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Biomedical subjects

G Fabbrini

Publications and source records attributed to G Fabbrini.

At least 73 records · Page 4Linked to original sources
PubMed1987

Controlled release levodopa-carbidopa (CR-5) in the management of parkinsonian motor fluctuations.

Parkinsonian patients receiving long-term levodopa-carbidopa (Sinemet) therapy often develop fluctuations in motor performance. Although maintenance of stable levels of plasma levodopa by means of its continuous intravenous infusion diminishes these fluctuations, practical limitations attending this therapeutic approach have prompted continuing attempts to develop oral controlled release levodopa-carbidopa formulations. In a double-blind, crossover clinical trial, one such preparation, CR-5 (Merck, Sharp & Dohme), produced significantly less plasma levodopa variations and substantially improved motor performance over Sinemet in 15 patients with mild to moderate fluctuations, all but one of whom chose to continue on CR-5 therapy after the study. Eight patients with severe motor fluctuations could not adjust to this preparation during the open phase and consequently withdrew from the study. Subjectively, most patients noted the convenience of less frequent dosing, improved sleep, and the amelioration of early morning akinesia and dystonia.

Adult↗
PubMed1987

Levodopa pharmacokinetic mechanisms and motor fluctuations in Parkinson's disease.

The contribution of the peripheral and central pharmacokinetic mechanisms of levodopa to the pathogenesis of the motor fluctuations that complicate its long-term administration was studied in 28 parkinsonian patients. The rate of levodopa clearance from the general circulation, its plasma half-life, and apparent volume of distribution were indistinguishable between patients with the on-off or the wearing-off phenomenon and those with a stable response to levodopa or those who had not been previously treated with levodopa. Peripheral pharmacokinetic factors are thus unlikely to account for the development of these response fluctuations. Conversely, the efficacy half-time of levodopa differed markedly among the four response groups studied and may provide a quantitative index of central mechanisms that favor the development of the wearing-off and on-off phenomena. Although symptom duration was the best predictor of the severity of untreated parkinsonism, levodopa dose correlated best with response half-time. The wearing-off phenomenon may primarily reflect the loss of buffering capacity caused by degeneration of the dopamine neurons, while the development of the on-off phenomenon appears to require additional postsynaptic changes, possibly at the receptor level.

Administration, Oral↗
PubMed1987

Motor fluctuations in Parkinson's disease: pathogenetic and therapeutic studies.

The response to continuous intravenous infusion of levodopa was evaluated in 23 patients with Parkinson's disease complicated by motor fluctuations. Conversion from oral to intravenous levodopa treatment resulted in an immediate and sustained stabilization of plasma levodopa levels in both the wearing-off and on-off groups. Motor variability also diminished within the first 24 hours of infusion, although to a much greater extent in patients with the wearing-off phenomenon. Over the next 5 to 11 days of intravenous treatment, further reductions in motor fluctuations occurred in both groups, at a substantially faster rate in the wearing-off group than in the on-off group. The degree of immediate stabilization of parkinsonian motor response correlated best with disease duration, whereas the rate of subsequent improvement correlated most closely with levodopa dose. The results support the view that the wearing-off phenomenon may reflect the degeneration of dopamine terminals as a consequence of natural disease progression with a resultant inability to buffer variations in levodopa availability; the on-off phenomenon may reflect additional postsynaptic changes, possibly occurring in response to the nonphysiological fluctuations in synaptic dopamine, which gradually remit during continuous levodopa administration.

Administration, Oral↗
PubMed1987

Selective D-1 dopamine receptor agonist treatment of Parkinson's disease.

Preclinical evidence suggests that the D-1 dopamine receptor contributes to the generation of behaviors used as models for human extrapyramidal disorders. To evaluate the potential of D-1 receptor stimulation in neurologic disease, SKF 38393, a selective D-1 dopamine receptor agonist, was administered to seven patients with idiopathic Parkinson's disease in a double-blind, placebo controlled study. SKF 38393 was found to be rapidly absorbed when administered orally, and to occur in micromolar concentrations in spinal fluid. No change in scores of parkinsonian severity were noted when SKF 38393 was administered alone, or when the drug was combined with intravenous levodopa. The results support the view that the pathophysiology of Parkinson's disease may relate exclusively to the D-2 subclass of dopamine receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1987

Exercise and the antiparkinsonian response to levodopa.

The contribution of acute physical exercise to the motor fluctuations occurring in advanced Parkinson's disease was studied in four patients using a standard treadmill protocol. With a constant optimal-dose intravenous levodopa infusion, no changes in plasma drug levels or antiparkinsonian response were observed during or for 60 min following a 35-min exercise period, during which the work load increased from minimal to vigorous. Although an effect of exercise on levodopa absorption from the gastrointestinal tract cannot be excluded, there seems to be no basis on which to implicate acute physical activity, at levels ordinarily experienced by parkinsonian patients, in the pathogenesis of the fluctuations in motor performance.

Adult↗
PubMed1987

Controlled release levodopa treatment of motor fluctuations in Parkinson's disease.

A controlled release preparation of levodopa-carbidopa, CR III, given every 4 hours to 17 Parkinsonian patients for up to 10 months reduced plasma drug variations and improved motor response fluctuations compared with standard levodopa-carbidopa given every 2 hours. The results support the value of pharmaceutical approaches to the stabilisation of circulating levodopa levels in the treatment of Parkinson's disease.

