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Biomedical subjects

Donald G Grosset

Publications and source records attributed to Donald G Grosset.

14 recordsLinked to original sources
PubMed2006

Pergolide versus levodopa monotherapy in early Parkinson's disease patients: The PELMOPET study.

Dopamine agonists are used as initial treatment in patients with Parkinson's disease (PD) to reduce incidence and severity of motor complications. This paradigm is based on long-term studies, allowing "rescue" therapy with levodopa. The present strict monotherapy study (PELMOPET, the acronym for the pergolide-versus-L-dopa-monotherapy-and-positron-emission-tomography trial) evaluated the efficacy and safety of pergolide versus levodopa without levodopa "rescue" medication. This multicenter, double-blind, randomized, 3-year trial compared pergolide monotherapy (n=148) with levodopa monotherapy (n=146) in dopamine-naive patients with early PD (Hoehn and Yahr stage 1-2.5). Primary efficacy measures were clinical efficacy, severity and time to onset of motor complications, and disease progression. During the 3 years, severity of motor complications was significantly lower and time to onset of dyskinesia was significantly delayed in the group receiving pergolide (3.23 mg/day) compared with those receiving levodopa (504 mg/day). However, time to onset of motor complications was not longer in patients receiving pergolide after 3 years. Symptomatic relief (assessed by Unified Parkinson's Disease Rating Scale [UPDRS], UPDRS II, and III, Clinical Global Impressions [CGI] severity, and CGI and Patient Global Impressions [PGI] improvement) was significantly greater in patients receiving levodopa. Adverse events led to discontinuation of therapy in 17.6% of pergolide patients and 9.6% of levodopa patients. This is the first study comparing strict monotherapy with a dopamine agonist versus levodopa in previously untreated early PD. In principle, both levodopa and a dopamine agonist such as pergolide seem to be suitable options as initial PD therapy. The choice remains with the treating physician based on the different efficacy and adverse event profiles.

Adult↗
PubMed2006

Successful antiparkinsonian medication withdrawal in patients with Parkinsonism and normal FP-CIT SPECT.

Between 4% and 14% of patients diagnosed with Parkinson's disease and entering clinical trials have normal presynaptic dopaminergic imaging. The effects of antiparkinsonian therapy have varied in these studies, and the consequences of stopping treatment are not reported. We present 11 patients who initially fulfilled diagnostic criteria and were treated for Parkinson's disease but in whom emerging diagnostic doubts led to antiparkinsonian therapy withdrawal, which was achieved without deterioration. Such cases represent a nondegenerative form of Parkinsonism, which does not benefit from dopaminergic therapy. Prospective vigilance regarding this category is of importance in clinical practice and clinical trials.

Aged↗
PubMed2006

Two-year follow-up in 150 consecutive cases with normal dopamine transporter imaging.

BACKGROUND AND AIMS: Functional pre-synaptic dopamine brain imaging is generally abnormal when parkinsonism is degenerative (such as in idiopathic Parkinson's disease) and normal in patients with non-degenerative movement disorder (such as essential tremor). However, some patients diagnosed as early Parkinson's disease have normal presynaptic dopamine imaging. Follow-up of patients with normal imaging should help determine whether such patients truly have degenerative parkinsonism (and therefore represent false negative imaging results), or emerge as cases of non-degenerative parkinsonism (and therefore represent initial clinical over-diagnosis of Parkinson's disease). METHODS AND RESULTS: One hundred and fifty cases with normal I-FP-CIT SPECT undertaken during routine care over a 3-year period were reviewed 2.4 years (interquartile range, 2.2-3.1 years) after SPECT. Diagnosis after follow-up was non-degenerative parkinsonism or tremor in 146 (97%), who did not progress clinically, and degenerative parkinsonism in four (3%), in whom clinical progression was noted. Anti-Parkinson therapy was used in 36, and withdrawn in 27 with no deterioration in 25. Patients strictly fulfilling Brain Bank criteria (part 1) were more likely to undergo a trial of anti-Parkinson therapy (P < 0.05) but were no more likely to maintain or respond to anti-Parkinson therapy than those not fulfilling criteria. CONCLUSION: The clinical profile and therapy response during follow-up of patients with normal presynaptic dopamine imaging supports the diagnosis of a non-degenerative movement disorder in nearly all cases.

