patients with ICH.

Animals↗
PubMed2005

The sensitivity and specificity of electrodiagnostic testing for the clinical syndrome of lumbar spinal stenosis.

STUDY DESIGN: Prospective, masked, double controlled diagnostic trial. OBJECTIVES: To determine the sensitivity and specificity of electrodiagnostic consultation (EDX) for the clinical syndrome of lumbar spinal stenosis. SUMMARY OF BACKGROUND DATA: EDX has been used for more than 50 years to diagnose spinal disorders but has not met the new standards of evidence-based medicine. METHODS: A total of 150 subjects (asymptomatic volunteers and patients with MRIs suggesting back pain or spinal stenosis; 55-80 years of age) underwent physiatrist history and physical examination, MRI, and review of this data by a neurosurgeon, with each clinician masked to any outside information, leading to a unanimous consensus on diagnosis in 55. After masked EDX testing, 7 subjects with undiagnosed neuromuscular disease were discovered. EDX findings were related to "clinical gold standard" diagnoses in 48 persons. RESULTS: Paraspinal mapping EMG score of >4 had 100% specificity and 30% sensitivity for stenosis compared with either the back pain or asymptomatic groups (each, P < 0.04). A composite limb and paraspinal fibrillation score had a sensitivity of 47.8% and specificity of 87.5% (P = 0.008), and H-wave sensitivity was 36.4, specificity 91.3 (P = 0.026) for stenosis versus all controls. CONCLUSIONS: This first masked study in the 60-year history of needle electromyography also introduces anatomically validated needle placement, quantified and reproducible examination of the paraspinal muscles, and dual control populations to EDX research in spinal disorders. EDX has statistically significant, clinically meaningful specificity for spinal stenosis and detects neuromuscular diseases that may masquerade as stenosis.

Aged↗
PubMed2005

The deleterious or beneficial effects of different agents in intracerebral hemorrhage: think big, think small, or is hematoma size important?

BACKGROUND AND PURPOSE: Thrombin, heme oxygenase, complement, microglia activation, and leukocyte infiltration are all actively upregulated in intracerebral hemorrhage (ICH). Experimental evidence suggests that all these factors are involved in ICH-induced brain injury. This suggests a scenario whereby ICH actively (through gene and protein upregulation) induces pathways that result in brain injury. SUMMARY OF REVIEW: In this comment, we suggest a potential answer to this conundrum. The upregulation of these factors may have been an evolutionary adaptation to limit brain injury during small hematomas (microbleeds). There is evidence that low levels of thrombin and heme oxygenase limit brain injury. In contrast, the excessive upregulation of these same factors may have a harmful effect after a large hematoma. CONCLUSIONS: The mechanisms upregulated to limit brain injury after microbleeds may also induce injury after large hematomas. The effect of hematoma size on the mechanisms involved in ICH-induced brain injury and the implications of any such effect on clinical therapies merit further investigation.

Animals↗
PubMed2005

Oxidative DNA injury after experimental intracerebral hemorrhage.

Our previous studies have demonstrated that DNA injury occurs in the brain after intracerebral hemorrhage (ICH). DNA damage can result from at least two pathways, either endonuclease-mediated DNA fragmentation or oxidative injury. The present study investigated the occurrence of the latter after ICH and the role of iron in such injury. Male Sprague-Dawley rats received an infusion of autologous whole blood or ferrous iron into the right basal ganglia. Control rats just had a needle insertion (sham). The rats were sacrificed 1, 3, or 7 days later. 8-Hydroxyl-2'-deoxyguanosine (8-OHdG) was analyzed by immunohistochemistry while the number of apurnic/apyrimidinic abasic sites (AP sites) was also quantified. 8-OHdG and AP sites are two hallmarks of DNA oxidation. Dinitrophenyl (DNP) was measured by Western blotting to compare the time course of protein oxidative damage to that of DNA. DNA repair Ku proteins were measured by Western blot analysis. DNA damage was also examined using DNA polymerase I-mediated biotin-dATP nick translation (PANT) labeling. An increase of 8-OHdG, AP sites and DNP levels and a decrease of Ku levels were observed. Abundant PANT-positive cells were also observed in the perihematomal area 3 days after ICH. In addition, intracerebral infusion of iron increased brain DNP levels and resulted in DNA injury. These results suggest that oxidative stress contributes to DNA damage and brain injury after ICH. Reducing DNA oxidative damage (for example, through iron chelation) may be a therapeutic target for ICH.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2005

Holo-transferrin and thrombin can interact to cause brain damage.

