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1.  Pathophysiology of primary spinal syringomyelia 
Journal of neurosurgery. Spine  2012;17(5):367-380.
The pathogenesis of syringomyelia in patients with an associated spinal lesion is incompletely understood. The authors hypothesized that in primary spinal syringomyelia, a subarachnoid block effectively shortens the length of the spinal subarachnoid space (SAS), reducing compliance and the ability of the spinal theca to dampen the subarachnoid CSF pressure waves produced by brain expansion during cardiac systole. This creates exaggerated spinal subarachnoid pressure waves during every heartbeat that act on the spinal cord above the block to drive CSF into the spinal cord and create a syrinx. After a syrinx is formed, enlarged subarachnoid pressure waves compress the external surface of the spinal cord, propel the syrinx fluid, and promote syrinx progression.
To elucidate the pathophysiology, the authors prospectively studied 36 adult patients with spinal lesions obstructing the spinal SAS. Testing before surgery included clinical examination; evaluation of anatomy on T1-weighted MRI; measurement of lumbar and cervical subarachnoid mean and pulse pressures at rest, during Valsalva maneuver, during jugular compression, and after removal of CSF (CSF compliance measurement); and evaluation with CT myelography. During surgery, pressure measurements from the SAS above the level of the lesion and the lumbar intrathecal space below the lesion were obtained, and cardiac-gated ultrasonography was performed. One week after surgery, CT myelography was repeated. Three months after surgery, clinical examination, T1-weighted MRI, and CSF pressure recordings (cervical and lumbar) were repeated. Clinical examination and MRI studies were repeated annually thereafter. Findings in patients were compared with those obtained in a group of 18 healthy individuals who had already undergone T1-weighted MRI, cine MRI, and cervical and lumbar subarachnoid pressure testing.
In syringomyelia patients compared with healthy volunteers, cervical subarachnoid pulse pressure was increased (2.7 ± 1.2 vs 1.6 ± 0.6 mm Hg, respectively; p = 0.004), pressure transmission to the thecal sac below the block was reduced, and spinal CSF compliance was decreased. Intraoperative ultrasonography confirmed that pulse pressure waves compressed the outer surface of the spinal cord superior to regions of obstruction of the subarachnoid space.
These findings are consistent with the theory that a spinal subarachnoid block increases spinal subarachnoid pulse pressure above the block, producing a pressure differential across the obstructed segment of the SAS, which results in syrinx formation and progression. These findings are similar to the results of the authors' previous studies that examined the pathophysiology of syringomyelia associated with obstruction of the SAS at the foramen magnum in the Chiari Type I malformation and indicate that a common mechanism, rather than different, separate mechanisms, underlies syrinx formation in these two entities. Clinical trial registration no.: NCT00011245. (
PMCID: PMC3787878  PMID: 22958075
syringomyelia; physiology; ultrasonography; surgery; cerebrospinal fluid; magnetic resonance imaging; myelography
3.  A Randomized Add-on Trial of an N-methyl-d-aspartate Antagonist in Treatment-Resistant Bipolar Depression 
Archives of general psychiatry  2010;67(8):793-802.
Existing therapies for bipolar depression have a considerable lag of onset of action. Pharmacological strategies that produce rapid antidepressant effects—for instance, within a few hours or days—would have an enormous impact on patient care and public health.
To determine whether an N-methyl-d-aspartate–receptor antagonist produces rapid antidepressant effects in subjects with bipolar depression.
A randomized, placebo-controlled, double-blind, crossover, add-on study conducted from October 2006 to June 2009.
Mood Disorders Research Unit at the National Institute of Mental Health, Bethesda, Maryland.
Eighteen subjects with DSM-IV bipolar depression (treatment-resistant).
Subjects maintained at therapeutic levels of lithium or valproate received an intravenous infusion of either ketamine hydrochloride (0.5 mg/kg) or placebo on 2 test days 2 weeks apart. The Montgomery-Asberg Depression Rating Scale was used to rate subjects at baseline and at 40, 80, 110, and 230 minutes and on days 1, 2, 3, 7, 10, and 14 postinfusion.
Main Outcome Measures
Change in Montgomery-Asberg Depression Rating Scale primary efficacy measure scores.
