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Biomedical subjects

J Duarte

Publications and source records attributed to J Duarte.

At least 55 records · Page 3Linked to original sources

Screening Parkinson's disease: a validated questionnaire of high specificity and sensitivity.

A questionnaire designed to screen Parkinson's disease (PD) in literate populations has been developed. It consists of nine questions, self-administered at medical facilities or by mail, and a scale of weights for ascribing scores to specific questions when the answer is positive. The questions were chosen to be symptom specific for PD and the weights were determined from answers provided by 37 PD patients in a neurological outpatient clinic. The questionnaire sensitivity was tested on a different PD population from the same outpatient clinic--50 individuals--and the specificity on a group of 100 ophthalmological patients. The sensitivity was 100% and the specificity was 100%. Three individuals who screened positive among the 100 ophthalmological patients were assessed and given a new diagnosis of PD. This questionnaire therefore constitutes an instrument that should prove valuable as the first stage of a door-to-door survey. It has high sensitivity and specificity.

Adult↗

Association between the oxidative polymorphism and early onset of Parkinson's disease.

The frequency of five cytochrome P450IID6 allelic variants was studied in deoxyribonucleic acid from 123 patients with Parkinson's disease and 150 healthy volunteers. This was achieved by the use of mutation-specific polymerase chain reaction and restriction fragment length polymorphism. The analyses of the CYP2D6 genotype revealed no evidence for a higher prevalence of poor metabolizers among patients with Parkinson's disease. However, increased frequency of patients with Parkinson's disease with the genotype CYP2D6wt/CYP2D6B was observed. This is attributable exclusively to subjects with early onset of the disease (28 to 49 years), with a relative risk ratio of 4.16 (95% confidence limits, 2.0 to 8.3; p < 0.0005). The subjects who had late-onset Parkinson's disease (> or = 50 years) had genotypes and CYP2D6 allele frequencies similar to the healthy subjects. This indicates that the oxidative polymorphism is related to early-onset but not to late-onset Parkinson's disease. A different influence of CYP2D6 genotype on the risk of development of Parkinson's disease is observed in Spaniards, compared with previous findings in British subjects. These results suggest the combined effect of environmental toxins and CYP2D6 in the cause of Parkinson's disease.

Adult↗

Aggravation of parkinsonian tremor by cisapride.

Cisapride, a substituted piperidinyl benzamide that is chemically related to metoclopramide, is a prokinetic agent that facilitates motility of the gastrointestinal tract (1). The mechanism by which cisapride exerts its actions is not clear. It enhances acetylcholine release in the myenteric plexus of the gut, and evidence exists that it has an agonistic action on a serotonin receptor, probably the 5-HT4 receptor (2). The drug is well tolerated, and no central nervous system side effects have been reported. We describe two patients with parkinsonism who experienced aggravation of tremor while on therapy with cisapride.

Aged↗

Changes in cerebral blood flow as monitored by transcranial Doppler during voluntary hyperventilation and their effect on the electroencephalogram.

Hyperventilation results in a fall in carbon dioxide concentration, a fall in cerebral blood flow, and slowing of activity on the electroencephalogram. The temporal relationship and duration of these responses are uncertain, and were investigated using simultaneous monitoring of cerebral blood flow velocity and of the electroencephalograph, with end-tidal carbon dioxide monitoring. Sixteen patients and 9 normal volunteers were studied. Cerebral blood flow velocity in the middle cerebral artery was measured using transcranial Doppler sonography during 3 minutes of hyperventilation and during a 3-minute recovery period. Electroencephalographic recordings were rated by both visual score and measurement of the dominant posterior frequency. End-tidal expired carbon dioxide tension was monitored during the same hyperventilation protocol in the volunteers. Flow velocity fell rapidly during active hyperventilation. Electroencephalographic slowing closely correlated with the decrease in flow velocity (r = 0.86), but lagged behind it. In healthy volunteers capnographic records showed a very tight coupling between end-tidal carbon dioxide concentration and flow velocity (r = 0.94). Three minutes after hyperventilation, carbon dioxide concentration, cerebral blood flow velocity, and electroencephalographic activity were still not back to the resting state. The fall in both cerebral blood flow velocity and carbon dioxide concentration are related to but precede electroencephalographic slowing. The abnormalities persist for at least 3 minutes after hyperventilation and this must be taken into account in clinical electroencephalography. Transcranial Doppler sonography is well suited to monitoring short-term changes in the cerebral circulation.

Adult↗

Inhibitory effects of quercetin and staurosporine on phasic contractions in rat vascular smooth muscle.

The aim of this work was to analyze the effects of quercetin and staurosporine on the phasic contractile responses in rat aorta induced by noradrenaline, 5-hydroxytryptamine (5-HT, serotonin) and caffeine in Ca(2+)-free media. Both quercetin and staurosporine inhibited the contractions induced by 10(-5) M noradrenaline, 10(-5) M 5-HT and 20 mM caffeine in Ca(2+)-free solution. Phorbol 12-myristate 13-acetate (5 x 10(-8) M) enhanced this transient contraction elicited by noradrenaline, an effect that was abolished by quercetin (5 x 10(-5) M). The relaxant effects of quercetin on 80 mM KCl induced contractions were similar in normal and low Na+ solution, e.g. when Ca2+ efflux through the Na+/Ca2+ exchanger was inhibited. Furthermore, quercetin or staurosporine had no effect on 45Ca2+ efflux under resting conditions or when stimulated by 10(-5) M noradrenaline. These results suggested that the inhibitory effects of quercetin and staurosporine on phasic contractile responses induced by receptor agonists in Ca(2+)-free media do not seem to be related to changes in cellular Ca2+ regulation but to an inhibitory effect on the regulation of contractile proteins, an effect probably related to the decreased sensitivity of contractile elements to Ca2+ that apparently resulted from the inhibitory effects of quercetin and staurosporine on protein kinases.