BACKGROUND AND PURPOSE: Previous studies have suggested that delayed release of hemoglobin degradation products, particularly iron, is involved in intracerebral hemorrhage (ICH)-induced brain injury. However, a recent study found evidence of iron-induced brain injury soon after ICH. This study, therefore, examined whether another iron-containing component of blood, holo-transferrin (holo-Tf), might also induce brain injury either alone or in combination with thrombin, another factor involved in early ICH-induced brain injury. METHODS: Male Sprague-Dawley rats received an intracerebral infusion of holo-Tf, apo (noniron-loaded)-Tf, thrombin, or a combination of Tf with thrombin into the right basal ganglia. The rats were euthanized 24 hours later for measurement of brain edema and assessment of DNA damage (single- and double-strand breaks and 8-hydroxyl-2'-deoxyguanosine immunohistochemistry). Iron distribution was examined histochemically. RESULTS: Holo-Tf, apo-Tf, and the dose of thrombin used (1 U) all failed to induce brain edema when administered alone. However, the combination of holo-Tf with thrombin (but not apo-Tf with thrombin) caused brain edema, DNA damage, and intracellular iron accumulation in the ipsilateral basal ganglia. CONCLUSIONS: These results suggest that in addition to hemoglobin-bound iron, Tf-bound iron may contribute to ICH-induced brain injury and that thrombin may contribute to the latter by facilitating cellular iron uptake.

Animals↗
PubMed2005

Estrogen therapy for experimental intracerebral hemorrhage in rats.

OBJECT: The aims of this study were to determine the following: whether there are sex differences in intracerebral hemorrhage (ICH) induced brain injury in rats, whether delayed administration of 17beta-estradiol can reduce ICH-induced brain damage, and whether these effects are estrogen receptor (ER)-dependent. METHODS: Male and female Sprague-Dawley rats received an infusion of 100 microl autologous whole blood into the right basal ganglia. Twenty-four hours later the rats were killed. The effects of 17beta-estradiol on ICH-induced brain injury were examined by measuring brain edema and neurological deficits. Both ER-alpha and hemeoxygenase (HO)-1 were investigated through Western blot and immunohistochemical analysis. Brain edema was significantly less severe in female compared with that in male rats. The ER antagonist ICI 182,780 exacerbated ICH-induced brain edema in female but not in male rats, indicating that ER-alpha activation during ICH is protective in female rats. Administration of exogenous 17beta-estradiol in male, but not in female, rats significantly attenuated brain edema, neurological deficits, and ICH-induced changes in HO-1 when given 2 hours after hemorrhage. The effects of exogenous 17beta-estradiol occurred through an ER-independent mechanism. CONCLUSIONS: Results in this study indicate that 17beta-estradiol could be a potential therapeutic agent for ICH.

Animals↗
PubMed2005

Propionibacterium infection associated with bovine pericardium dural allograft. Case report.

Propionibacteria are known to play a part in postneurosurgical infections, primarily those involving ventricular shunts. Nevertheless, little is known about the association between dural allografts and propionibacterium infections. Two patients underwent craniotomy for supratentorial meningiomas and each received a dural allograft. Both patients subsequently presented with delayed epidural fluid collections several weeks after surgery. Propionibacterium species was cultured in samples from both patients. The allografts were removed and the patients were treated with appropriate antibiotic agents; one patient underwent an interval craniectomy. Both patients demonstrated neuroimaging and clinical improvement after surgery and antiobiotic therapy. These cases demonstrate the association of propionibacterium infections with dural allografts. Furthermore, in patients with latent and indolent infections, Propionibacterium spp. should be suspected and treated appropriately.

Aged↗
PubMed2004

Intracerebral hemorrhage: effects of aging on brain edema and neurological deficits.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) is mostly a disease of the elderly, but most current experimental ICH models have used young animals. Age is an important factor in other forms of brain injury, affecting microglia and astrocyte reactions and plasticity. Therefore, the present study investigated the effects of aging on brain injury after ICH. METHODS: Young and aged (3 and 18 months old, respectively) male Sprague-Dawley rats received an intracerebral infusion of 100 microL autologous blood. Age-related changes in brain swelling, glial reaction, stress protein (heat shock proteins [HSPs] 27 and 32), and neurological deficits were examined. RESULTS: Brain swelling was more severe in old rats compared with young rats at 3 days after ICH (P<0.05). There were also more severe neurological deficits in the older rats at 1 day after ICH, which persisted for the 4 weeks of monitoring (P<0.05). The older rats also had stronger microglial activation and a greater perihematomal induction of HSP-27 and HSP-32 (P<0.05). In contrast, there was a weaker astrocytic reaction to the hematoma. CONCLUSIONS: ICH causes more severe brain swelling and neurological deficits in old rats. Clarification of the mechanisms of brain injury after ICH in the aging brain should help develop new therapeutic strategies for hemorrhagic brain injury.

Aging↗
PubMed2004

Adjacent segment disease after lumbar or lumbosacral fusion: review of the literature.