Within 40 minutes, depressive symptoms significantly improved in subjects receiving ketamine compared with placebo (d=0.52, 95% confidence interval [CI], 0.28-0.76); this improvement remained significant through day 3. The drug difference effect size was largest at day 2 (d=0.80, 95% CI, 0.55-1.04). Seventy-one percent of subjects responded to ketamine and 6% responded to placebo at some point during the trial. One subject receiving ketamine and 1 receiving placebo developed manic symptoms. Ketamine was generally well tolerated; the most common adverse effect was dissociative symptoms, only at the 40-minute point.
In patients with treatment-resistant bipolar depression, robust and rapid antidepressant effects resulted from a single intravenous dose of an N-methyl-d-aspartate antagonist.
Trial Registration Identifier: NCT00088699
PMCID: PMC3000408  PMID: 20679587
Magnetic resonance imaging (MRI) provides superior visualization of the prostate and surrounding anatomy, making it the modality of choice for imaging the prostate gland. This pilot study was performed to determine the feasibility and dosimetric quality achieved when placing high-dose-rate prostate brachytherapy catheters under MRI guidance in a standard “closed-bore” 1.5T scanner.
Methods and Materials:
Patients with intermediate-risk and high-risk localized prostate cancer received MRI-guided high-dose-rate brachytherapy boosts before and after a course of external beam radiotherapy. Using a custom visualization and targeting program, the brachytherapy catheters were placed and adjusted under MRI guidance until satisfactory implant geometry was achieved. Inverse treatment planning was performed using high-resolution T2-weighted MRI.
Ten brachytherapy procedures were performed on 5 patients. The median percentage of volume receiving 100% of prescribed minimal peripheral dose (V100) achieved was 94% (mean, 92%; 95% confidence interval, 89–95%). The urethral V125 ranged from 0% to 18% (median, 5%), and the rectal V75 ranged from 0% to 3.1% (median, 0.3%). In all cases, lesions highly suspicious for malignancy could be visualized on the procedural MRI, and extracapsular disease was identified in 2 patients.
High-dose-rate prostate brachytherapy in a standard 1.5T MRI scanner is feasible and achieves favorable dosimetry within a reasonable period with high-quality image guidance. Although the procedure was well tolerated in the acute setting, additional follow-up is required to determine the long-term safety and efficacy of this approach.
PMCID: PMC2396328  PMID: 15275727
Prostate cancer; Brachytherapy; MRI; Image guidance
5.  A Combined Approach to Women’s Health Is Associated With a Greater Likelihood of Repeat Mammography in a Population of Financially Disadvantaged Women 
Preventing Chronic Disease  2007;4(4):A89.
Integrating one or more public health programs may improve the ability of programs to achieve common goals. Expanding knowledge on how program integration occurs, how it benefits each individual program, and how it contributes to the achievement of common goals is an important area of inquiry in public health.
The National Breast and Cervical Cancer Early Detection Program (NBCCEDP) and the Well-Integrated Screening and Evaluation for Women Across the Nation (WISEWOMAN) program combined data from 10 of their overlapping state or tribal programs to calculate prevalence estimates of repeat mammography at 18 months. The data were stratified by whether women attended the combined program or only the NBCCEDP. Logistic regression analyses were conducted to identify factors that were thought to independently contribute to a greater likelihood of a woman receiving a repeat mammogram.
Women who participated in both programs were 1.5 to 5.1 times as likely to be rescreened, depending on program location, as women who participated only in the NBCCEDP. WISEWOMAN participants who received a follow-up WISEWOMAN screening for chronic disease risk factors within a year of their initial WISEWOMAN screening were 5 times more likely to return for a follow-up mammogram through the NBCCEDP than were WISEWOMAN participants who did not.
Participation in both the NBCCEDP and the WISEWOMAN program is associated with a greater likelihood of a woman returning for a follow-up mammogram within 18 months of her initial examination. Collecting more in-depth information on motivational factors and on the association between receipt of multiple services and a woman's engagement in a health program should be the subject of future research.
PMCID: PMC2099287  PMID: 17875264

Results 1-5 (5)