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Dr. Sheldon Jordan, MD
Neurologist, Pain Medicine
35 years of experience

Video profile


Education ?

Medical School Score Rankings
University of California at Los Angeles (1977)
Top 25%

Awards & Distinctions ?

Castle Connolly's Top Doctors™ (2012 - 2013)
Patients' Choice Award (2010, 2014 - 2015)
American Board of Psychiatry and Neurology

Affiliations ?

Dr. Jordan is affiliated with 2 hospitals.

Hospital Affiliations



  • St. John's Hospital & Health Center *
    1328 22nd St, Santa Monica, CA 90404
    Top 25%
  • Saint John's Health Center
    1328 22nd St, Santa Monica, CA 90404
  • * This information was reported to Vitals by the doctor or doctor's office.

    Publications & Research

    Dr. Jordan has contributed to 39 publications.
    Title Combining Ultrasonography and Electromyography for Botulinum Chemodenervation Treatment of Thoracic Outlet Syndrome: Comparison with Fluoroscopy and Electromyography Guidance.
    Date October 2007
    Journal Pain Physician

    BACKGROUND: Botulinum chemodenervation has been increasingly used for treating conditions characterized by muscular pain and dystonia. Complication rates commonly exceed 10 percent in published accounts due to an inadvertent spread of toxin. Various techniques of precision targeting have been described to minimize undesirable toxin effects. The present study reports on a clinical experience combining ultrasonography and electromyography in order to demonstrate how favorably this approach compares to previously described techniques in terms of minimizing complications while maintaining efficacy. DESIGN: Retrospective case series METHODS: The present study is a retrospective clinical analysis of patients treated with botulinum toxin using 2 different combined targeting techniques; one using ultrasonography and electromyography and the other using fluoroscopy and electromyography. RESULTS: Combined ultrasonography and electromyography was used in 77 of 245 procedures; in 168 procedures, fluoroscopy and electromyography was used. There were no complications with ultrasonography guided procedures; the complication rate for combined fluoroscopy and electromyography was 1.8 percent (3/168; Fisher exact p = 0.3206). For combined ultrasonography and electromyography, after 70 out of 77 procedures (91%) there was a good outcome compared to 136 out of 168 (81%) after procedures utilizing a combination of fluoroscopy and electromyography (Fisher exact p= 0.331). CONCLUSIONS: There was no significant difference in complication rate or successful outcomes comparing the 2 forms of imaging guidance when targeting muscles for botulinum injection. Since outcomes are comparable, other factors such as cost and radiation exposure may be considered in choosing which imaging modality to use.

    Title Assessment: Use of Epidural Steroid Injections to Treat Radicular Lumbosacral Pain: Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.
    Date October 2007
    Journal Neurology
    Title Differentiation of Thoracic Outlet Syndrome from Treatment-resistant Cervical Brachial Pain Syndromes: Development and Utilization of a Questionnaire, Clinical Examination and Ultrasound Evaluation.
    Date July 2007
    Journal Pain Physician

    OBJECTIVE: The present study was undertaken to determine which factors differentiate patients with a good outcome after treatment for Thoracic Outlet Syndrome (TOS) from patients with a poor outcome. METHODS: A total of 85 patients, who were examined during one year, had at least 6 months of follow up after treatment for TOS with either surgery or botulinum chemodenervation. RESULTS: Socioeconomic factors of work disability or workers' compensation claims did not differentiate treatment-responsive TOS from treatment-resistant cases. There was no difference between the 2 groups regarding the presence of anomalous anatomy detected by ultrasonography or regarding the presence of subclavian artery flow acceleration or occlusion detected by duplex sonography. Several factors were noted more frequently in treatment-resistant patients: sensory complaints extending beyond lower trunk dermatomes (42% vs. 10%), weakness extending beyond lower trunk myotomes (19% vs. 2%), histories of previous non-TOS surgery of the neck or upper limbs (50% vs.17%), comorbidities of fibromyalgia or complex regional pain syndrome (81% vs. 12%), and depression (35% vs. 10%). Treatment-resistant patients complained about more widespread functional impairments on a validated Cervical Brachial Symptom Questionnaire (CBSQ) than treatment-responsive patients. Resistant cases responded less often to a scalene test block (38% vs. 100%), which is designed to simulate the effects of targeted treatment. CONCLUSION: In summary, compared to patients with a good outcome after targeted treatment, patients with a poor outcome had more diffuse complaints and responded less often to a scalene test block.

    Title Giving People a Voice: Reflections on Conducting Interviews with Participants Experiencing Communication Impairment.
    Date July 2005
    Journal Journal of Advanced Nursing

    AIM: The aim of this paper is to describe the various strategies employed to mitigate communication impairments and to argue that illness experiences may be captured through methods other than audio-tape recordings of spoken words. BACKGROUND: This paper explores issues surrounding the collection of interview data from participants experiencing communication impairments. It derives from a qualitative interview study, which enquired into experiences of living with a percutaneous endoscopic gastrostomy. This is an artificial route created directly into the stomach for long-term delivery of nutrition to people who are unable to take nutrition via the normal route. However, in many cases the physical impairments that led to their requirement for this form of feeding also made speech, and hence interviewing, very difficult. DISCUSSION: Capturing illness experiences from participants with impaired communication requires a reconsideration of both practical strategies and broader methodological issues. In addition to the adaptation of data generation strategies a re-examination of the complexities inherent in the meaning of 'patient experience' is required. This paper explores the utility of verbal and other interactional input from carers to explore further dimensions of this experience. CONCLUSION: Qualitative research that seeks to capture the meanings of illness from the patient's perspective needs to be adapted to embrace different modes of communicating the illness experience.

