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Papers by Thomas Davis

Research paper thumbnail of Perceived Benefit of CACREP (2001) Core Curriculum Standards

Counselor Education and Supervision, Jun 1, 2004

... Jason M. McGlothlin, Counseling and Human Development Services, Kent State University;Thomas ... more ... Jason M. McGlothlin, Counseling and Human Development Services, Kent State University;Thomas E. Davis, Department of Counseling and Higher ... Loesch and Vacc (1994) found that counselors who took the NCE typically scored lowest on the questions pertaining to career ...

Research paper thumbnail of Perceived Expectations Related to Promotion and Tenure: A National Survey of CACREP Program Liaisons

Counselor Education and Supervision, Dec 1, 2006

The purpose of the present study was to determine the perceptions of expectations and practices t... more The purpose of the present study was to determine the perceptions of expectations and practices that contribute to decisions regarding promotion and tenure for counselor educators. Council for Accreditation of Counseling and Related Educational Programs liaisons for 74 counselor education programs responded to an Internet-based survey about perceptions of promotion and tenure practices in their programs and institutions. The responses indicate that relatively equal emphasis is placed on teaching, scholarship, and service. Implications for defining promotion and tenure criteria are discussed, and recommendations for further research are provided.

Research paper thumbnail of Dosage compensation proteins targeted to X chromosomes by a determinant of hermaphrodite fate

Science, 1999

rodite-specific sation) genes S~C (lo, (sex 11). and In dosage hermaphrodites, compen-Targeted to... more rodite-specific sation) genes S~C (lo, (sex 11). and In dosage hermaphrodites, compen-Targeted to X Chromosomes by these genes activate dosage compensation and the genetic pathway for hermaphrodite sexual development (12-15). Both SDC-2 a Determinant of and S D C~ are necessary for localization of

Research paper thumbnail of Deep brain stimulation may reduce the relative risk of clinically important worsening in early stage Parkinson's disease

Parkinsonism & related disorders, Jan 11, 2015

The Vanderbilt pilot trial of deep brain stimulation (DBS) in early Parkinson's disease (PD) ... more The Vanderbilt pilot trial of deep brain stimulation (DBS) in early Parkinson's disease (PD) enrolled patients on medications six months to four years without motor fluctuations or dyskinesias. We conducted a patient-centered analysis based on clinically important worsening of motor symptoms and complications of medical therapy for all subjects and a subset of subjects with a more focused medication duration. Continuous outcomes were also analyzed for this focused cohort. A post hoc analysis was conducted on all subjects from the pilot and a subset of subjects taking PD medications 1-4 years at enrollment. Clinically important worsening is defined as both a ≥ 3 point increase in UPDRS Part III and a ≥ 1 point increase in Part IV. DBS plus optimal drug therapy (DBS + ODT) subjects experienced a 50-80% reduction in the relative risk of worsening after two years. The DBS + ODT group was improved compared to optimal drug therapy (ODT) at each time point on Total UPDRS and Part III (...

Research paper thumbnail of Ventricular Width and Complicated Recovery following Deep Brain Stimulation Surgery

Stereotactic and Functional Neurosurgery, 2012

Candidates for deep brain stimulation (DBS) must be carefully evaluated to balance expected benef... more Candidates for deep brain stimulation (DBS) must be carefully evaluated to balance expected benefits with the possibility of serious complications. Several predictive factors exist but are imperfect. The aim of this study was to determine whether linear measurements of the lateral ventricles predict complications following DBS. We retrospectively studied a cohort of DBS patients. The primary outcome was postoperative confusion; secondary outcomes were discharge disposition and all in-hospital complications. For each case, a control matched for age, sex, diagnosis, and DBS target was identified. Linear measurements were made from routine preoperative axial MRIs for both cases and controls. A total of 40 patients met one or more of the end points. Patients with postoperative confusion had a significantly larger minimum width of the lateral ventricles than controls. Patients discharged to a higher level of care and those with any complications also had significantly greater maximum and minimum ventricular widths than controls. These results suggest that preoperative measurement of the maximum and minimum width of the lateral ventricles may help predict which patients are at risk for complicated recoveries following DBS.

Research paper thumbnail of Atypical junctional melanocytic proliferations in benign lichenoid keratosis

Human pathology, 2003

Melanocytic lesions with lichenoid regression may mimic a benign lichenoid keratosis (BLK) histol... more Melanocytic lesions with lichenoid regression may mimic a benign lichenoid keratosis (BLK) histologically. A total of 336 BLKs were reviewed and deeper sections obtained to determine the frequency of this phenomenon. Two cases (0.6%) showed at least 1 melanocytic nest or junctional multinucleated melanocyte (starburst melanocyte) on deeper sections confirmed by MART-1 immunostaining. Both of these cases demonstrated solar elastosis, and 1 case had an effaced rete ridge pattern. Not included in the histological study are 5 additional cases in which the initial slide showed only lichenoid dermatitis, but deeper sections obtained before to the initial sign-out revealed a melanocytic proliferation. These 5 cases would have been signed out as "consistent with BLK" if deeper sections had not been obtained. Fluorescent in situ hybridization (FISH) was performed on 3 cases; in each case, the melanocytes demonstrated a loss of chromosome 9p21 DNA copy number. The finding of nests o...