Adult↗
PubMed1987

Cognitive concomitants of dopamine system stimulation in parkinsonian patients.

Verbal, visuospatial and motor functions were studied in eight Parkinsonian patients both during levodopa stimulated and unstimulated state and in eight matched, untreated, healthy controls. Profound changes in patients' motor status were accompanied by relatively selective effects on delayed verbal memory, a function which was also most impaired compared with controls. With dopaminomimetic therapy, tests of delayed verbal memory consistently improved, but did not reach control performance levels. These results could indicate a functional impairment in the mesocortical dopamine system, which can be attenuated, but not entirely corrected, by dopaminomimetic therapy.

Adult↗
PubMed1987

3-O-methyldopa and motor fluctuations in Parkinson's disease.

High plasma levels of 3-O-methyldopa (OMD) were found in parkinsonian patients chronically treated with levodopa, particularly in those with on-off phenomenon. However, no relation could be established between circulating levels of the levodopa metabolite and the presence of motor response fluctuations at any stage of disease. It appears unlikely that plasma OMD accumulation contributes to the pathogenesis of wearing-off or on-off responses.

Administration, Oral↗
PubMed1987

Levodopa methyl ester treatment of Parkinson's disease.

Intravenously administered levodopa is effective although relatively impractical for the chronic treatment of patients with Parkinson's disease who are disabled by motor fluctuation. In view of its greater solubility, levodopa methyl ester (LDME) was evaluated in seven advanced parkinsonian patients as a potentially more convenient alternative. Compared with oral levodopa, LDME infusions resulted in marked reductions of both plasma levodopa variations and motor response fluctuations in patients with either wearing-off or on-off phenomena. During infusions lasting approximately 1 week, there were no complications except for peripheral vein phlebitis. The results suggest that LDME might be a practical parenteral treatment for those with severe Parkinson's disease. It appears that central venous access or its equivalent will be necessary for its chronic administration.

Administration, Oral↗
PubMed1985

NMR imaging in transient cerebral ischemia.

NMR has proved useful in the detection of Acute Cerebrovascular Disorders (ACVD), providing information related either to the tissue signal intensity and relaxation times, or to the morphological aspects of cerebral structures. Eighteen patients suffering from ischemic Acute Cerebrovascular Disorders were studied. A comparison between NMR imaging and CT scan was performed. Ischemic lesions, presence of edema, presence of reactive gliosis and anatomical vascular anomalies were found.

Acute Disease↗
PubMedDate not supplied

Spinal fluid CRF reduction in Alzheimer's disease.

Abnormalities in several neurotransmitters, including neuropeptides, have been found in postmortem studies of Alzheimer's disease (AD). Recently, corticotropin-releasing factor (CRF) was found to be diminished in cerebral cortex. In this study spinal fluid CRF-immunoreactivity (CRF-I) was determined in 16 patients with mild to moderate AD and 9 age-matched controls. Mean CRF-I levels were significantly lower in Alzheimer patients compared with controls. Furthermore, a tendency for a CRF-I increment with successive spinal fluid aliquots in control subjects was absent in Alzheimer patients. CRF-I levels failed to correlate with measures of disease severity or various tests of cognitive function. These results suggest that involvement of CRF containing neurons may play a secondary rather than a primary role in the pathophysiology of AD.

Aged↗
PubMedDate not supplied

Impact of the International Headache Society criteria on the use of neuroimaging for headache diagnosis in a headache clinic.

OBJECTIVE: To evaluate the impact of the introduction of the International Headache Society (IHS) criteria on the use of neuroimaging for headache diagnosis in a specialist outpatient center. BACKGROUND: The general indications for neuroimaging in headache are a matter of debate. International Headache Society criteria should improve diagnostic accuracy, consequently reducing the use of expensive diagnostic procedures such as brain CT or MRI scan. METHODS: We reviewed the medical records of all 2739 new patients seen in our center from 1984 to 1996, analyzing the records of those patients who underwent neuroimaging before or after the introduction of the IHS criteria in 1988. RESULTS: There were no differences in the number of CT scans ordered in the period before (6.04%) or after (6.06%) the introduction of the IHS criteria. Only 12 scans revealed significant abnormalities, probably unrelated to headache. CONCLUSIONS: These results suggest that the yield of CT scanning patients seen in a headache clinic is very low, even when alarm signs are present notwithstanding strict adherence to dignostic criteria. An improved definition of secondary forms of headache might help to reduce this adjunctive cost to the care of patients with headache in a headache clinic.

Ambulatory Care Facilities↗
PubMedDate not supplied

[Intracranial hemorrhage studied with a high-field (1.5T) NMR apparatus].

Fifty-two patients were studied with high-field magnetic resonance imaging (1.5T), with T1- and T2-weighted spin-echo pulse sequences. The study was aimed at assessing the efficacy of MR imaging in the evaluation of intracranial hematomas. Characteristic intensity patterns were observed in the evolution of the hematomas, due to the physicochemical changes in hemoglobin. No acute hematomas were observed. In 35 sub-acute hematomas, peripheral hyperintensity could be observed on T1- and T2-weighted pulse sequences. This hyperintensity eventually fills in the hematoma in the chronic stage. In 17 chronic hematomas, a peripheral hypointense ring due to hemosiderin deposits was seen on T1- and T2-weighted scans. The authors conclude that high-field MR imaging is a very sensible diagnostic method in the evaluation of sub-acute and chronic hematomas.

Adult↗