    Title Sciatica of Nondisc Origin and Piriformis Syndrome: Diagnosis by Magnetic Resonance Neurography and Interventional Magnetic Resonance Imaging with Outcome Study of Resulting Treatment.
    Date March 2005
    Journal Journal of Neurosurgery. Spine

    OBJECT: Because lumbar magnetic resonance (MR) imaging fails to identify a treatable cause of chronic sciatica in nearly 1 million patients annually, the authors conducted MR neurography and interventional MR imaging in 239 consecutive patients with sciatica in whom standard diagnosis and treatment failed to effect improvement. METHODS: After performing MR neurography and interventional MR imaging, the final rediagnoses included the following: piriformis syndrome (67.8%), distal foraminal nerve root entrapment (6%), ischial tunnel syndrome (4.7%), discogenic pain with referred leg pain (3.4%), pudendal nerve entrapment with referred pain (3%), distal sciatic entrapment (2.1%), sciatic tumor (1.7%), lumbosacral plexus entrapment (1.3%), unappreciated lateral disc herniation (1.3%), nerve root injury due to spinal surgery (1.3%), inadequate spinal nerve root decompression (0.8%), lumbar stenosis (0.8%), sacroiliac joint inflammation (0.8%), lumbosacral plexus tumor (0.4%), sacral fracture (0.4%), and no diagnosis (4.2%). Open MR-guided Marcaine injection into the piriformis muscle produced the following results: no response (15.7%), relief of greater than 8 months (14.9%), relief lasting 2 to 4 months with continuing relief after second injection (7.5%), relief for 2 to 4 months with subsequent recurrence (36.6%), and relief for 1 to 14 days with full recurrence (25.4%). Piriformis surgery (62 operations; 3-cm incision, transgluteal approach, 55% outpatient; 40% with local or epidural anesthesia) resulted in excellent outcome in 58.5%, good outcome in 22.6%, limited benefit in 13.2%, no benefit in 3.8%, and worsened symptoms in 1.9%. CONCLUSIONS: This Class A quality evaluation of MR neurography's diagnostic efficacy revealed that piriformis muscle asymmetry and sciatic nerve hyperintensity at the sciatic notch exhibited a 93% specificity and 64% sensitivity in distinguishing patients with piriformis syndrome from those without who had similar symptoms (p < 0.01). Evaluation of the nerve beyond the proximal foramen provided eight additional diagnostic categories affecting 96% of these patients. More than 80% of the population good or excellent functional outcome was achieved.

    Title Heading and Head Injuries in Soccer.
    Date September 2001
    Journal Sports Medicine (auckland, N.z.)

    In the world of sports, soccer is unique because of the purposeful use of the unprotected head for controlling and advancing the ball. This skill obviously places the player at risk of head injury and the game does carry some risk. Head injury can be a result of contact of the head with another head (or other body parts), ground, goal post, other unknown objects or even the ball. Such impacts can lead to contusions, fractures, eye injuries, concussions or even, in rare cases, death. Coaches, players, parents and physicians are rightly concerned about the risk of head injury in soccer. Current research shows that selected soccer players have some degree of cognitive dysfunction. It is important to determine the reasons behind such deficits. Purposeful heading has been blamed, but a closer look at the studies that focus on heading has revealed methodological concerns that question the validity of blaming purposeful heading of the ball. The player's history and age (did they play when the ball was leather and could absorb significant amounts of water), alcohol intake, drug intake, learning disabilities, concussion definition and control group use/composition are all factors that cloud the ability to blame purposeful heading. What does seem clear is that a player's history of concussive episodes is a more likely explanation for cognitive deficits. While it is likely that the subconcussive impact of purposeful heading is a doubtful factor in the noted deficits, it is unknown whether multiple subconcussive impacts might have some lingering effects. In addition, it is unknown whether the noted deficits have any affect on daily life. Proper instruction in the technique is critical because if the ball contacts an unprepared head (as in accidental head-ball contacts), the potential for serious injury is possible. To further our understanding of the relationship of heading, head injury and cognitive deficits, we need to: learn more about the actual impact of a ball on the head, verify the exposure to heading at all ages and competitive levels, determine stable estimates of concussive injury rates across the soccer spectrum, conduct prospective longitudinal studies on soccer players focusing on exposure, injury and cognition, and determine the minimum safe age to begin instruction on the skill of heading. Only then will we be able to speak with some authority on the issue of heading and head injuries in soccer.

    Title Selective Botulinum Chemodenervation of the Scalene Muscles for Treatment of Neurogenic Thoracic Outlet Syndrome.
    Date January 2001
    Journal Annals of Vascular Surgery

    Patients with thoracic outlet syndrome (TOS) who improve temporarily after anesthetic blockade of the anterior scalene muscles have been shown to improve after ultimate surgical decompressions at the interscalene triangle. Anesthetic blockade of the scalene muscles, even with the addition of steroids, however, rarely produces any prolonged relief as patients are awaiting definitive surgery. The present study was undertaken to determine if more effective and prolonged relief might be obtained with electrophysiologically and fluoroscopically guided selective injection of the scalene muscles with botulinum toxin, which has been used in the past for treating conditions associated with spasm of cervical muscles. In 14 of 22 patients (64%) with a clinical diagnosis of TOS, there was more than a 50% reduction of symptoms measured by a 101-point scale for at least 1 month after botulinum chemodenervation of the scalene muscles. Only 4 of the 22 patients (18%) had a 50% reduction of symptoms for at least 1 month after injection with lidocaine and steroids. In no patient were the results of lidocaine and steroid injection superior to botulinum chemodenervation. Chemodenervation had a mean duration of effect of 88 days. No significant side effects were encountered with botulinum chemodenervation except for mild transient dysphagia in two cases. These results appear to demonstrate that botulinum chemodenervation of the scalene muscles may be helpful in alleviating symptoms in patients with TOS awaiting definitive surgical decompression.