Research paper thumbnail of Neuropsychological effects of deep brain stimulation for Parkinson′s disease

Surgical Neurology International, 2013

Putative changes of cognition after deep brain stimulation (DBS) in patients with Parkinson&a... more Putative changes of cognition after deep brain stimulation (DBS) in patients with Parkinson's disease (PD) are a matter of debate. The aim of this study was to assess cognitive abilities before and following bilateral subthalamic nucleus (STN) DBS and to review the available literature. Twenty patients underwent bilateral DBS of the STN. Cognitive skills were assessed in a standardized fashion before and at least at 12 months after the surgical intervention. There was a significant decline of both semantic and phonematic verbal fluency and a mild trend for a deterioration of verbal memory after DBS. Mood, general cognitive screening, and visospatial abilities remained unchanged. STN DBS in the treatment of PD has resulted in a significant reduction of motor symptoms and improved independence and quality of life in appropriately selected patients. However, it may have isolatable effects on verbal fluency and related function. Case series in the literature reported similar findings. Potential candidates for DBS should be counseled about the risk of mild cognitive declines.

Research paper thumbnail of Deep brain stimulation in early Parkinson’s disease: Enrollment experience from a pilot trial

Parkinsonism & Related Disorders, 2012

Background-Deep brain stimulation (DBS) of the subthalamic nucleus is an accepted therapy for adv... more Background-Deep brain stimulation (DBS) of the subthalamic nucleus is an accepted therapy for advanced Parkinson's disease (PD). In animal models, pharmacologic ablation and stimulation of the subthalamic nucleus have resulted in clinical improvement and, in some cases, improved survival of dopaminergic neurons. DBS has not been studied in the early stages of PD, but early application should be explored to evaluate safety, efficacy, and the potential to alter disease progression.

Research paper thumbnail of Multiple system atrophy: new developments in pathophysiology and therapy

Parkinsonism & Related Disorders, 2001

There have been substantial advances in the last five years in understanding the basic and clinic... more There have been substantial advances in the last five years in understanding the basic and clinical pathophysiology underlying multiple system atrophy (MSA). Identification of glial cytoplasmic inclusions has been the most important organizing principle for further elucidation of underlying mechanisms. Recently, several unexpected developments at the clinical level have been reported. In this article, we will focus on two of

Research paper thumbnail of Familial essential tremor with apparent autosomal dominant inheritance: Should we also consider other inheritance modes?

Movement Disorders, 2006

A positive family history is present in many patients with essential tremor (ET), but twin studie... more A positive family history is present in many patients with essential tremor (ET), but twin studies and segregation analysis have suggested that ET is not entirely a genetic disorder. Two genetic loci have been identified in autosomal dominant (AD) ET and polymorphisms in the DRD3 and HS1-BP3 genes have been proposed as the possible susceptibility factors for ET. There is also evidence for further genetic heterogeneity. We evaluated 4 unrelated large kindreds with ET with an apparent AD mode of transmission. Each kindred spanned at least 3 generations and contained at least 13 living affected subjects who met criteria for definitive ET. None of the pedigrees had evidence for inheritance of ET from both parents. Known genetic ET loci were excluded in these families. We detected a preferential transmission of ET in every kindred and the proportion of affected offspring varied from 75% to 90% (P Ͻ 0.05) in the generations with complete ascertainment. Our data indicate that non-Mendelian preferential transmission of an affected allele is a feature in many ET kindreds with multiple affected members and an apparent AD mode of inheritance. ET may have a complex etiology. Additional genetic models need to be considered, including an interaction of susceptibility genes and environmental risk factors.

Research paper thumbnail of Treatment of parkinson's disease with the partial dopamine agonist EMD 49980

Movement Disorders, 1993

The motor effects of the partial dopamine agonist EMD 49980 were evaluated in parkinsonian patien... more The motor effects of the partial dopamine agonist EMD 49980 were evaluated in parkinsonian patients under controlled conditions. EMD 49980 monotherapy resulted in a mild improvement in parkinsonian symptoms, but when co-administered with levodopa, had no significant effect on dyskinesias or on the antiparkinsonian effect of the dopamine precursor. These results suggest that EMD 49980 exerts a net weak dopamine agonist effect but fails to ameliorate levodopa-induced dyskinesias.

Research paper thumbnail of Effect of aging and dopaminomimetic therapy on mitochondrial respiratory function in Parkinson's disease

Movement Disorders, 1992

Oxygen consumption and enzyme activity were evaluated in platelet mitochondria from 17 patients w... more Oxygen consumption and enzyme activity were evaluated in platelet mitochondria from 17 patients with Parkinson's disease. In comparison with age-matched controls, no consistent abnormality could be discerned in complex I, complex 11-111, or complex IV oxygen consumption, or in the enzyme activity of these respiratory chain complexes. Neither chronic therapy with levodopdcarbidopa alone nor in combination with deprenyl significantly affected any measure of mitochondrial respiratory function. There was no discernible relationship between patient age or disease severity and any parameter of mitochondrial respiration. Moreover, blood lactate levels following glucose loading were not different in patients and controls. These results fail to support the occurrence of a generalized defect in any mitochondrial respiratory function in Parkinson's disease.

