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1.  Autonomic complaints in patients with Restless Leg Syndrome 
Sleep medicine  2013;14(12):1413-1416.
Data regarding autonomic function in restless legs syndrome (RLS) is limited to heart rate and blood pressure changes in cases having periodic limb movements (PLMS).
We compared autonomic symptoms of 49 subjects with RLS vs. 291 Controls using the SCOPA-Autonomic questionnaire (23 items in six domains scored 0–3). The total score and domain scores were transformed to 0 to 100 points. Subjects with neurodegenerative disorders (i.e. dementia, parkinsonism) were excluded.
The RLS group was younger (mean±SD 77.9 ± 8.0 vs. 80.5 ± 7.9 yrs, p=.03) and had more women (84% vs. 69%, p=.04). The mean SCOPA-Aut Total score was higher in the RLS group compared with Controls (20 ± 11 vs. 16 ± 9, p= .005). Additionally the RLS group had abnormalities in GI, cardiovascular, and pupillomotor domains. When comparing the percentage of subjects with any complaint on individual questions (score of ≥ 1) the RLS group had a greater number of subjects with sialorrhea, constipation, early abdominal fullness, lightheadedness when standing, and heat intolerance.
Autonomic complaints, especially GI, cardiovascular, and oversensitivity to light, are significantly increased in subjects with RLS. Causes for autonomic dysfunction in RLS require further investigation.
PMCID: PMC4105217  PMID: 24152795
Restless Leg Syndrome; Autonomic symptoms
2.  Autonomic function, as self-reported on the SCOPA-autonomic questionnaire, is normal in essential tremor but not in Parkinson’s disease 
Parkinsonism & related disorders  2012;18(10):1089-1093.
To compare autonomic function of subjects with Parkinson’s disease (PD) and essential tremor (ET) relative to controls.
It has been reported that patients with PD have autonomic dysfunction while no literature exists regarding autonomic function in ET.
Subjects with PD, ET, and controls had autonomic function measured using the SCOPA-Autonomic questionnaire, with the total and domain scores transformed to a scale of 0–100 points.
62 subjects with PD, 84 with ET, and 291 controls were included. Women were more prevalent in control (69%) compared to PD (44%) and ET (44%) groups, and mean age was significantly younger in PD (73 yrs) and older in ET (83) compared to controls (81). The mean SCOPA-Aut Total score in PD was significantly higher than controls, with no difference in ET. No autonomic dysfunction was found in any domain in ET but in PD there were significant abnormalities in gastrointestinal, cardiovascular, urinary, and thermoregulatory domains. Individual question data revealed a significantly higher percentage of subjects with dysfunction on 11/23 questions in the PD group but only 1 question (sialorrhea) in the ET group compared with controls.
Autonomic scores, particularly gastrointestinal, cardiovascular, urinary, and thermoregulatory were increased in patients with PD, as assessed by SCOPA-Aut. Patients with ET did not exhibit autonomic dysfunction, with the exception of sialorrhea.
PMCID: PMC3665503  PMID: 22771283
Autonomic dysfunction; Parkinson’s disease; Essential tremor
3.  A Double-Blind Randomized Controlled Trial of Continuous Intravenous Ketorolac vs Placebo for Adjuvant Pain Control After Renal Surgery 
Mayo Clinic Proceedings  2012;87(11):1089-1097.
To evaluate the efficacy and safety of a novel, continuous intravenous infusion of ketorolac, a powerful nonopioid analgesic, for postoperative pain control.
Patients and Methods
A prospective, double-blind, randomized, placebo-controlled trial of a continuous infusion of ketorolac tromethamine in 1 L of normal saline vs placebo was performed in 135 patients aged 18 to 75 years after laparoscopic donor nephrectomy or percutaneous nephrolithotomy completed from October 7, 2008, through July 21, 2010. Primary study end points were the 24-hour differences in visual analog pain scores and total narcotic consumption, whereas secondary end points were differences in urine output, serum creatinine level, and hemoglobin level.
The study was stopped after randomization of 135 patients (68 in the ketorolac group and 67 in the placebo group) when interim analysis indicated that the difference in mean pain scores between the 2 groups (difference, 0.6) was smaller than the 1-point threshold set forth in the power calculations. No statistically significant change was noted in hemoglobin levels from preoperative to postoperative values (P=.13) or in postoperative serum creatinine levels (P=.13).