    Title Nitric Oxide Regulation of Cgmp Production in Osteoclasts.
    Date March 2000
    Journal Journal of Cellular Biochemistry

    Bone resorption by osteoclasts is modified by agents that affect cyclic guanosine monophosphate (cGMP), but their relative physiological roles, and what components of the process are present in osteoclasts or require accessory cells such as osteoblasts, are unclear. We studied cGMP regulation in avian osteoclasts, and in particular the roles of nitric oxide and natriuretic peptides, to clarify the mechanisms involved. C-type natriuretic peptide drives a membrane guanylate cyclase, and increased cGMP production in mixed bone cells. However, C-type natriuretic peptide did not increase cGMP in purified osteoclasts. By contrast, osteoclasts did produce cGMP in response to nitric oxide (NO) generators, sodium nitroprusside or 1-hydroxy-2-oxo-3,3-bis(3-aminoethyl)-1-triazene. These findings indicate that C-type natriuretic peptide and NO modulate cGMP in different types of bone cells. The activity of the osteoclast centers on HCI secretion that dissolves bone mineral, and both NO generators and hydrolysis-resistant cGMP analogues reduced bone degradation, while cGMP antagonists increased activity. NO synthase agonists did not affect activity, arguing against autocrine NO production. Osteoclasts express NO-activated guanylate cyclase and cGMP-dependent protein kinase (G-kinase). G-kinase reduced membrane HCI transport activity in a concentration-dependent manner, and phosphorylated a 60-kD osteoclast membrane protein, which immunoprecipitation showed is not an H+-ATPase subunit. We conclude that cGMP is a negative regulator of osteoclast activity. cGMP is produced in response to NO made by other cells, but not in response to C-type natriuretic peptide. G-kinase modulates osteoclast membrane HCI transport via intermediate protein(s) and may mediate cGMP effects in osteoclasts.

    Title Intracellular Calcium Puffs in Osteoclasts.
    Date January 2000
    Journal Experimental Cell Research

    We studied intracellular calcium ([Ca(2+)](i)) in acid-secreting bone-attached osteoclasts, which produce a high-calcium acidic extracellular compartment. Acid secretion and [Ca(2+)](i) were followed using H(+)-restricted dyes and fura-2 or fluo-3. Whole cell calcium of acid-secreting osteoclasts was approximately 100 nM, similar to cells on inert substrate that do not secrete acid. However, measurements in restricted areas of the cell showed [Ca(2+)](i) transients to 500-1000 nM consistent with calcium puffs, transient (millisecond) localized calcium elevations reported in other cells. Spot measurements at 50-ms intervals indicated that puffs were typically less than 400 ms. Transients did not propagate in waves across the cell in scanning confocal measurements. Calcium puffs occurred mainly over regions of acid secretion as determined using lysotracker red DND99 and occurred at irregular periods averaging 5-15 s in acid secreting cells, but were rare in lysotracker-negative nonsecretory cells. The calmodulin antagonist trifluoperazine, cell-surface calcium transport inhibitors lanthanum or barium, and the endoplasmic reticulum ATPase inhibitor thapsigargin had variable acute effects on the mean [Ca(2+)](i) and puff frequency. However, none of these agents prevented calcium puff activity, suggesting that the mechanism producing the puffs is independent of these processes. We conclude that [Ca(2+)](i) transients in osteoclasts are increased in acid-secreting osteoclasts, and that the puffs occur mainly near the acid-transporting membrane. Cell membrane acid transport requires calcium, suggesting that calcium puffs function to maintain acid secretion. However, membrane H(+)-ATPase activity was insensitive to calcium in the 100 nM-1 microM range. Thus, any effects of calcium puffs on osteoclastic acid transport must be indirect.

    Title Parathyroid Hormone-regulated Production of Stem Cell Factor in Human Osteoblasts and Osteoblast-like Cells.
    Date March 1999
    Journal Biochemical and Biophysical Research Communications

    We investigated stem cell factor (SCF) expression in osteoblasts because mast cells, which occur ectopically in hyperparathyroid bone, are induced by SCF. Nontransformed osteoblasts and Saos2 or MG63 cells expressed SCF in response to PTH. Western analysis showed only large, cell-associated isoforms, Mrs approximately 40-48 kD. Transfection of MG63 cells with plasmids expressing antisense SCF mRNA eliminated immunoreactive SCF. Sequencing osteoblast SCF cDNAs showed that exon 6 was omitted. mRNAs without exon 6 produce membrane-associated SCF isoforms in rodents, suggesting that human SCFs are processed similarly. The major osteoblastic SCF mRNA, approximately 5 kB, was augmented by PTH. Neither protein or mRNA was increased by vitamin D, however, 6-7 kB transcripts were predominant in other tissues but not detectable in osteoblasts. We conclude that osteoblasts express SCF in response to PTH, with mRNA and protein processing differences relative to other cells. SCF stimulates osteoclasts, suggesting that PTH-induced osteoblastic SCF functions to accelerate bone turnover. Mast cells may occur due to SCF overexpression at extreme PTH levels.

    Title Are Brain Injuries a Significant Problem in Soccer?
    Date March 1999
    Journal Clinics in Sports Medicine

    This article examines the types of forces that the brain is subjected to in soccer, secondary to both acute brain injury and repetitive heading of the ball. The incidence of acute brain injury is reviewed, as well as studies documenting the effects of heading the ball. Finally, 10 actions are proposed that would make soccer a safer sport with respect to brain injuries and provide avenues for further study in this area.

    Title Tyrosine Kinase Inhibitor Effects on Avian Osteoclastic Acid Transport.
    Date January 1999
    Journal The American Journal of Clinical Nutrition

    We found that tyrosine kinase pp60(c-src) coisolates with acid-transporting osteoclast membranes and hypothesized that this kinase regulates hydrochloric acid transport. We assayed the membrane acid transport and bone degradation effects of tyrosine kinase inhibitors in avian osteoclasts. Isoflavone, tyrphostin, and benzoquinonoid inhibitors were compared with inactive analogues to determine nonspecific effects. Acid-secreting membranes, isolated by nitrogen cavitation, were assayed as reconstituted vesicles by using acridine orange to indicate ATP-dependent hydrogen ion transport. The soy isoflavone genistein and the benzoquinonoid antibiotic herbimycin inhibited hydrochloric acid transport with 50% inhibition at approximately 10 and approximately 2 micromol/L, respectively; effects appeared in <2 min and were reversible. In membrane incubated with inhibitors, the herbimycin effect also inhibited Cl- transport by variable amounts, suggesting that this compound affects Cl- channel activity. However, genistein and tyrphostins did not produce chloride dependent effects. After 30 min with ATP, tyrphostin A47 irreversibly inhibited hydrochloric acid transport with 50% inhibition at approximately 10 micromol/L. Tyrphostin A25 and controls, tyrphostin A1 and daidzein (a genistein congener), were inactive despite preincubation. Osteoclastic bone resorption was more sensitive to the inhibitors over 3-5-d assays than was membrane acid transport, except for tyrphostins. Herbimycin and genistein inhibited bone resorption with half maximal effects at 0.5 and 10 micromol/L and complete inhibition at 3 d in 1 and 20 micromol/L, respectively. None of the tyrphostins, including A47, nor daidzein inhibited resorption to >20 micromol/L. We conclude that tyrosine kinase inhibition directly inhibits osteoclast membrane hydrochloric acid transport; differences among inhibitors may reflect chemical reactivity and permeability.