Antiparkinson Agents↗
PubMed2005

Patient-perceived involvement and satisfaction in Parkinson's disease: effect on therapy decisions and quality of life.

Patient-centered consultation styles are associated with higher patient satisfaction and improved health outcomes in diabetes and hypertension. In outpatient neurology, dissatisfaction with communication relates significantly to noncompliance. We undertook a single-center study in Parkinson's disease (PD) using standardized questionnaires to score patient-perceived involvement in therapy decisions (score 4 = low to 25 = high) and satisfaction with the consultation (score 1 = low to 7 = high). Correlation was tested against health outcomes of Unified Parkinson's Disease Rating Scale (UPDRS) Motor score, activities of daily living (UPDRS 2 and Schwab and England), Parkinson's disease quality of life (PDQ-39), Mini-Mental State Examination (MMSE), and Geriatric Depression Scale (GDS). Of 117 patients enrolled, 107 (91%) fully completed the questionnaires. Mean patient-perceived involvement scored 14.4 (SD, 2.8). Mean satisfaction scored 5.3 (SD 0.7). Higher involvement was associated with increased satisfaction (r = 0.28; P = 0.003), particularly distress relief (r = 0.38; P < 0.0001). Communication scores correlated significantly with compliance intent (r = 0.6; P < 0.0001). There was no correlation between either involvement or satisfaction and UPDRS, Schwab and England, MMSE, or GDS. Quality of life was significantly associated with depression, UPDRS, duration of PD, compliance intent, and satisfaction. The significant positive association between compliance intent and quality of life in the more satisfied patient replicates findings in other disease areas. Due attention to these aspects in delivering care to the PD patient is appropriate.

Activities of Daily Living↗
PubMed2005

Medicine-taking behavior: implications of suboptimal compliance in Parkinson's disease.

Management of Parkinson's disease (PD) depends primarily on oral medication. There are several drug classes and multiple doses and formulations, which make optimizing therapy complex. Variable drug absorption and the short half-life of most antiparkinson treatments, especially levodopa, are a main focus in understanding complications and have encouraged alternative delivery systems to limit fluctuation and dyskinesia at later stages. Comparatively little attention is paid to the way patients take their oral medication. Variable medicine-taking behavior can affect the clinician's understanding of the diagnosis and rate of progression, and further prescription of PD medication. Medicine overuse in later stage PD is well documented and causes psychiatric disturbance and increases motor complications, but evidence of undertreatment and erratic intake is emerging, which is likely to affect motor control and quality of life adversely. Methods of quantifying compliance are compared for accuracy and limitations. Understanding medicine-taking behavior is a first step in optimizing therapy and requires consideration of a patient's personal beliefs about their medicines. Although the benefits of regularizing oral medicine-taking in a practical, achievable way in PD remain untested, such an approach might prolong and smooth the benefits of oral medication and is worthy of further research.

Antiparkinson Agents↗
PubMed2005

Suboptimal medication adherence in Parkinson's disease.

Patients take less medication than prescribed in many disease areas but evidence for suboptimal therapy adherence in Parkinson's disease (PD) is limited. A single-center observational study of antiparkinsonian medication was undertaken using electronic monitoring (MEMS; Aardex, Zug, Switzerland) over 3 months. Of 68 patients approached, 6 declined and 8 dropped out, leaving 54 patients (taking 117 preparations) with available data. Poorer compliance was associated significantly with younger age, with taking more antiparkinsonian tablets per day, with higher depression scores, and with poorer quality of life. Of the 54 evaluable patients, 11 (20%) had average total compliance of under 80% (underusers) and 43 (80%) had average total compliance of over 80% (satisfactory adherence). Underusers had median total compliance of 65% (interquartile range, 37-74) versus 98% (interquartile range, 93-102) in the satisfactory adherence group. Timing compliance (number of doses taken in the correct time interval) was poor in both underusers (median, 11%; interquartile range, 2-20) and those with satisfactory adherence (median, 25%; interquartile range, 11-73). In conclusion, poorer compliance is associated with younger age, depression, and more tablets per day, and one-fifth of PD patients underuse medication. Consideration of drug therapy adherence has implications in the management of PD.

Age Factors↗
PubMed2004

GPI-1485 (Guilford).