Research paper thumbnail of Milacemide therapy for Parkinson's disease

Movement Disorders, 1993

The clinical effects of central glutamatergic stimulation by the glycine prodrug milacemide were ... more The clinical effects of central glutamatergic stimulation by the glycine prodrug milacemide were studied in six patients with Parkinson's disease under double-blind, placebo-controlled conditions. When administered as monotherapy at a single oral dose of 1,200 mg, the drug increased overall parkinsonian severity transiently, mostly due to an effect on rigidity. Milacemide did not, however, alter levodopa-induced dyskinesias. These results support the view that drugs acting on the glutamatergic system can influence motor function in patients with extrapyramidal movement disorders and that pharmaceutical agents that selectively block certain subtypes of glutamate receptors may ameliorate parkinsonian symptoms.

Research paper thumbnail of Botulinum toxin type A therapy during pregnancy

Movement Disorders, 2004

16. Kompoliti K. Estrogen and movement disorders. Clin Neuropharmacol 1999;22:318 -326. 17. Moris... more 16. Kompoliti K. Estrogen and movement disorders. Clin Neuropharmacol 1999;22:318 -326. 17. Morissette M., Paola DT. Effect of chronic estradiol and progesterone treatments of ovariectomized rats on brain dopamine uptake sites. J Neurochem 1993;60:1876 -1881. 18. Strijks E., Kremer MAJ, Horstink M. Effects of female sex steroids on Parkinson's disease in postmenopausal women. Clin Neuropharmacol 1999;22:93-97. 19. Cabrera RJ, Navarro CE. Progesterone in vitro increases NMDAevoked [3H] dopamine release from striatal slices in proestrus rats. Neuropharmacology 1996;35:175-178. 20. Nuwayhid SJ, Werling LL. Steroids modulate N-methyl-D-aspartate-stimulated [3H] dopamine release from rat striatum via sigma receptors. J Pharmacol Exp Ther 2003;306:934 -940. 21. Cabrera RJ, Bregonzio C, Lanconi M, Mampel A. Allopregnanolone increase in striatal N-methyl-D-aspartic acid evoked [3H] dopamine release is estrogen and progesterone dependent. Cell

Research paper thumbnail of Deep brain stimulation in early stage Parkinson's disease: operative experience from a prospective randomised clinical trial

Journal of Neurology, Neurosurgery & Psychiatry, 2012

Recent evidence suggests that deep brain stimulation of the subthalamic nucleus (STN-DBS) may hav... more Recent evidence suggests that deep brain stimulation of the subthalamic nucleus (STN-DBS) may have a disease modifying effect in early Parkinson's disease (PD). A randomised, prospective study is underway to determine whether STN-DBS in early PD is safe and tolerable. 15 of 30 early PD patients were randomised to receive STN-DBS implants in an institutional review board approved protocol. Operative technique, location of DBS leads and perioperative adverse events are reported. Active contact used for stimulation in these patients was compared with 47 advanced PD patients undergoing an identical procedure by the same surgeon. 14 of the 15 patients did not sustain any long term (>3 months) complications from the surgery. One subject suffered a stroke resulting in mild cognitive changes and slight right arm and face weakness. The average optimal contact used in symptomatic treatment of early PD patients was: anterior -1.1±1.7 mm, lateral 10.7±1.7 mm and superior -3.3±2.5 mm (anterior and posterior commissure coordinates). This location is statistically no different (0.77 mm, p>0.05) than the optimal contact used in the treatment of 47 advanced PD patients. The perioperative adverse events in this trial of subjects with early stage PD are comparable with those reported for STN-DBS in advanced PD. The active contact position used in early PD is not significantly different from that used in late stage disease. This is the first report of the operative experience from a randomised, surgical versus best medical therapy trial for the early treatment of PD.

Research paper thumbnail of Comparison of the clinical pharmacology of (-)NPA and levodopa in Parkinson's disease

Journal of Neurology, Neurosurgery & Psychiatry, 1991

Direct acting dopamine agonists are generally less effective than levodopa in relieving symptoms ... more Direct acting dopamine agonists are generally less effective than levodopa in relieving symptoms of Parkinson's disease. In an attempt to quantitate and explain this situation, the acute motor responses to intravenous injections of the dopamine agonist, (-)-N-n-propylnorapomorphine hydrochloride (NPA), were compared with those of the dopamine precursor, levodopa. At optimum dose levels, the acute anti-Parkinsonian efficacy of NPA averaged only about 50% of maximum, while essentially total symptom suppression was obtained with levodopa in patients previously treated with the amine precursor. Dyskinesia severity, however, was similar with the two drugs. These differences in anti-Parkinsonian efficacy may reflect the fact that while NPA acts mainly on D-2 dopamine receptors, levodopa results in stimulation of both the D-1 and D-2 subsets of receptors at a more physiological ratio. Future efforts to develop dopamine agonists for the treatment of Parkinsonian symptoms may thus have to consider focusing on drugs having pharmacological profile more similar to that of dopamine.

Research paper thumbnail of No evidence for altered muscle mitochondrial function in Parkinson's disease

Journal of Neurology, Neurosurgery & Psychiatry, 1993

Recent reports indicate that reductions in mitochondrial respiratory chain function occur in subs... more Recent reports indicate that reductions in mitochondrial respiratory chain function occur in substantia nigra, platelets, and muscle from patients with Parkinson's disease. To confirm and further characterise the presence of a generally distributed mitochondrial defect, mitochondrial metabolism was evaluated in muscle obtained from subjects with Parkinson's disease and from normal controls. Oxygen consumption rates in muscle mitochondria represented by complex I, complexes II-III, or complex IV did not differ between the two groups. Likewise, activities of rotenone sensitive NADH cytochrome c reductase, succinate cytochrome c reductase, or cytochrome oxidase in muscle mitochondria were not significantly different between Parkinsonian and control subjects. These findings fail to provide support for a generalised defect in mitochondrial function in Parkinson's disease but do not exclude an abnormality in respiratory function confined to the substantia nigra.