    Title Diagnosis of Thoracic Outlet Syndrome Using Electrophysiologically Guided Anterior Scalene Blocks.
    Date July 1998
    Journal Annals of Vascular Surgery

    There is no "gold standard" for diagnosing thoracic outlet compression syndrome (TOS), however, anesthetic blocks of the anterior scalene muscle (ASM) have been used as a means of predicting which patients may benefit from surgical decompression. The standard technique of using surface landmarks often results in inadvertent somatic block and sympathetic block because there is no reliable verification of needle tip localization. The present study was undertaken to determine if needle tip localization can be improved by using electrophysiological guidance. ASM blocks were performed for patients with a diagnosis of possible TOS. An insulated hypodermic needle was inserted into the ASM which was identified during electromyogram (EMG) activation maneuvers. Stimulation was performed to make sure that the needle tip was not in the brachial plexus. Local anesthetic was instilled and the intensity of pain induced by TOS stress maneuvers was compared to pain ratings obtained after control injections. The ASM could be identified electromyographically in all 122 cases. There were no instances of inadvertent somatic block nor sympathetic block. Of 38 patients who underwent surgical decompression of the thoracic outlet, 30 of 32 (94%) with a positive block had a good outcome compared with 3 of 6 (50%) who underwent surgery in spite of a negative block. Electrophysiological guidance facilitates accurate needle tip placement in the performance of ASM blocks; the results of these blocks appear to correlate with surgical outcomes.

    Title Differential Effects of Tamoxifen-like Compounds on Osteoclastic Bone Degradation, H(+)-atpase Activity, Calmodulin-dependent Cyclic Nucleotide Phosphodiesterase Activity, and Calmodulin Binding.
    Date September 1997
    Journal Journal of Cellular Biochemistry

    We studied effects of calmodulin antagonists on osteoclastic activity and calmodulin-dependent HCl transport. The results were compared to effects on the calmodulin-dependent phosphodiesterase and antagonist-calmodulin binding affinity. Avian osteoclast degradation of labeled bone was inhibited approximately 40% by trifluoperazine or tamoxifen with half-maximal effects at 1-3 microM. Four benzopyrans structurally resembling tamoxifen were compared: d-centchroman inhibited resorption 30%, with half-maximal effect at approximately 100 nM, cischroman and CDRI 85/287 gave 15-20% inhibition, and l-centchroman was ineffective. No benzopyran inhibited cell attachment or protein synthesis below 10 microM. However, ATP-dependent membrane vesicle acridine transport showed that H(+)-ATPase activity was abolished by all compounds with 50% effects at 0.25-1 microM. All compounds also inhibited calmodulin-dependent cyclic nucleotide phosphodiesterase at micromolar calcium. Relative potency varied with assay type, but d- and l-centchroman, surprisingly, inhibited both H(+)-ATPase and phosphodiesterase activity at similar concentrations. However, d- and l-centchroman effects in either assay diverged at nanomolar calcium. Of benzopyrans tested, only the d-centchroman effects were calcium-dependent. Interaction of compounds with calmodulin at similar concentrations were confirmed by displacement of labeled calmodulin from immobilized trifluoperazine. Thus, the compounds tested all interact with calmodulin directly to varying degrees, and the observed osteoclast inhibition is consistent with calmodulin-mediated effects. However, calmodulin antagonist activity varies between specific reactions, and free calcium regulates specificity of some interactions. Effects on whole cells probably also reflect other properties, including transport into cells.

    Title Regulation of Osteoclastic Bone Resorption by Glucose.
    Date July 1997
    Journal Biochemical and Biophysical Research Communications

    Osteoclasts degrade bone by pumping molar quantities of HCl to dissolve the calcium salts of bone, an energy intensive process evidently supported by abundant mitochondria. This is the first study to directly examine the ability of various metabolites to serve as potential energy sources for osteoclastic bone resorption. Glucose, and to a lesser extent lactate, supported osteoclastic bone degradation. However, fatty acids (palmitate, myristate and stearate), essential amino acids plus 20 mM alanine, or ketone bodies (acetoacetate, beta-hydroxybutyrate and alpha-ketoglutarate) did not support bone degradation. Resorption declined to 10-30% of glucose controls when fatty acids or ketoacids were substituted for glucose. Resorption was glucose concentration dependent, with maximal activity at approximately 7 mM (K(M) approximately 3 mM). Glucose transport was linear for approximately 15 minutes, specific for D-glucose, and inhibited by cytochalasin B. Osteoclasts cultured on bone transported glucose at almost twice the rate of those off bone (Vmax 23 versus 13 nmols/mg/min, respectively) and medium acid accumulation paralleled glucose uptake, while the K(M) was unchanged. We conclude that glucose is the principal energy source required for bone degradation. Further, characteristics of glucose transport are consistent with the hypothesis that fluctuations in serum glucose concentration are an important component in regulation of osteoclastic bone degradation.