Alkaloids↗

Herpes simplex brainstem encephalitis with a relapsing course.

We report a patient with a relapsing form of acute brainstem encephalitis. Pathological examination demonstrated necrotizing encephalitis in the cerebral cortex and, more pronounced, throughout the diencephalon, as well as in the pes pontis. Neurons and glial cells in the cerebral cortex and brainstem contained herpesvirus antigens. The clinical interrelationship of brainstem encephalitis, Miller Fisher syndrome and Landry-Guillain-Barré syndrome is discussed.

Adolescent↗

Development and clinical assay of the BCM ventricular assist device.

The development of a ventricular assist device is depicted. The seven subprograms that make up the project are described briefly. Results obtained during the clinical assay showed that the new design of the input cannula working as a false auricle provides better efficiency, as well as a certain level of autoregulation for the device.

Aged↗

Vasodilator effects of quercetin in isolated rat vascular smooth muscle.

The effects of quercetin were studied on contractile responses induced by noradrenaline, high KCl, Ca2+ and phorbol 12-myristate,13-acetate in rat aortic strips and on spontaneous mechanical activity in rat portal vein segments. Quercetin, 10(-6)-10(-4) M, inhibited in a concentration-dependent manner the contractions induced by noradrenaline, high KCl and Ca2+, this effect being observed when the drug was added before or after the induced contractions. The spontaneous myogenic portal activity was also inhibited. Mechanical removal of endothelium did not affect the relaxant effects of quercetin on noradrenaline-induced contractions. In addition, at the same range of concentrations, quercetin also relaxed the contractions induced by phorbol 12-myristate,13-acetate. Quercetin1 10(-5) and 5 x 10(-5) M, increased the aortic cyclic AMP content. However, pretreatment with 10(-7) M isoprenaline did not modify the relaxant effects of quercetin on noradrenaline-induced contractions and quercetin did not modify the relaxant effects of forskolin, which suggested that the vasodilator effects of quercetin were not mediated by inhibition of cyclic AMP phosphodiesterases. In conclusion, in isolated rat aorta quercetin produced a vasodilator effect that seems to be mainly related to the inhibition of protein kinase C. However, and since this drug exerts multiple biochemical effects, inhibition of other transduction pathways may be involved in this effect.

Animals↗

Effects of (S)-nafenodone on 45Ca2+ fluxes and contractions in rat isolated vascular smooth muscle.

The effects of (S)-nafenodone, a new antidepressant, were studied on contraction and 45Ca2+ fluxes in rat vascular smooth muscle. In isolated rat aorta (S)-nafenodone, 10(-7) - 10(-4) M, inhibited the contractions induced by 80 mM KCl (IC50 = 1.4 +/- 0.4 x 10(-5) M) and 10(-5) M noradrenaline (IC50 = 1.2 +/- 0.2 x 10(-5) M). (S)-Nafenodone relaxed the contractions induced by both high K+ and noradrenaline, this effect being independent of the presence of functional endothelium. It also inhibited the contractions induced by addition of CaCl2 to Ca(2+)-free high-K+ solution IC50 = 2.5 +/- 0.9 x 10(-6) M) and the phasic contractions induced by noradrenaline in Ca(2+)-free medium, but was a very weak relaxant of the contractions induced by phorbol 12-myristate-13-acetate in Ca2+-free medium. In addition, (S)-nafenodone inhibited the spontaneous mechanical activity in portal vein segments (IC50 = 1.4 +/- 0.8 x 10(-6) M). (S)-Nafenodone inhibited the 45Ca2+ uptake stimulated by high KCl or noradrenaline without altering 45Ca2+ uptake in resting strips and decreased the net 45Ca2+ content in aortic strips non-stimulated as well as stimulated by noradrenaline. In conclusions, (S)-nafenodone inhibited voltage- and agonist-stimulated Ca2+ entry in isolated rat aortas. In addition, it decreased Ca2+ content in both resting and noradrenaline-stimulated muscles, suggesting that it may deplete noradrenaline-sensitive intracellular Ca2+ stores. As a consequence, (S)-nafenodone would reduce the concentration of intracellular free Ca2+ available at the contractile apparatus for vascular smooth muscle contraction.

Animals↗

Vasodilatory effects of flavonoids in rat aortic smooth muscle. Structure-activity relationships.

1. Flavonoids relaxed the contractions induced by noradrenaline, KCl or phorbol 12-myristate, 13-acetate in rat aortic strips, the order of potency being: flavonols (quercetin, kaempferol, pentamethylquercetin) > flavones(luteolin, apigenin) > flavanols((+)-catechin, (-)-epicatechin) which correlates with the reported order of potency to inhibit protein kinase C. 2. The relaxant effects of kaempferol and luteolin were slightly potentiated by isoprenaline and those of pentamethylquercetin, kaempferol and apigenin by sodium nitroprusside. 3. It is concluded that the main vasodilatory mechanism of flavonoids seems to be the inhibition of protein kinase C. Inhibition of cyclic nucleotide phosphodiesterases or decreased Ca2+ uptake may also contribute to their vasodilatory effects.

3',5'-Cyclic-AMP Phosphodiesterases↗