Research paper thumbnail of Contact sex pheromone in the tsetse flyGlossina pallidipes (Austen) Identification and Synthesis

Journal of Chemical Ecology, 1984

Adult male G. pallidipes attempted to copulate with decoys treated with a branched paraffin obtai... more Adult male G. pallidipes attempted to copulate with decoys treated with a branched paraffin obtained from laboratory-reared female flies. The compound causing maximal response was isolated and identified as 13,23-dimethylpentatriacontane. The synthesized compound elicited increasing responses with increasing doses. This sex-and species-specific compound was always present in physiological amounts in females, as it increased from 2 #g at emergence to 10 #g per female at 14 days. It was present in wild-caught females from a wide geographical range.

Research paper thumbnail of ERK inhibitor PD98059 enhances docetaxel-induced apoptosis of androgen-independent human prostate cancer cells

International Journal of Cancer, 2003

Anticancer drugs docetaxel and vinorelbine suppress cell growth by altering microtubule assembly ... more Anticancer drugs docetaxel and vinorelbine suppress cell growth by altering microtubule assembly and activating the proapoptotic signal pathway. Vinorelbine and docetaxel have been approved for treating several advanced cancers. However, their efficacy in the management of advanced hormone-refractory prostate cancer remains to be clarified. Microtubule damage by some anticancer drugs can activate the ERK survival pathway, which conversely compromises chemotherapeutic efficacy. We analyzed the effect of ERK inhibitors PD98059 and U0126 on vinorelbine- and docetaxel-induced cell growth suppression of androgen-independent prostate cancer cells. In androgen-independent C-81 LNCaP cells, inhibition of ERK by PD98059, but not U0126, plus docetaxel resulted in enhanced growth suppression by an additional 20% compared to the sum of each agent alone (p < 0.02). The combination treatment of docetaxel plus PD98059 also increased cellular apoptosis, which was in part due to the inactivation of Bcl-2 by increasing phosphorylated Bcl-2 by more than 6-fold and Bax expression by 3-fold over each agent alone. At these dosages, docetaxel alone caused only marginal phosphorylation of Bcl-2 (10%). Docetaxel plus U0126 had only 20% added effect on Bcl-2 phosphorylation compared to docetaxel alone. Nevertheless, both U0126 and PD98059 exhibited an enhanced effect on docetaxel-induced growth suppression in PC-3 cells. No enhanced effect was observed for vinorelbine plus PD98059 or U0126. Thus, the combination therapy of docetaxel plus PD98059 may represent a new anticancer strategy, requiring lower drug dosages compared to docetaxel monotherapy. This may lower the cytotoxicity and enhance tumor suppression in vivo. This finding of a combination effect could be of potential clinical importance in treating hormone-refractory prostate cancer.

Research paper thumbnail of Renal Impairment of Pure Autonomic Failure

Hypertension, 2009

Supine hypertension is difficult to manage in patients with pure autonomic failure (PAF), because... more Supine hypertension is difficult to manage in patients with pure autonomic failure (PAF), because treatment can worsen orthostatic hypotension. Supine hypertension in PAF has been associated with left ventricular hypertrophy, but end organ damage in the kidney has not been assessed. We reviewed hemodynamic and laboratory data of 64 male patients with PAF who were 69Ϯ11 (meanϮSD) years old. Systolic blood pressure fell by 67Ϯ40 mm Hg within 10 minutes of standing, with an inappropriately low 13Ϯ11-bpm increase in heart rate. Plasma norepinephrine levels were below normal (0.62Ϯ0.32 nmol/L supine and 1.28Ϯ1.25 nmol/L standing). A control data set of 75 men (67Ϯ12 years) was obtained from a deidentified version of the Vanderbilt University Medical Center electronic medical chart database. Compared with controls, PAF patients had lower hemoglobin (8.3Ϯ0.9 versus 9.3Ϯ0.8 mmol/L; PϽ0.001), packed cell volume (0.40Ϯ0.04 versus 0.45Ϯ0.04; PϽ0.001), and red blood cell count (4.4Ϯ0.5ϫ10 12 versus 5.0Ϯ0.5ϫ10 12 cells/L; PϽ0.001). Serum creatinine and blood urea nitrogen levels were elevated in patients. Forty-eight percent of patients with PAF had supine hypertension (supine systolic blood pressure: Ն150 mm Hg). Serum creatinine was higher in patients with supine hypertension (133Ϯ44 versus 106Ϯ27 mol/L; Pϭ0.021) and estimated glomerular filtration rate was lower (57Ϯ22 versus 70Ϯ20 mL/min per 1.73 m 2 ; Pϭ0.022) compared with patients who did not have supine hypertension. These findings may indicate that renal function is diminished in PAF in association with supine hypertension. (Hypertension. 2009;54:1057-1061.) Key Words: pure autonomic failure Ⅲ orthostatic hypotension Ⅲ supine hypertension Ⅲ renal insufficiency Ⅲ anemia

Research paper thumbnail of Perceived Benefit of CACREP (2001) Core Curriculum Standards

Counselor Education and Supervision, Jun 1, 2004

... Jason M. McGlothlin, Counseling and Human Development Services, Kent State University;Thomas ... more ... Jason M. McGlothlin, Counseling and Human Development Services, Kent State University;Thomas E. Davis, Department of Counseling and Higher ... Loesch and Vacc (1994) found that counselors who took the NCE typically scored lowest on the questions pertaining to career ...