    Title Effects of Cell Culture Time and Bone Matrix Exposure on Calmodulin Content and Atp-dependent Cell Membrane Acid Transport in Avian Osteoclasts and Macrophages.
    Date January 1997
    Journal Journal of Cellular Physiology

    Osteoclasts mediate bone resorption by secretion at the site of bone attachment. This process depends on calmodulin concentrated at a specialized acid-secreting membrane. We hypothesized that increased calmodulin and bone attachment were required for acid secretion. We tested this by studying calmodulin, bone attachment, and membrane acid transport in osteoclasts and their precursor mononuclear cells. Osteoclasts and macrophages were isolated from medullary bone of hens; cell fractions were prepared after culturing cells with or without bone. Calmodulin was visualized by Western analysis; calmodulin mRNA was determined by Northern hybridization, and ATP-dependent membrane acid transport was assayed by acridine orange uptake. Calmodulin decreased in osteoclasts cultured without bone. Calmodulin in isolated macrophages was approximately 25% of osteoclast levels, but increased several fold by 5 days. Bone had no effect. Calmodulin mRNA was similar in osteoclasts with or without bone. However, only osteoclasts cultured with bone retained acid transport capacity. Macrophage calmodulin mRNA was not affected by bone, but increased three fold by day 5, paralleling protein production. Macrophages developed acid transport capacity at 3-5 days, but at lower levels than osteoclasts, and bone had no measurable effect. Chicken cells express 1.6 kb and inducible 1.9 kb calmodulin transcripts; in macrophages and osteoclasts, the 1.9 kb transcript predominated. We conclude that, following isolation, calmodulin levels decline in osteoclasts via a post-transcriptional mechanism. In cultured macrophages, by contrast, calmodulin mRNA, protein, and acid secretion increase with time independently of bone substrate, possibly reflecting differentiation in vitro. Increased calmodulin correlated with membrane acid transport capacity in both cell types. The macrophage findings indicate that stimuli other than bone influence acid transport capacity in this family of cells.

    Title Acute and Chronic Brain Injury in United States National Team Soccer Players.
    Date December 1996
    Journal The American Journal of Sports Medicine

    We designed a study to determine whether chronic encephalopathy occurs in elite, active soccer players resulting from repetitive heading of the soccer ball. Studies have suggested that the cumulative effects of heading a ball can cause a chronic brain syndrome similar to dementia pugilistica, which is seen in professional boxers. Twenty of 25 members of the U.S. Men's National Soccer Team training camp (average age, 24.9; average years of soccer, 17.7), who completed a questionnaire on head injury symptoms and had magnetic resonance imaging of the brain, were compared with 20 age-matched male elite track athletes. The soccer players were surveyed about playing position, teams, number of headers, acute head injuries, and years of playing experience. An exposure index to headers was developed to assess a dose-response effect of chronic heading. The soccer and track groups were questioned regarding alcohol use and history of acute head traumas. Questionnaire analysis and magnetic resonance imaging demonstrated no statistical differences between the two groups. Among the soccer players, symptoms and magnetic resonance imaging findings did not correlate with age, years of play, exposure index results, or number of headers. However, reported head injury symptoms, especially in soccer players, correlated with histories of prior acute head injuries (r = 0.63). These findings suggest that any evidence of encephalopathy in soccer players relates more to acute head injuries received playing soccer than from repetitive heading.

    Title Variable Effects of Tyrosine Kinase Inhibitors on Avian Osteoclastic Activity and Reduction of Bone Loss in Ovariectomized Rats.
    Date November 1996
    Journal Journal of Cellular Biochemistry

    We compared the effects of the tyrosine kinase inhibitor genistein, a naturally occurring isoflavone, to those of tyrphostin A25, tyrphostin A47, and herbimycin on avian osteoclasts in vitro. Inactive analogs daidzein and tyrphostin A1 were used to control for nonspecific effects. None of the tyrosine kinase inhibitors inhibited bone attachment. However, bone resorption was inhibited by genistein and herbimycin with ID50s of 3 microM and 0.1 microM, respectively; tyrphostins and daidzein were inactive at concentrations below 30 microM, where nonspecific effects were noted. Genistein and herbimycin thus inhibit osteoclastic activity via a mechanism independent of cellular attachment, and at doses approximating those inhibiting tyrosine kinase autophosphorylation in vitro; the tyrphostins were inactive at meaningful doses. Because tyrosine kinase inhibitors vary widely in activity spectrum, effects of genistein on cellular metabolic processes were compared to herbimycin. Unlike previously reported osteoclast metabolic inhibitors which achieve a measure of selectivity by concentrating on bone, neither genistein nor herbimycin bound significantly to bone. Osteoclastic protein synthesis, measured as incorporation of 3H-leucine, was significantly inhibited at 10 microM genistein, a concentration greater than that inhibiting bone degradation, while herbimycin reduced protein synthesis at 10 nM. These data suggested that genistein may reduce osteoclastic activity at pharmacologically attainable levels, and that toxic potential was lower than that of herbimycin. To test this hypothesis in a mammalian system, bone mass was measured in 200 g ovariectomized rats treated with 44 mumol/day genistein, relative to untreated controls. During 30 d of treatment, weights of treated and control group animals were indistinguishable, indicating no toxicity, but femoral weight in the treated group was 12% greater than controls (P < 0.05). Our data indicate that the isoflavone inhibitor genistein suppresses osteoclastic activity in vitro and in vivo at concentrations consistent with its ID50s on tyrosine kinases, with a low potential for toxicity.

    Title Integrin Expression in Breast Cancer Cytology: a Novel Predictor of Axillary Metastasis.
    Date July 1996
    Journal European Journal of Surgical Oncology : the Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology

    The integrins are heterodimeric transmembrane receptors of varying alpha and beta subunits that modulate cell adhesion to each other and to the extracellular matrix. Loss of integrin expression on primary breast cancer frozen sections measured by immunohistochemistry may be related to the presence of axillary metastasis. The clinical application of this finding would be increased if integrin expression could also be shown to be reliably measured on breast cancer cells obtained by fine needle aspiration cytology. Axillary operations may be planned as a single stage procedure from outpatients, and neoadjuvant therapy protocols may be developed without surgery to the axilla. Expression of the alpha 1, alpha 2, alpha 3, alpha 6, alpha v, beta 1, beta 3 and beta 5 integrin subunits were measured by immunohistochemistry and immunocytochemistry in 58 patients. Integrin measurement by both these methods were found to be closely associated using the kappa-test. Loss of expression of the alpha 1, alpha 2, alpha 3, alpha 6, alpha v, beta 1 and beta 5 integrin subunits measured by cytology and histology were each related to positive nodal status (chi(2) test). Measuring integrin expression on cytology is of clinical value and may prove to have prognostic significance.

