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Biomedical subjects

E Melamed

Publications and source records attributed to E Melamed.

283 records · Page 16Linked to original sources
PubMedDate not supplied

The pharmacokinetic profile of the "first ever" oral dose of levodopa in de novo patients with Parkinson's disease.

To understand the delay in the clinical benefit that commonly occurs after initiation of levodopa (L-Dopa) treatment, we examined the pharmacokinetic profile of L-Dopa after the first oral dose ever taken of L-Dopa/carbidopa in untreated patients with Parkinson's disease and followed these parameters after 1 month of treatment. This was performed in correlation with the clinical therapeutic effect. Plasma levels of L-Dopa were measured with use of high-performance liquid chromatography with electrochemical detection after administration of the "first ever" 125 mg L-Dopa/12.5 mg carbidopa tablet in 15 patients with de novo Parkinson's disease (mean age, 69 +/- 11 y, mean disease duration, 1.5 +/- 0.8 years). Blood samples were drawn before administration and thereafter at various intervals for a period of 4 hours. Repeated measurements after the same oral dose were performed after 1 month of continued therapy with L-Dopa/carbidopa 125/12.5 mg three times daily. Patients were clinically evaluated by unified Parkinson's disease rating scale motor scores. There was a modest clinical improvement after 1 month of continuous L-Dopa treatment (motor scores, 13.1 +/- 11.6 vs. 17.6 +/- 11.7; p < 0.01). Peak plasma L-Dopa levels and area under the curve did not differ significantly between the first-ever dose and after 1 month of continuous treatment (0.9 +/- 0.1 vs. 1.0 +/- 0.1 microg/mL and 66.0 +/- 30.9 vs. 86.2 +/- 34.9 microg/mL, respectively; p < 0.1. There was also no change in time to peak levels between measurements. Results indicate that the first-ever dose of oral L-Dopa is well absorbed and that pharmacokinetic mechanisms such as reduced absorption of L-Dopa probably do not play a major role in the initial delay in clinical response to oral L-Dopa/carbidopa in patients with Parkinson's disease. The latter phenomena may be linked to central pharmacodynamic mechanisms.

Administration, Oral↗
PubMedDate not supplied

Reduction in regional cerebral blood flow during normal aging in man.

Regional cerebral blood flow (rCBF) was measured by the 133Xenon inhalation method in a selected group of 44 normal non-hospitalized, normotensive subjects aged 19 to 79 years. rCBF was computed as the initial slope index value (ISI). Advancing age was associated with significant reductions in the mean brain and mean hemispheric ISI as well as in individual ISI levels measured from all areas in both hemispheres. Our findings suggest that decline of rCBF is not limited to normal elderly subjects but that it is a progressive phenomenon which begins at an earlier age.

Adult↗
PubMedDate not supplied

The prognostic value of the CT scan in conservatively treated patients with intracerebral hematoma.

Prognostic factors for survival and neurological recovery were assessed in 42 patients with nontraumatic intracerebral hematoma (ICH) diagnosed by CT scan. None underwent surgical evacuation of hematoma. CT scans were used to determine location and volume of ICH and presence or absence of intraventricular hemorrhage (IVH). Only 11 patients (26%) died and 17 patients (40.5%) recovered fully. Mortality was associated with: 1) loss of consciousness as a presenting symptom (63.5% mortality rate versus 13% when there was no loss of consciousness at the onset; p less than 0.01). 2) extension of the bleeding into the ventricular system (45% mortality rate versus 9% when hemorrhages were confined to brain parenchyma; p less than 0.01). 3) location of hematoma in the posterior fossa (mortality rate of 43% versus 23% for intrahemispheric hematomas). Mortality was unaffected by age of patients and size of ICH. Full neurological and functional recovery occurred mainly when estimated volume of hematomas was less than 15 cc and with lobar hematomas regardless of size. In survivors there is CT evidence of complete resolution of ICH. Our data indicates a favourable outcome in a relatively large percentage of patients with ICH treated conservatively and therefore questions the need for surgical evacuation of hematoma.