Research paper thumbnail of Perceived Expectations Related to Promotion and Tenure: A National Survey of CACREP Program Liaisons

Counselor Education and Supervision, Dec 1, 2006

The purpose of the present study was to determine the perceptions of expectations and practices t... more The purpose of the present study was to determine the perceptions of expectations and practices that contribute to decisions regarding promotion and tenure for counselor educators. Council for Accreditation of Counseling and Related Educational Programs liaisons for 74 counselor education programs responded to an Internet-based survey about perceptions of promotion and tenure practices in their programs and institutions. The responses indicate that relatively equal emphasis is placed on teaching, scholarship, and service. Implications for defining promotion and tenure criteria are discussed, and recommendations for further research are provided.

Research paper thumbnail of Dosage compensation proteins targeted to X chromosomes by a determinant of hermaphrodite fate

Science, 1999

rodite-specific sation) genes S~C (lo, (sex 11). and In dosage hermaphrodites, compen-Targeted to... more rodite-specific sation) genes S~C (lo, (sex 11). and In dosage hermaphrodites, compen-Targeted to X Chromosomes by these genes activate dosage compensation and the genetic pathway for hermaphrodite sexual development (12-15). Both SDC-2 a Determinant of and S D C~ are necessary for localization of

Research paper thumbnail of Deep brain stimulation may reduce the relative risk of clinically important worsening in early stage Parkinson's disease

Parkinsonism & related disorders, Jan 11, 2015

The Vanderbilt pilot trial of deep brain stimulation (DBS) in early Parkinson's disease (PD) ... more The Vanderbilt pilot trial of deep brain stimulation (DBS) in early Parkinson's disease (PD) enrolled patients on medications six months to four years without motor fluctuations or dyskinesias. We conducted a patient-centered analysis based on clinically important worsening of motor symptoms and complications of medical therapy for all subjects and a subset of subjects with a more focused medication duration. Continuous outcomes were also analyzed for this focused cohort. A post hoc analysis was conducted on all subjects from the pilot and a subset of subjects taking PD medications 1-4 years at enrollment. Clinically important worsening is defined as both a ≥ 3 point increase in UPDRS Part III and a ≥ 1 point increase in Part IV. DBS plus optimal drug therapy (DBS + ODT) subjects experienced a 50-80% reduction in the relative risk of worsening after two years. The DBS + ODT group was improved compared to optimal drug therapy (ODT) at each time point on Total UPDRS and Part III (...

Research paper thumbnail of Ventricular Width and Complicated Recovery following Deep Brain Stimulation Surgery

Stereotactic and Functional Neurosurgery, 2012

Candidates for deep brain stimulation (DBS) must be carefully evaluated to balance expected benef... more Candidates for deep brain stimulation (DBS) must be carefully evaluated to balance expected benefits with the possibility of serious complications. Several predictive factors exist but are imperfect. The aim of this study was to determine whether linear measurements of the lateral ventricles predict complications following DBS. We retrospectively studied a cohort of DBS patients. The primary outcome was postoperative confusion; secondary outcomes were discharge disposition and all in-hospital complications. For each case, a control matched for age, sex, diagnosis, and DBS target was identified. Linear measurements were made from routine preoperative axial MRIs for both cases and controls. A total of 40 patients met one or more of the end points. Patients with postoperative confusion had a significantly larger minimum width of the lateral ventricles than controls. Patients discharged to a higher level of care and those with any complications also had significantly greater maximum and minimum ventricular widths than controls. These results suggest that preoperative measurement of the maximum and minimum width of the lateral ventricles may help predict which patients are at risk for complicated recoveries following DBS.

Research paper thumbnail of Atypical junctional melanocytic proliferations in benign lichenoid keratosis

Human pathology, 2003

Melanocytic lesions with lichenoid regression may mimic a benign lichenoid keratosis (BLK) histol... more Melanocytic lesions with lichenoid regression may mimic a benign lichenoid keratosis (BLK) histologically. A total of 336 BLKs were reviewed and deeper sections obtained to determine the frequency of this phenomenon. Two cases (0.6%) showed at least 1 melanocytic nest or junctional multinucleated melanocyte (starburst melanocyte) on deeper sections confirmed by MART-1 immunostaining. Both of these cases demonstrated solar elastosis, and 1 case had an effaced rete ridge pattern. Not included in the histological study are 5 additional cases in which the initial slide showed only lichenoid dermatitis, but deeper sections obtained before to the initial sign-out revealed a melanocytic proliferation. These 5 cases would have been signed out as "consistent with BLK" if deeper sections had not been obtained. Fluorescent in situ hybridization (FISH) was performed on 3 cases; in each case, the melanocytes demonstrated a loss of chromosome 9p21 DNA copy number. The finding of nests o...