    Title Regulation of Avian Osteoclastic H+ -atpase and Bone Resorption by Tamoxifen and Calmodulin Antagonists. Effects Independent of Steroid Receptors.
    Date July 1996
    Journal The Journal of Biological Chemistry

    We used highly purified avian osteoclasts and isolated membranes from osteoclasts to study effects of tamoxifen, 4-hydroxytamoxifen, calmodulin antagonists, estrogen, diethylstilbestrol, and the anti-estrogen ICI 182780 on cellular degradation of 3H-labeled bone in vitro and on membrane HCl transport. Bone resorption was reversibly inhibited by tamoxifen, 4-hydroxytamoxifen, and trifluoperazine with IC50 values of approximately 1 microM. Diethylstilbestrol and 17-beta-stradiol had no effects on bone resorption at receptor-saturating concentrations, while ICI 182780 inhibited bone resorption at concentrations greater than 1 microM. At these concentrations ICI 182780, like tamoxifen, inhibits calmodulin-stimulated cyclic nucleotide phosphodiesterase activity. Membrane HCl transport, assessed by ATP-dependent acridine orange uptake, was unaffected by 17-beta-estradiol and diethylstilbestrol at concentrations up to 10 microM, while ICI greater than 1 microM. In contrast HCl transport was inhibited by tamoxifen, 4-hydroxytamoxifen, and the calmodulin antagonists, trifluoperazine and the calmidazolium, with IC50 values of 0.25-1.5 microM. These results suggested the presence of a membrane-associated non-steroid receptor for tamoxifen in osteoclasts. Tamoxifen binding studies demonstrated saturable binding in the osteoclast particulate fraction, but not in the nuclear or cytosolic fractions. Membranes enriched in ruffled border by differential centrifugation following nitrogen cavitation showed binding consistent with one site, Kd approximately microM. Our findings indicate that tamoxifen inhibits osteoclastic HCl transport by binding membrane-associated target(s), probably similar or related to calmodulin antagonist targets. Further, effects of estrogens or highly specific anti-estrogens on bone turnover do not support the hypothesis of a direct effect on osteoclasts by these compounds in this species.

    Title Avian Cathepsin B Cdna: Sequence and Demonstration That Mrnas of Two Sizes Are Produced in Cell Types Producing Large Quantities of the Enzyme.
    Date September 1995
    Journal Biochimica Et Biophysica Acta

    Overlapping cDNA fragments encoding avian cathepsin B were cloned from an osteoclast cDNA library and sequenced. The primary structure of the prepro enzyme deduced from this sequence has 340 amino acids. The mature portion of the enzyme is 80% identical with murine cathepsin B; regions found in other papain superfamily enzymes are conserved. In osteoclasts and cultured macrophages, which produce large quantities of cathepsin B, mRNAs of 1.8 and 2.4 kb are produced in approximately equal quantities, while cells producing smaller quantities of the enzyme produce predominantly the 2.4 kb form. This variation in mRNAs suggests transcriptional differences related to production of large quantities of the enzyme.

    Title The Expression of Intercellular Adhesion Molecule-1 and the Beta 1-integrins in Asthma.
    Date December 1994
    Journal The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology

    Expression of intercellular adhesion molecule-1 (ICAM-1) appears to be important to the development of bronchial hyperresponsiveness and eosinophilia in Ascaris sensitized monkeys. Beta 1-integrins are expressed on epithelial cells, and may contribute to adherence of epithelial cells to the basement membrane. The aim of this study was to determine whether adhesion receptor expression was altered in human asthmatic bronchial epithelium. Using monoclonal antibody staining, we have examined the expression of ICAM-1 and the alpha 1-alpha 6-subunits of the beta 1-integrin family in bronchial mucosal biopsies from 33 asthmatic and 13 nonasthmatic subjects. The epithelium was positive for ICAM-1 in 26 out of 33 asthmatics, although negative in all 13 nonasthmatics. ICAM-1 expression was not associated with bronchial responsiveness or with medication requirements. Beta 1-integrin staining showed that alpha 2-, alpha 3- and alpha 6-subunits stained the epithelium in all cases. Alpha 4 staining was weakly positive in the epithelium in five asthmatics. Alpha 5 staining was weak in asthmatics and normals. Alpha 4 and alpha 6-subunits also stained inflammatory cells. Epithelial upregulation of ICAM-1 is present in asthma. Beta 1-integrins with alpha 2-, alpha 3- and alpha 6-subunits appear to be constitutively expressed in bronchial epithelium.

    Title Placebo-controlled Immunopathologic Study of Four Months of Inhaled Corticosteroids in Asthma.
    Date August 1994
    Journal American Journal of Respiratory and Critical Care Medicine

    The effect of prolonged inhaled corticosteroid treatment on bronchial immunopathology was assessed in 25 nonsmoking mildly asthmatic subjects previously receiving intermittent inhaled beta 2-agonist alone. Inhaled beclomethasone dipropionate (BDP), 500 micrograms twice per day or placebo was administered for 4 mo in a double-blind parallel group study. Histamine bronchial provocation, fiberoptic bronchoscopic biopsy, and bronchoalveolar lavage (BAL) were performed before and after treatment. There was no difference in bronchial responsiveness or lung function between groups. In patients treated with BDP compared with placebo, there was a significant reduction in toluidine blue-staining mast cells (p = 0.028) and total (p = 0.005) and activated eosinophils (p = 0.05) in biopsies but no difference in eosinophils or eosinophil cationic protein in BAL. Granulocyte-macrophage colony-stimulating factor expression was significantly reduced in the bronchial epithelium, and the thickness of Type III collagen deposition in the bronchial lamina reticularis reduced from 29.7 +/- 4.4 to 19.8 +/- 3.4 microns (mean +/- 95% confidence interval) (p = 0.04). No change in helper or activated helper T cells occurred. Prolonged BDP treatment reduces inflammatory infiltration, proinflammatory cytokine expression, and subepithelial collagen deposition, a recognized abnormality in asthma.