Although continuous infusion of ketorolac produced only a modest decrease in the use of narcotics, it appears to offer a safe therapeutic option for nonnarcotic pain control.
Trial Registration Identifiers: NCT00765128 and NCT00765232
PMCID: PMC3532697  PMID: 23058854
LDN, laparoscopic donor nephrectomy; NSAID, nonsteroidal anti-inflammatory drug; PNL, percutaneous nephrolithotomy; VAS, visual analog scale
4.  Incidental Lewy Body Disease: Electrophysiological Findings Suggesting Pre-clinical Lewy Body Disorders 
Evaluate electrophysiologic findings in incidental Lewy Body disease (ILBD).
ILBD, Control, and Parkinson's disease (PD) subjects had electrophysiological evaluation within two years prior to autopsy. Data analyzed included surface electromyography (EMG) of upper extremity muscles during rest and muscle activation, and electroencephalography (EEG) recording at rest. For EMG, gross tracings and spectral peaks were analyzed. EEG measures analyzed were background frequency and power in delta, theta, alpha, and beta bands.
Three of ten ILBD subjects (30%) showed unilateral rhythmic EMG discharges at rest without a visually apparent rest tremor. The ILBD resting EMG frequency was lower than in the Control group with no overlap (P=0.03) and close to that of the PD group. The ILBD group had significantly lower background rhythm frequency than the Control group (P=0.001) but was greater than the PD group (P=0.01).
The electrophysiologic changes in ILBD cases are between those of Control and PD, suggesting that these findings may reflect changes correlating with ILBD as a possible precursor to PD.
Electrophysiologic changes in ILBD may assist with the identification of a preclinical stage for Lewy body disorders and help the development of a therapeutic agent for modifying Lewy body disease progression.
PMCID: PMC3164932  PMID: 21616709
Lewy body; Electromyography; Electroencephalography; Pathology; Parkinson's disease; Tremor
5.  Probable RBD is Increased in Parkinson’s Disease But Not in Essential Tremor or Restless Legs Syndrome 
Parkinsonism & related disorders  2011;17(6):456-458.
Compare the frequency of REM sleep behavior disorder (RBD) and excessive daytime sleepiness (EDS) in Parkinson’s disease (PD), restless legs syndrome (RLS), essential tremor (ET), and control subjects.
Subjects enrolled in a longitudinal clinicopathologic study, and when available an informant, completed the Mayo Sleep Questionnaire, which asks “Have you ever been told that you act out your dreams?”, and the Epworth Sleepiness Scale (ESS).
Probable RBD (based on informant response to the questionnaire) was much more frequent in PD (34/49, 69%, p<0.001) than in RLS (6/30, 20%), ET (7/53, 13%), or control subjects (23/175, 13%), with an odds ratio of 11 for PD compared to controls. The mean ESS and the number of subjects with an ESS ≥ 10 was higher in PD (29/60, 48%, p<0.001) and RLS (12/39, 31%, p<0.001) compared with ET (12/93, 13%) and Controls (34/296, 11%).
Probable RBD is much more frequent in PD with no evidence to suggest an increase in either RLS or ET. Given the evidence that RBD is a synucleinopathy, the lack of an increased frequency of RBD in subjects with ET or RLS suggests the majority of ET and RLS subjects are unlikely to be at increased risk for developing PD.
PMCID: PMC3119772  PMID: 21482171
Parkinson’s disease; REM sleep behavior disorder; essential tremor; restless legs syndrome; excessive daytime sleepiness
6.  Parkinson’s Disease, Cortical Dysfunction, and Alpha-Synuclein 
The ability to understand how Parkinson’s disease (PD) neurodegeneration leads to cortical dysfunction will be critical for developing therapeutic advances in PD dementia (PD-D). The overall purpose of this project was to study the small amplitude cortical myoclonus in PD as an in vivo model of focal cortical dysfunction secondary to PD neurodegeneration. The objectives were to test the hypothesis that cortical myoclonus in PD is linked to abnormal levels of α-synuclein in primary motor cortex and to define its relationship to various biochemical, clinical, and pathological measures.