Research paper thumbnail of Neuropsychological effects of deep brain stimulation for Parkinson′s disease

Surgical Neurology International, 2013

Putative changes of cognition after deep brain stimulation (DBS) in patients with Parkinson&a... more Putative changes of cognition after deep brain stimulation (DBS) in patients with Parkinson's disease (PD) are a matter of debate. The aim of this study was to assess cognitive abilities before and following bilateral subthalamic nucleus (STN) DBS and to review the available literature. Twenty patients underwent bilateral DBS of the STN. Cognitive skills were assessed in a standardized fashion before and at least at 12 months after the surgical intervention. There was a significant decline of both semantic and phonematic verbal fluency and a mild trend for a deterioration of verbal memory after DBS. Mood, general cognitive screening, and visospatial abilities remained unchanged. STN DBS in the treatment of PD has resulted in a significant reduction of motor symptoms and improved independence and quality of life in appropriately selected patients. However, it may have isolatable effects on verbal fluency and related function. Case series in the literature reported similar findings. Potential candidates for DBS should be counseled about the risk of mild cognitive declines.

Research paper thumbnail of Deep brain stimulation in early Parkinson’s disease: Enrollment experience from a pilot trial

Parkinsonism & Related Disorders, 2012

Background-Deep brain stimulation (DBS) of the subthalamic nucleus is an accepted therapy for adv... more Background-Deep brain stimulation (DBS) of the subthalamic nucleus is an accepted therapy for advanced Parkinson's disease (PD). In animal models, pharmacologic ablation and stimulation of the subthalamic nucleus have resulted in clinical improvement and, in some cases, improved survival of dopaminergic neurons. DBS has not been studied in the early stages of PD, but early application should be explored to evaluate safety, efficacy, and the potential to alter disease progression.

Research paper thumbnail of Multiple system atrophy: new developments in pathophysiology and therapy

Parkinsonism & Related Disorders, 2001

There have been substantial advances in the last five years in understanding the basic and clinic... more There have been substantial advances in the last five years in understanding the basic and clinical pathophysiology underlying multiple system atrophy (MSA). Identification of glial cytoplasmic inclusions has been the most important organizing principle for further elucidation of underlying mechanisms. Recently, several unexpected developments at the clinical level have been reported. In this article, we will focus on two of

Research paper thumbnail of Familial essential tremor with apparent autosomal dominant inheritance: Should we also consider other inheritance modes?

Movement Disorders, 2006

A positive family history is present in many patients with essential tremor (ET), but twin studie... more A positive family history is present in many patients with essential tremor (ET), but twin studies and segregation analysis have suggested that ET is not entirely a genetic disorder. Two genetic loci have been identified in autosomal dominant (AD) ET and polymorphisms in the DRD3 and HS1-BP3 genes have been proposed as the possible susceptibility factors for ET. There is also evidence for further genetic heterogeneity. We evaluated 4 unrelated large kindreds with ET with an apparent AD mode of transmission. Each kindred spanned at least 3 generations and contained at least 13 living affected subjects who met criteria for definitive ET. None of the pedigrees had evidence for inheritance of ET from both parents. Known genetic ET loci were excluded in these families. We detected a preferential transmission of ET in every kindred and the proportion of affected offspring varied from 75% to 90% (P Ͻ 0.05) in the generations with complete ascertainment. Our data indicate that non-Mendelian preferential transmission of an affected allele is a feature in many ET kindreds with multiple affected members and an apparent AD mode of inheritance. ET may have a complex etiology. Additional genetic models need to be considered, including an interaction of susceptibility genes and environmental risk factors.

Research paper thumbnail of Treatment of parkinson's disease with the partial dopamine agonist EMD 49980

Movement Disorders, 1993

The motor effects of the partial dopamine agonist EMD 49980 were evaluated in parkinsonian patien... more The motor effects of the partial dopamine agonist EMD 49980 were evaluated in parkinsonian patients under controlled conditions. EMD 49980 monotherapy resulted in a mild improvement in parkinsonian symptoms, but when co-administered with levodopa, had no significant effect on dyskinesias or on the antiparkinsonian effect of the dopamine precursor. These results suggest that EMD 49980 exerts a net weak dopamine agonist effect but fails to ameliorate levodopa-induced dyskinesias.

Research paper thumbnail of Effect of aging and dopaminomimetic therapy on mitochondrial respiratory function in Parkinson's disease

Movement Disorders, 1992

Oxygen consumption and enzyme activity were evaluated in platelet mitochondria from 17 patients w... more Oxygen consumption and enzyme activity were evaluated in platelet mitochondria from 17 patients with Parkinson's disease. In comparison with age-matched controls, no consistent abnormality could be discerned in complex I, complex 11-111, or complex IV oxygen consumption, or in the enzyme activity of these respiratory chain complexes. Neither chronic therapy with levodopdcarbidopa alone nor in combination with deprenyl significantly affected any measure of mitochondrial respiratory function. There was no discernible relationship between patient age or disease severity and any parameter of mitochondrial respiration. Moreover, blood lactate levels following glucose loading were not different in patients and controls. These results fail to support the occurrence of a generalized defect in any mitochondrial respiratory function in Parkinson's disease.