    Title Preembolization Functional Evaluation in Brain Arteriovenous Malformations: the Superselective Amytal Test.
    Date June 1992
    Journal Ajnr. American Journal of Neuroradiology

    PURPOSE: To describe our experience with the use of Amytal injected through a superselective catheter prior to planned embolization of cerebral arteriovenous malformations. MATERIALS AND METHODS: 109 superselective tests were performed with 30-mg injections of Amytal. All patients were evaluated by both clinical examination and EEG. RESULTS: Twenty-three of these tests were positive. There were no prolonged neurologic complications of the Amytal test. We also examined the value of EEG monitoring compared to clinical monitoring during the Amytal test. Of the 23 positive Amytal tests, only 12 showed a change on clinical exam (52%). This meant that almost half of the positive Amytal tests would have been falsely called negative (false negative rate of 10%). There were also three positive Amytal tests with changes on clinical examination without any change on EEG. CONCLUSION: The superselective Amytal test can be done safely as part of the interventional neuroradiologic procedure. Clinical and EEG monitoring of the patient are essential.

    Title Preembolization Functional Evaluation in Brain Arteriovenous Malformations: the Ability of Superselective Amytal Test to Predict Neurologic Dysfunction Before Embolization.
    Date June 1992
    Journal Ajnr. American Journal of Neuroradiology

    PURPOSE: To describe the incidence of neurologic dysfunction following embolization of supratentorial AVMs, and to correlate findings with results of preembolization Amytal tests. MATERIALS AND METHODS: Data from 147 embolizations of supratentorial AVMs following Amytal tests in 30 awake patients were analyzed retrospectively. RESULTS: Of five embolizations done after a positive Amytal test, two were followed by neurologic complications. Eighty-two embolizations done as single embolizations immediately after a negative Amytal test were associated with no neurologic complications. The remaining embolizations were parts of multiple series of embolizations, each beginning with an Amytal test and followed by a number of embolizations without catheter movement or repeat Amytal testing. Since any prior embolization in the series might reduce the sump effect of the AVM, embolic agent delivered later in the series could potentially reach functional brain tissue not fully tested by the Amytal test. Therefore, repeat embolizations (not immediately preceded by an Amytal test) were considered separately. In 60 repeat embolizations, six (10%) were associated with some neurologic complication. CONCLUSIONS: Repeat Amytal testing might detect the loss of sump effect as the AVM is embolized. We conclude that use of data from superselective Amytal tests adds to the safety of AVM embolizations and that repeat Amytal testing potentially could be valuable when serial embolization of a vessel is planned.

    Title Granular Cell Tumor of a Digital Nerve.
    Date October 1991
    Journal Cancer

    Granular cell tumor is an infrequently encountered albeit not rare neoplasm considered to be of neuroectodermal origin. An example of a benign granular cell tumor originating within a digital nerve is presented. The authors employed routine light microscopic techniques and immunostaining which demonstrate features of the granular cells reflecting structural and functional characteristics of Schwann's cells and support neuroectodermal derivation. Granular cell tumor is ubiquitous in location but occurs more frequently in tongue, skin and subcutaneous tissue. Clinical features are not specific, and a histologic evaluation is required for diagnosis. Circumscription and lack of cellular pleomorphism define a benign process. However, irrespective of its histologic appearance, the biologic potential is uncertain. Complete excision suffices as treatment for benign tumors.

    Title Eeg Monitoring in Carotid Endarterectomy.
    Date February 1991
    Journal Archives of Surgery (chicago, Ill. : 1960)
    Title Computerized Electroencephalography in the Evaluation of Early Dementia.
    Date September 1990
    Journal Brain Topography

    In elderly patients presenting to an ambulatory practice with complaints of cognitive disturbance, early dementia must be differentiated from depression. The present paper describes the application of standard electroencephalography and evoked potential testing (EEG/EP) and computerized electroencephalography with evoked potential mapping (CEEG/EPM) in the analysis of 64 elderly patients complaining of cognitive disturbance. Although previous reports have claimed a sensitivity level of up to 80% for EEG in demented patients, it appears that a lower sensitivity (37% for EEG alone and 61% for EEG/EP) may be expected at the time of early presentation according to the present study. No EEG/EP abnormalities were detected in patients with depression. In demented patients, CEEG/EPM was abnormal in 85% (46 of 54) of cases compared to 10% (1 of 10) of cases with depression. Specific information was obtained from EEG/EP studies that helped differentiate the various causes of dementia in three cases. In CEEG/EPM studies, a pattern of relative suppression of alpha activity or suppressed auditory P300 amplitude in the posterior parietal regions was observed in 11 or 23 (48%) patients with Alzheimer's disease and 2 of 31 (6%) patients with other forms of dementia. None of the depressed patients demonstrated such changes. Based on the present study, it appears that computerized techniques may hold promise as an adjunct to standard EEG evaluation of patients with mild cognitive change in whom diagnosis of dementia or depression is in doubt. Although standard EEG rarely demonstrates characteristic changes that may help differentiate causes of dementia, CEEG/EPM appears to demonstrate, on occasion, abnormalities in the posterior temporal and parietal regions in patients with a diagnosis of probable Alzheimer's disease and rarely in other forms of dementia or depression.

    Title Ischemic Brain Rescue by Transvenous Perfusion in Baboons with Venous Sinus Occlusion.
    Date March 1990
    Journal Stroke; a Journal of Cerebral Circulation

    We studied brain retroperfusion in nine adult baboons. Experiments in four baboons determined techniques and the safety of retroperfusion, and experiments in three baboons determined the ability of retroperfusion to reverse cerebral ischemia. Two baboons died before retroperfusion. Arterial blood was continuously circulated by an external pumping system from one femoral artery into the intracranial sinuses through specially designed balloon-tipped catheters placed percutaneously into the sigmoid sinuses bilaterally. The balloons intermittently occluded the sinuses. Ischemia was produced by occluding the left middle cerebral artery. Standard and computed electroencephalography with topographic mapping monitored the onset and reversal of ischemia. Retroperfusion rate exceeded 50 ml/min with a mean intrasinus pressure increase of 27 (0-149) mm Hg in all seven experiments. Venograms demonstrated complete or partial filling of the superior sagittal sinus in each experiment. Four experiments without ischemia established maximal balloon occlusion cycles, retroperfusion rates, and sinus pressure changes. These four baboons were neurologically normal after retroperfusion; two had normal magnetic resonance imaging scans. Ischemic changes, detected by electroencephalography following middle cerebral artery occlusion, were reversed with retroperfusion in all three ischemia experiments. Autopsies in the seven baboons demonstrated no parenchymal hemorrhage or edema. Our results suggest that further investigation of retroperfusion, and possibly retroinfusion of agents for cerebral protection, is warranted.