STUDY DESIGN: Review of the literature. OBJECTIVES: Review the definition, etiology, incidence, and risk factors associated with as well as potential treatment options. SUMMARY OF BACKGROUND DATA: The development of pathology at the mobile segment next to a lumbar or lumbosacral spinal fusion has been termed adjacent segment disease. Initially reported to occur rarely, it is now considered a potential late complication of spinal fusion that can necessitate further surgical intervention and adversely affect outcomes. METHODS: MEDLINE literature search. RESULTS: The most common abnormal finding at the adjacent segment is disc degeneration. Biomechanical changes consisting of increased intradiscal pressure, increased facet loading, and increased mobility occur after fusion and have been implicated in causing adjacent segment disease. Progressive spinal degeneration with age is also thought to be a major contributor. From a radiographic standpoint, reported incidence during average postoperative follow-up observation ranging from 36 to 369 months varies substantially from 5.2 to 100%. Incidence of symptomatic adjacent segment disease is lower, however, ranging from 5.2 to 18.5% during 44.8 to 164 months of follow-up observation. The rate of symptomatic adjacent segment disease is higher in patients with transpedicular instrumentation (12.2-18.5%) compared with patients fused with other forms of instrumentation or with no instrumentation (5.2-5.6%). Potential risk factors include instrumentation, fusion length, sagittal malalignment, facet injury, age, and pre-existing degenerative changes. CONCLUSION: Biomechanical alterations likely play a primary role in causing adjacent segment disease. Radiographically apparent, asymptomatic adjacent segment disease is common but does not correlate with functional outcomes. Potentially modifiable risk factors for the development of adjacent segment disease include fusion without instrumentation, protecting the facet joint of the adjacent segment during placement of pedicle screws,fusion length, and sagittal balance. Surgical management, when indicated, consists of decompression of neural elements and extension of fusion. Outcomes after surgery, however, are modest.

Adult↗
PubMed2004

Intracerebral hemorrhage in mice: model characterization and application for genetically modified mice.

Gene knockout or transgenic animals may assist in elucidating the mechanisms of brain injury after intracerebral hemorrhage (ICH). However, almost all commercially available transgenic or knockout animals are mice. The purpose of this study was to develop an ICH model in mice and to investigate the influence of gender and complement C5 genetic differences on outcome after ICH. Male and female C57BL/6 mice and C5-deficient and -sufficient control mice were anesthetized and then received an injection of 30 microL autologous whole blood into the right basal ganglia. Brain water content was studied at 1 and 3 days after ICH. Behavioral tests (fore-limb use asymmetry and corner turn test) were performed at 1, 3, 7, 14, 21, or 28 days after ICH. In male mice, brain water content was significantly increased in the ipsilateral basal ganglia 1 and 3 days after ICH, compared with saline injection controls (P < 0.01). There were marked neurological deficits 1 and 3 days after ICH, with progressive recovery over 28 days. In contrast, although brain edema and behavioral deficits were similar at 1 day after ICH in female and male mice, female mice showed reduced edema at 3 days and a faster recovery of behavioral deficits after ICH. 17 beta-estradiol treatment in male mice markedly reduced ICH-induced edema (P < 0.01). Brain water content was significantly increased in C5-deficient mice compared with C5-sufficient at 3 days after ICH (P < 0.05). These findings suggest that the mouse ICH model is a reproducible and feasible model. These results also suggest that gender and complement C5 are factors affecting brain injury after ICH.

Animals↗
PubMed2004

Intracerebral hemorrhage: pathophysiology and therapy.

Spontaneous intracerebral hemorrhage, from several sources, causes instantaneous mass effect, disruption of surrounding brain, and often an early neurological death. If the patient survives the initial event, the hematoma can lead to secondary brain injury, neurological deficits, and, occasionally, delayed fatality. The mechanisms that trigger pathophysiological changes in and around the hematoma are becoming better understood, offering new therapeutic opportunities.

Blood Coagulation↗
PubMed2004

Deferoxamine-induced attenuation of brain edema and neurological deficits in a rat model of intracerebral hemorrhage.

OBJECT: Previous studies undertaken by the authors have indicated that iron accumulation and oxidative stress in the brain contribute to secondary brain damage after intracerebral hemorrhage (ICH). In the present study the authors investigate whether deferoxamine, an iron chelator, can reduce ICH-induced brain injury. METHODS: Male Sprague-Dawley rats each received an infusion of 100 microl of autologous whole blood into the right basal ganglia and were killed 1, 3, or 7 days later. Iron distribution was examined histochemically (enhanced Perls reaction). The effects of deferoxamine on ICH-induced brain injury were examined by measuring brain edema and neurological deficits. Immunohistochemical analysis was performed to investigate 8-hydroxyl-2'-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, and Western blot analysis was performed to measure the amount of apurinic/apyrimidinic endonuclease/redox effector factor-1 (APE/Ref-1), a repair mechanism for DNA oxidative damage. Iron accumulation was observed in the perihematomal zone from 1 day after ICH. Deferoxamine attenuated brain edema, neurological deficits, and ICH-induced changes in 8-OHdG and APE/Ref-1. CONCLUSIONS: Deferoxamine and other iron chelators may be potential therapeutic agents for ICH. They may act by reducing the oxidative stress caused by the release of iron from the hematoma.

Animals↗