Research paper thumbnail of Milacemide therapy for Parkinson's disease

Movement Disorders, 1993

The clinical effects of central glutamatergic stimulation by the glycine prodrug milacemide were ... more The clinical effects of central glutamatergic stimulation by the glycine prodrug milacemide were studied in six patients with Parkinson's disease under double-blind, placebo-controlled conditions. When administered as monotherapy at a single oral dose of 1,200 mg, the drug increased overall parkinsonian severity transiently, mostly due to an effect on rigidity. Milacemide did not, however, alter levodopa-induced dyskinesias. These results support the view that drugs acting on the glutamatergic system can influence motor function in patients with extrapyramidal movement disorders and that pharmaceutical agents that selectively block certain subtypes of glutamate receptors may ameliorate parkinsonian symptoms.

Research paper thumbnail of Botulinum toxin type A therapy during pregnancy

Movement Disorders, 2004

16. Kompoliti K. Estrogen and movement disorders. Clin Neuropharmacol 1999;22:318 -326. 17. Moris... more 16. Kompoliti K. Estrogen and movement disorders. Clin Neuropharmacol 1999;22:318 -326. 17. Morissette M., Paola DT. Effect of chronic estradiol and progesterone treatments of ovariectomized rats on brain dopamine uptake sites. J Neurochem 1993;60:1876 -1881. 18. Strijks E., Kremer MAJ, Horstink M. Effects of female sex steroids on Parkinson's disease in postmenopausal women. Clin Neuropharmacol 1999;22:93-97. 19. Cabrera RJ, Navarro CE. Progesterone in vitro increases NMDAevoked [3H] dopamine release from striatal slices in proestrus rats. Neuropharmacology 1996;35:175-178. 20. Nuwayhid SJ, Werling LL. Steroids modulate N-methyl-D-aspartate-stimulated [3H] dopamine release from rat striatum via sigma receptors. J Pharmacol Exp Ther 2003;306:934 -940. 21. Cabrera RJ, Bregonzio C, Lanconi M, Mampel A. Allopregnanolone increase in striatal N-methyl-D-aspartic acid evoked [3H] dopamine release is estrogen and progesterone dependent. Cell

Research paper thumbnail of Deep brain stimulation in early stage Parkinson's disease: operative experience from a prospective randomised clinical trial

Journal of Neurology, Neurosurgery & Psychiatry, 2012

Recent evidence suggests that deep brain stimulation of the subthalamic nucleus (STN-DBS) may hav... more Recent evidence suggests that deep brain stimulation of the subthalamic nucleus (STN-DBS) may have a disease modifying effect in early Parkinson's disease (PD). A randomised, prospective study is underway to determine whether STN-DBS in early PD is safe and tolerable. 15 of 30 early PD patients were randomised to receive STN-DBS implants in an institutional review board approved protocol. Operative technique, location of DBS leads and perioperative adverse events are reported. Active contact used for stimulation in these patients was compared with 47 advanced PD patients undergoing an identical procedure by the same surgeon. 14 of the 15 patients did not sustain any long term (>3 months) complications from the surgery. One subject suffered a stroke resulting in mild cognitive changes and slight right arm and face weakness. The average optimal contact used in symptomatic treatment of early PD patients was: anterior -1.1±1.7 mm, lateral 10.7±1.7 mm and superior -3.3±2.5 mm (anterior and posterior commissure coordinates). This location is statistically no different (0.77 mm, p>0.05) than the optimal contact used in the treatment of 47 advanced PD patients. The perioperative adverse events in this trial of subjects with early stage PD are comparable with those reported for STN-DBS in advanced PD. The active contact position used in early PD is not significantly different from that used in late stage disease. This is the first report of the operative experience from a randomised, surgical versus best medical therapy trial for the early treatment of PD.

Research paper thumbnail of Comparison of the clinical pharmacology of (-)NPA and levodopa in Parkinson's disease

Journal of Neurology, Neurosurgery & Psychiatry, 1991

Direct acting dopamine agonists are generally less effective than levodopa in relieving symptoms ... more Direct acting dopamine agonists are generally less effective than levodopa in relieving symptoms of Parkinson's disease. In an attempt to quantitate and explain this situation, the acute motor responses to intravenous injections of the dopamine agonist, (-)-N-n-propylnorapomorphine hydrochloride (NPA), were compared with those of the dopamine precursor, levodopa. At optimum dose levels, the acute anti-Parkinsonian efficacy of NPA averaged only about 50% of maximum, while essentially total symptom suppression was obtained with levodopa in patients previously treated with the amine precursor. Dyskinesia severity, however, was similar with the two drugs. These differences in anti-Parkinsonian efficacy may reflect the fact that while NPA acts mainly on D-2 dopamine receptors, levodopa results in stimulation of both the D-1 and D-2 subsets of receptors at a more physiological ratio. Future efforts to develop dopamine agonists for the treatment of Parkinsonian symptoms may thus have to consider focusing on drugs having pharmacological profile more similar to that of dopamine.

Research paper thumbnail of No evidence for altered muscle mitochondrial function in Parkinson's disease

Journal of Neurology, Neurosurgery & Psychiatry, 1993

Recent reports indicate that reductions in mitochondrial respiratory chain function occur in subs... more Recent reports indicate that reductions in mitochondrial respiratory chain function occur in substantia nigra, platelets, and muscle from patients with Parkinson's disease. To confirm and further characterise the presence of a generally distributed mitochondrial defect, mitochondrial metabolism was evaluated in muscle obtained from subjects with Parkinson's disease and from normal controls. Oxygen consumption rates in muscle mitochondria represented by complex I, complexes II-III, or complex IV did not differ between the two groups. Likewise, activities of rotenone sensitive NADH cytochrome c reductase, succinate cytochrome c reductase, or cytochrome oxidase in muscle mitochondria were not significantly different between Parkinsonian and control subjects. These findings fail to provide support for a generalised defect in mitochondrial function in Parkinson's disease but do not exclude an abnormality in respiratory function confined to the substantia nigra.