    Title Seizures and Hemiparesis in a Young Woman 24 Years After Treatment of Astrocytoma.
    Date July 1989
    Journal The Western Journal of Medicine

    An edited transcript of Neurology Grand Rounds held at the University of California, Los Angeles, Medical Center on January 27, 1988. John Mazziotta, MD, PhD, Professor of Neurology and Radiology, is the coordinator of these conferences. This conference was edited by Harry V. Vinters, MD.

    Title Computed Electroencephalographic Topographic Brain Mapping. A New and Accurate Monitor of Cerebral Circulation and Function for Patients Having Carotid Endarterectomy.
    Date October 1988
    Journal Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter

    To determine the usefulness of computed electroencephalographic (EEG) topographic (CET) brain mapping to monitor neurologic function during carotid endarterectomy (CEA), 46 consecutive patients having CEA were monitored preoperatively, intraoperatively, and immediately postoperatively by CET brain mapping and simultaneous 16-lead EEG. Preoperative studies revealed that 7 of 16 asymptomatic patients, 5 of 11 patients with amaurosis fugax, and 8 of 12 patients with transient ischemic attacks (TIAs) had abnormal CET brain mapping suggestive of previous subclinical stroke. EEG was abnormal in only 8 of the 20 patients with abnormal CET brain mapping. Intraoperatively during carotid cross-clamping, ischemic changes were seen on CET brain mapping in 23 patients whereas EEG detected these changes in only 13 patients. Ischemic changes detected by intraoperative CET brain mapping were more likely to occur in patients with previous stroke (six of seven) than in patients without previous stroke (17 of 39), p less than 0.05. Patients with changes detected by intraoperative CET brain mapping had an average carotid back-pressure of 38 mm Hg, in contrast to 57 mm Hg for patients without CET brain mapping changes, p less than 0.05. After endarterectomy, CET brain mapping revealed new ischemic changes in one patient who awoke with a mild stroke and in one patient who had TIAs and amaurosis fugax within 6 hours of surgery. We conclude that CET brain mapping is a sensitive, accurate, and useful noninvasive monitor of cerebral circulation and function for patients having CEA.(ABSTRACT TRUNCATED AT 250 WORDS)

    Title Autonomic Activity in the Carpal Tunnel Syndrome.
    Date September 1988
    Journal Orthopaedic Review

    The authors report the results of autonomic testing in patients with the carpal tunnel syndrome. Galvanic skin response (GSR) and skin temperature measurements in 46 patients and 32 normal controls were recorded and were statistically analyzed by computer. The findings were then correlated with the results of nerve conduction studies and duration of symptoms. Definite sympathetic changes were documented by a temperature increase in the affected index fingers of patients. These changes occurred in six patients who had symptoms for less than six months as well as in patients who had symptoms for more than six months. Nerve conduction studies were positive in 48% of patients with symptoms for less than six months and in 80% of patients with symptoms for six months or longer. There was no statistical difference between galvanic skin response measurements in the patients and the controls.

    Title The Centrifugal Effect and Other Spatial Artifacts of Topographic Eeg Mapping.
    Date January 1988
    Journal Journal of Clinical Neurophysiology : Official Publication of the American Electroencephalographic Society

    Topographic maps of EEG can contain artifacts that are foreign to clinical electroencephalographers trained to read traditional EEG records. Several spatial artifacts are described and discussed here, including the centrifugal effect, ring enhancement, spatial aliasing, electrode hills and holes, color-step effects, and restriction of minima/maxima to electrode sites. Users of quantitated EEG with topographic maps should be aware of these artifacts and should have a high suspicion for other analogous artifactual spatial phenomena when interpreting individual patient records.

    Title The Etiology of Valgus Angulation After Metaphyseal Fractures of the Tibia in Children.
    Date September 1987
    Journal Journal of Pediatric Orthopedics

    We conducted a retrospective study of proximal metaphyseal fractures of the tibia in children who developed valgus deformities. We reviewed the cases in an effort to determine the most likely etiology of post-fracture tibia valga, which occurs despite careful treatment and follow-up. We reviewed seven major theories presented in the literature regarding the etiology of this problem. Our conclusion was that all the theories were not prerequisites for the development of valgus angulation, but rather may be secondary mechanisms. We suggest that the most likely primary mechanism is an increased vascular response causing an asymmetric growth stimulation of the medial metaphysis of the proximal tibia.

    Title Evaluation of Stroke Using Eeg Frequency Analysis and Topographic Mapping.
    Date July 1987
    Journal Neurology

    Frequency analysis and topographic mapping of EEG were studied in 20 consecutive patients with mild stroke and in 20 age-matched normal subjects. Abnormally large increases in delta and decreases in alpha activity were seen over the scalp in 17 of 20 patients and in no normal subjects. Theta was unreliable by itself. The scalp area so localized appeared correct in each case compared with signs, symptoms, and neuroimaging studies. These computerized EEG analysis techniques were abnormal significantly more often than routine EEGs. The results obtained here with simple techniques agree with past studies done with more complex types of EEG analysis.

    Title The Angiocatheter in the Management of Hand Injuries.
    Date July 1986
    Journal The Journal of Hand Surgery
    Title Rapid Reduction of Off-task Behavior in Retarded Children by Use of Light-out.
    Date July 1985
    Journal Psychological Reports
    Title An Unusual Late Complication of Acrylic Spinal Fusion: Case Report.
    Date December 1983
    Journal Neurosurgery

    The authors report an unusual complication after posterior cervical spine fusion utilizing methyl methacrylate and metallic pins. Eight months postoperatively, the patient noticed a subcutaneous foreign body in the right side of the neck. Radiographic and operative findings confirmed the clinical impression of migration of one of the metallic pins.

    Title The Measurement of Children's Self-concepts As Related to Racial Membership.
    Date June 1972
    Journal Child Development

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