Adolescent↗
PubMedDate not supplied

The effect of cerebral infarction on the regional cerebral blood flow of the contralateral hemisphere.

Regional cerebral blood flow (rCBF) measurements were performed over the contralateral hemisphere by the 133Xe intracarotid injection method in 20 patients with acute cerebral infarction in the territory of the internal carotid artery. The rCBF was found to be reduced, sometimes remarkably, in all of the patients. The mean reduction was 30 percent to 36 percent from the lowest normal value for the mean age of these patients. In the younger age group (40 to 59) the reduction was greater, 40 percent to 47 percent from the lowest normal value for this age. tthe rCBF depression was not related to cerebral dominance, previous hypertension or arterial PCO2 levels. The occurred in both patients who were fully alert and those with disturbances or consciousness, although it tended to be more diminished in the latter. tit can be assumed that the flow reduction in the nonaffected hemisphere is part of a general phenomenon affecting the entire brain and caused by globally reduced cerebral metabolism.

Acute Disease↗
PubMedDate not supplied

Regional cerebral blood flow response to hypocapnia in the contralateral hemisphere of patients with acute cerebral infarction.

The rCBF response to hypocapnia induced by active short-term hyperventilation was determined in the contralateral hemispheres of ten patients with acute unilateral cerebral infarction. Overall rCBF reduction occurred in only two patients. Regional or widespread abnormal responses to Paco2 reduction manifested as either no change or a paradoxical increase in the rCBF were observed in eight patients. The hemispheric mean rCBF reduction following hypocapnia was diminished as compared with control subjects. Our findings suggest that an impairment of the chemical control of rCBF may occur in the non-infarcted hemisphere during the early period following the onset of cerebral infarction. The pathophysiological mechanisms which may underlie this abnormal rCBF reactivity to Paco2 reduction are considered.

Acute Disease↗
PubMedDate not supplied

Direct evidence for absence of beta-adrenergic receptors in rat cerebral vessels histochemical study with a fluorescent beta-blocker.

A fluorescent marker for beta-adrenergic receptor sites, 9-amino-acridin propranolol (9-AAP), was administered intravenously to rats. In contrast to other tissues which are known to contain beta-adrenergic receptors, 9-AAP fluorescence was not observed in the walls of the pial as well as parenchymal cerebral vessels. These negative findings strongly suggest that in the rat, beta-adrenergic receptors are not present in the cerebral vasculature. The role of the alpha-adrenergic receptors needs more study.

Animals↗
PubMedDate not supplied

Parkinson Psychosis Rating Scale: a practical instrument for grading psychosis in Parkinson's disease.

The Parkinson Psychosis Rating Scale (PPRS) was designed to assess the severity of specific symptoms of levodopa-induced psychosis in patients with Parkinson's disease. The scale is administered by the clinician and consists of six items, each rated from 1 (no symptoms) to 4 (extreme symptoms); total score ranges from 6-24 points. To test its reliability, validity, and stability, the authors administered the PPRS to 29 patients with parkinsonian psychosis before and after a 6-week course of treatment with the 5HT3 antagonist ondansetron. Each patient and their caregivers were interviewed by three raters. Results were compared with two other available psychotic symptom scales and one cognitive scale given to the same patients. It was found that the interrater reliability for the total PPRS scores and for each of the individual items was high (Spearman's rho = 0.80-0.99). A significant reduction in PPRS scores was obtained after ondansetron administration, concomitant with a decrease in the Global Functional Impairment score, which was assessed by the family. The changes in PPRS scores occurred irrespective of cognitive dysfunction, as measured by the Minimental State Examination. It appears that the PPRS is a relevant, reliable, valid, and easily-administered instrument for measuring the severity of parkinsonian psychosis. Further studies are needed to evaluate its utility in other organic psychoses and in the assessment of additional pharmacologic treatments for levodopa-induced psychosis.

Aged↗