GPI-1485 is a neuroimmunophilin ligand that binds to FK-506-binding proteins and is under development by Guilford for the potential treatment of erectile dysfunction following nerve injury during prostate resection and Parkinson's disease. In August 2002, phase II clinical trials investigating GPI-1485 for Parkinson's disease commenced, and in November 2003, further phase II trials commenced for post-prostatectomy erectile dysfunction.

Administration, Oral↗
PubMed2003

Prospective study of presynaptic dopaminergic imaging in patients with mild parkinsonism and tremor disorders: part 1. Baseline and 3-month observations.

To record prospectively, from early presentation, the clinical features of parkinsonism and tremor disorders, in relation to evidence of dopaminergic deficit shown with [(123)I]-FP-CIT (DaTSCAN, Amersham Health) single photon emission computerised tomography (SPECT). Clinical signs were recorded in 62 patients, of whom 24 failed standard Parkinson's disease (PD) and essential tremor criteria, and 38 fulfilled UK Brain Bank step 1 PD criteria. Striatal radioligand uptake was graded visually as normal or abnormal, and specific:nonspecific ratios were calculated. Bradykinesia and rigidity showed significant overall association with abnormal scans (P < or = 0.003), but rest tremor did not (P = NS). In the 24 patients not fulfilling specific criteria (mean age 63 [SD 9] years, disease duration 3 [SD 4] years), 10 (42%) had abnormal visual SPECT assessment and 14 (58%) had normal scans. Of 38 patients with early PD by clinical criteria (mean age 60 [SD 9] years, disease duration 3 [SD 1.7] years), 33 (87%) were visually abnormal. Baseline clinical diagnosis corresponded with SPECT imaging results in 51 of 62 cases (82%), which increased to 56 of 62 cases (90%) with amendment of seven clinical diagnoses at 3 months (blind to SPECT results). Akinetic-rigid cardinal diagnostic features of parkinsonism associate well with dopaminergic deficit in patients with early and mild clinical features. When these clinical features are uncertain, or the patient fails clinical diagnostic criteria, testing for dopaminergic deficit with [(123)I]-FP-CIT SPECT may assist the diagnostic process.

Adult↗
PubMed2003

Role of dopamine transporter imaging in the diagnosis of atypical tremor disorders.

Dopamine transporter (DAT) imaging detects presynaptic dopamine neuronal dysfunction and thereby assists differentiation of conditions with and without dopamine deficit. In atypical tremor disorders, DAT imaging can differentiate between Parkinson's disease (PD), where dopamine deficit is demonstrated on DAT imaging, and essential tremor, where no dopamine deficit is found. DAT imaging may be particularly informative in monosymptomatic rest tremors, benign tremulous Parkinson's syndrome, and in the elderly in whom essential tremor may be accompanied by pseudoparkinsonism.

Aged↗
PubMed2002

Turbulence and circulating cerebral emboli detectable at Doppler ultrasonography: a differentiation study in a stenotic middle cerebral artery model.

BACKGROUND AND PURPOSE: Blood flow within the middle cerebral artery can be monitored by transcranial Doppler (TCD) ultrasonography. Arterial stenosis can produce turbulent flow, but controversy remains regarding the degree of stenosis needed to cause TCD-detectable turbulence. Furthermore, cerebral emboli and turbulent flow may coexist in the same patient. The current study was designed to study the relationship between stenotic degree and TCD-detectable turbulent flow and its differentiation from cerebral emboli. METHODS: A stenotic middle cerebral artery model was constructed to allow the study of different degrees of stenosis. TCD was used to detect the turbulent flow and embolic materials in the circulation model, and signal intensities were analyzed. RESULTS: Turbulent flow was generated with a series of short, asymmetric stenoses in this test. Transition of turbulence from laminar flow began to occur at a moderate degree of stenosis (55% reduction of cross-sectional area) but became dampened at the high degrees of stenoses (>/=75%). Turbulence caused a notable increase in average Doppler signal intensity. However, the degree of stenosis was not associated with signal intensity at the region where turbulence existed, but rather was related to the mean flow velocity measured at the narrowed region. Embolic materials such as air bubbles (30 micro m) and platelet-rich clots (100 micro m) had notably higher Doppler signal intensity than that produced by turbulence. CONCLUSION: TCD-detectable turbulence predominantly developed at a moderate arterial stenosis and its acoustic signature with TCD is different from that caused by air bubbles and platelet-rich clots.

Blood Flow Velocity↗