Primary motor cortex was evaluated for 11 PD subjects with (PD+Myoclonus group) and 8 without (PD group) electrophysiologically confirmed cortical myoclonus who had premortem movement and cognitive testing. Similarly assessed 9 controls were used for comparison. Measurements for α-synuclein, Aβ-42 peptide, and other biochemical measures were made in primary motor cortex.
A 36% increase in α-synuclein was found in the motor cortex of PD+Myoclonus cases when compared to PD without myoclonus. This occurred without significant differences in insoluble α-synuclein, phosphorylated to total α-synuclein ratio, or Aβ-42 peptide levels. Higher total motor cortex α-synuclein levels significantly correlated with the presence of cortical myoclonus but did not correlate with multiple clinical or pathological findings.
These results suggest an association between elevated α-synuclein and the dysfunctional physiology arising from the motor cortex in PD+Myoclonus cases. Alzheimer’s disease pathology was not associated with cortical myoclonus in PD. Cortical myoclonus arising from motor cortex is a model to study cortical dysfunction in PD.
PMCID: PMC3154995  PMID: 21542019
7.  Neuropathological Findings of PSP in the Elderly Without Clinical PSP: Possible Incidental PSP? 
Parkinsonism & related disorders  2011;17(5):365-371.
We aimed to describe cases with incidental neuropathological findings of progressive supranuclear palsy (PSP) from the Banner Sun Health Research Institute Brain and Body Donation Program.
We performed a retrospective review of 277 subjects with longitudinal motor and neuropsychological assessments who came to autopsy. The mean Gallyas-positive PSP features grading for subjects with possible incidental neuropathological PSP was compared to those of subjects with clinically manifest disease.
There were 5 cases with histopathological findings suggestive of PSP, but no parkinsonism, dementia or movement disorder during life. Cognitive evaluation revealed 4 of the 5 cases to be cognitively normal; one case had amnestic mild cognitive impairment (MCI) in her last year of life. The mean age at death of the 5 cases was 88.9 years (range 80-94). All 5 individuals had histopathologic microscopic findings suggestive of PSP. Mean Gallyas-positive PSP features grading was significantly lower in subjects with possible incidental neuropathological PSP than subjects with clinical PSP, particularly in the subthalamic nucleus.
We present 5 patients with histopathological findings suggestive of PSP, without clinical PSP, dementia or parkinsonism during life. These incidental neuropathological PSP findings may represent the early or pre-symptomatic stage of PSP. The mean Gallyas-positive PSP features grading was significantly lower in possible incidental PSP than in clinical PSP, thus suggesting that a threshold of pathological burden needs to be reached within the typically affected areas in PSP before clinical signs and symptoms appear.
PMCID: PMC3109165  PMID: 21420891
progressive supranuclear palsy; PSP; incidental; autopsy; parkinsonism; neuropathology
9.  Incidental Lewy Body Disease: Clinical Comparison to a Control Cohort 
Limited clinical information has been published on cases pathologically diagnosed with incidental Lewy body disease (ILBD). Standardized, longitudinal movement and cognitive data was collected on a cohort of subjects enrolled in the Sun Health Research Institute Brain and Body Donation Program. Of 277 autopsied subjects who had antemortem clinical evaluations within the previous 3 years, 76 did not have Parkinson’s disease, a related disorder, or dementia of which 15 (20%) had ILBD. Minor extrapyramidal signs were common in subjects with and without ILBD. Cognitive testing revealed an abnormality in the ILBD group in the Trails B test only. ILBD cases had olfactory dysfunction; however, sample size was very small. This preliminary report revealed ILBD cases have movement and cognitive findings that for the most part were not out of proportion to similarly assessed and age-similar cases without Lewy bodies. Larger sample size is needed to have the power to better assess group differences.
PMCID: PMC2935627  PMID: 20175211
incidental Lewy body disease; Lewy bodies; Parkinson’s disease; demential with Lewy bodies
10.  Serologic testing for symptomatic coccidioidomycosis in immunocompetent and immunosuppressed hosts 
Mycopathologia  2006;162(5):317-324.