Research paper thumbnail of Contact sex pheromone in the tsetse flyGlossina pallidipes (Austen) Identification and Synthesis

Journal of Chemical Ecology, 1984

Adult male G. pallidipes attempted to copulate with decoys treated with a branched paraffin obtai... more Adult male G. pallidipes attempted to copulate with decoys treated with a branched paraffin obtained from laboratory-reared female flies. The compound causing maximal response was isolated and identified as 13,23-dimethylpentatriacontane. The synthesized compound elicited increasing responses with increasing doses. This sex-and species-specific compound was always present in physiological amounts in females, as it increased from 2 #g at emergence to 10 #g per female at 14 days. It was present in wild-caught females from a wide geographical range.

Research paper thumbnail of ERK inhibitor PD98059 enhances docetaxel-induced apoptosis of androgen-independent human prostate cancer cells

International Journal of Cancer, 2003

Anticancer drugs docetaxel and vinorelbine suppress cell growth by altering microtubule assembly ... more Anticancer drugs docetaxel and vinorelbine suppress cell growth by altering microtubule assembly and activating the proapoptotic signal pathway. Vinorelbine and docetaxel have been approved for treating several advanced cancers. However, their efficacy in the management of advanced hormone-refractory prostate cancer remains to be clarified. Microtubule damage by some anticancer drugs can activate the ERK survival pathway, which conversely compromises chemotherapeutic efficacy. We analyzed the effect of ERK inhibitors PD98059 and U0126 on vinorelbine- and docetaxel-induced cell growth suppression of androgen-independent prostate cancer cells. In androgen-independent C-81 LNCaP cells, inhibition of ERK by PD98059, but not U0126, plus docetaxel resulted in enhanced growth suppression by an additional 20% compared to the sum of each agent alone (p < 0.02). The combination treatment of docetaxel plus PD98059 also increased cellular apoptosis, which was in part due to the inactivation of Bcl-2 by increasing phosphorylated Bcl-2 by more than 6-fold and Bax expression by 3-fold over each agent alone. At these dosages, docetaxel alone caused only marginal phosphorylation of Bcl-2 (10%). Docetaxel plus U0126 had only 20% added effect on Bcl-2 phosphorylation compared to docetaxel alone. Nevertheless, both U0126 and PD98059 exhibited an enhanced effect on docetaxel-induced growth suppression in PC-3 cells. No enhanced effect was observed for vinorelbine plus PD98059 or U0126. Thus, the combination therapy of docetaxel plus PD98059 may represent a new anticancer strategy, requiring lower drug dosages compared to docetaxel monotherapy. This may lower the cytotoxicity and enhance tumor suppression in vivo. This finding of a combination effect could be of potential clinical importance in treating hormone-refractory prostate cancer.

Research paper thumbnail of Renal Impairment of Pure Autonomic Failure

Hypertension, 2009

Supine hypertension is difficult to manage in patients with pure autonomic failure (PAF), because... more Supine hypertension is difficult to manage in patients with pure autonomic failure (PAF), because treatment can worsen orthostatic hypotension. Supine hypertension in PAF has been associated with left ventricular hypertrophy, but end organ damage in the kidney has not been assessed. We reviewed hemodynamic and laboratory data of 64 male patients with PAF who were 69Ϯ11 (meanϮSD) years old. Systolic blood pressure fell by 67Ϯ40 mm Hg within 10 minutes of standing, with an inappropriately low 13Ϯ11-bpm increase in heart rate. Plasma norepinephrine levels were below normal (0.62Ϯ0.32 nmol/L supine and 1.28Ϯ1.25 nmol/L standing). A control data set of 75 men (67Ϯ12 years) was obtained from a deidentified version of the Vanderbilt University Medical Center electronic medical chart database. Compared with controls, PAF patients had lower hemoglobin (8.3Ϯ0.9 versus 9.3Ϯ0.8 mmol/L; PϽ0.001), packed cell volume (0.40Ϯ0.04 versus 0.45Ϯ0.04; PϽ0.001), and red blood cell count (4.4Ϯ0.5ϫ10 12 versus 5.0Ϯ0.5ϫ10 12 cells/L; PϽ0.001). Serum creatinine and blood urea nitrogen levels were elevated in patients. Forty-eight percent of patients with PAF had supine hypertension (supine systolic blood pressure: Ն150 mm Hg). Serum creatinine was higher in patients with supine hypertension (133Ϯ44 versus 106Ϯ27 mol/L; Pϭ0.021) and estimated glomerular filtration rate was lower (57Ϯ22 versus 70Ϯ20 mL/min per 1.73 m 2 ; Pϭ0.022) compared with patients who did not have supine hypertension. These findings may indicate that renal function is diminished in PAF in association with supine hypertension. (Hypertension. 2009;54:1057-1061.) Key Words: pure autonomic failure Ⅲ orthostatic hypotension Ⅲ supine hypertension Ⅲ renal insufficiency Ⅲ anemia