Serologic studies are an important diagnostic tool in the clinical evaluation and follow-up of persons with coccidioidomycosis. Numerous types of serologic tests are available, including immunodiffusion, enzyme immunoassay, and complement fixation. We conducted a retrospective review of the results of 1,797 serologic tests spanning 12 months from the onset of coccidioidomycosis in 298 immunocompetent and 62 immunosuppressed persons with symptomatic infection. Using the onset of symptoms as a reference point, we plotted the positive or negative serologic results over time for both groups. Compared with the immunocompetent group, immunosuppressed persons had lower rates of seropositivity for every type of test during the first year after onset of symptoms for coccidioidomycosis, although many results did not achieve statistical significance. Combining the results of these tests increased the sensitivity of the serologic evaluation in immunocompromised patients. Immunosuppressed persons have the ability to mount a serologic response to coccidioidomycosis, but in some circumstances, multiple methods may be required to improve detection.
PMCID: PMC2780641  PMID: 17123029
coccidioidomycosis; complement fixation; enzyme immunoassay; immunocompetence; immunodiffusion; immunosuppression
11.  Restoration of Femoral Anatomy in TKA With Unisex and Gender-specific Components 
Recent modifications in total knee prosthesis design theoretically better accommodate the anatomy of the female femur and thereby have the theoretical potential to improve clinical results in TKA by more accurately restoring femoral posterior condylar offset, reducing femoral notching, reducing femoral component flexion, and reducing component overhang. First, we radiographically evaluated whether a contemporary unisex prosthesis would accommodate female anatomy equally as well as male anatomy. Next, we radiographically evaluated female knees in which a gender-specific prosthesis was used. Pre- and postoperative radiographs of 122 knees (42 female unisex, 41 male unisex, 39 female gender-specific) were reviewed. In the unisex groups, there were no differences in femoral notching or femoral component flexion. Posterior femoral offset increased in both groups. However, femoral component overhang was worse in female knees (17%) than in male knees (0%). In the gender-specific female group, the incidence of component overhang was similar to that in the unisex female group. Unisex femoral components of this specific design do not equally match the native anatomy male and female knees. In some women, a compromise was required in sizing.
PMCID: PMC2565022  PMID: 18719972
12.  Identification of Stroke Mimics in the Emergency Department Setting 
Journal of Brain Disease  2009;1:19-22.
Background and Purpose
Previous studies have shown a stroke mimic rate of 9%–31%. We aimed to establish the proportion of stroke mimics amongst suspected acute strokes, to clarify the aetiology of stroke mimic and to develop a prediction model to identify stroke mimics.
This was a retrospective cohort observational study. Consecutive “stroke alert” patients were identified over nine months in a primary stroke centre. 31 variables were collected. Final diagnosis was defined as “stroke” or “stroke mimic”. Multivariable regression analysis was used to define clinical predictors of stroke mimic.
206 patients were reviewed. 22% were classified as stroke mimics. Multivariable scoring did not help in identification of stroke mimics. 99.5% of patients had a neurological diagnosis at final diagnosis.
22% of patients with suspected acute stroke had a stroke mimic. The aetiology of stroke mimics was varied, with seizure, encephalopathy, syncope and migraine being commonest. Multivariable scoring for identification of stroke mimics is not feasible. 99.5% of patients had a neurological diagnosis. This strengthens the case for the involvement of stroke neurologists/stroke physicians in acute stroke care.
PMCID: PMC3676321  PMID: 23818805
stroke; transient ischemic attack; stroke mimic
13.  The MUC1 Cytoplasmic Tail and Tandem Repeat Domains Contribute to Mammary Oncogenesis in FVB Mice 
Though the importance of the transmembrane mucin MUC1 in mammary oncogenesis has long been recognized, the relative contributions of the cytoplasmic tail and tandem repeat domains are poorly understood.
To address this, mouse models of mammary carcinogenesis were created expressing full-length, cytoplasmic tail-deleted, or tandem repeat-deleted MUC1 constructs.
Overexpression of full-length MUC1 resulted in tumor formation in young mice (≤12 months); however, loss of either the cytoplasmic tail or the tandem repeat domain abrogated this oncogenic capacity. Aged mice in all strains developed late-onset mammary tumors similar to those previously described for the FVB background.
This study is the first spontaneous cancer model to address the relative importance of the cytoplasmic tail and tandem repeat domains to MUC1-driven mammary oncogenesis, and suggests that both of these domains are essential for tumor formation.
PMCID: PMC3091404  PMID: 21655373
MUC1; breast cancer; mouse models; cytoplasmic tail; tandem repeat; mucin

Results 1-13 (13)