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Biomedical subjects

L Cunha

Publications and source records attributed to L Cunha.

16 recordsLinked to original sources
PubMed2007

Almotriptan and zolmitriptan in the acute treatment of migraine.

OBJECTIVE: To compare almotriptan and zolmitriptan in the treatment of acute migraine. METHODS: This multicentre, double-blind trial randomized adult migraineurs to almotriptan 12.5 mg (n = 532) or zolmitriptan 2.5 mg (n = 530) for the treatment of a single migraine attack. The primary end point was sustained pain free plus no adverse events (SNAE); other end points included pain relief and pain free at several time points, sustained pain free, headache recurrence, use of rescue medication, functional impairment, time lost because of migraine, treatment acceptability, and overall treatment satisfaction. RESULTS: No significant difference was seen in SNAE (almotriptan 29.2% vs zolmitriptan 31.8%) or the other efficacy end points measured. The incidence of triptan-associated AEs and triptan-associated central nervous system AEs was significantly lower for patients receiving almotriptan compared to zolmitriptan. CONCLUSIONS: Almotriptan and zolmitriptan were associated with similar efficacy and overall tolerability in the treatment of acute migraine. Almotriptan was associated with a significantly lower rate of triptan-associated AEs.

Acute Disease↗
PubMed2001

Glycine antagonist (GV150526) in acute stroke: a multicentre, double-blind placebo-controlled phase II trial.

GV150526 is a novel glycine antagonist at the NMDA receptor complex. It is a potent neuroprotective agent in animal models of acute stroke including permanent middle cerebral artery occlusion in the rat. GV150526 was very well tolerated in early human studies. The purpose of this randomised, double-blind, multicentre, placebo-controlled trial was to assess the safety and population pharmacokinetics of GV150526 in patients with a clinical diagnosis of acute stroke. Exploratory assessment of efficacy, quality of life and resource utilisation was also undertaken. Upon clinical diagnosis of acute stroke within 12 h of onset of symptoms, patients were treated with a loading dose of 800 mg GV150526 (or placebo), followed by 5 maintenance doses of 400 mg GV150526 (or placebo) given every 12 h over 3 days. Following observation of asymptomatic hyperbilirubinaemia, the maintenance dose was reduced mid-study to 200 mg. CT/MRI scanning was not mandatory prior to treatment. The study treated 128 patients (38 with GV 800 mg/400 mg, 48 with GV 800 mg/200 mg and 42 with placebo). Fewer patients with mild stroke (NIH scores < or =5) were enrolled in the GV150526-treated groups than in the placebo group (placebo 38%, GV 800 mg/400 mg 18%, GV 800 mg/200 mg 15%). There was also an imbalance in the proportion of patients with haemorrhagic strokes (placebo 5%, GV 800 mg/400 mg 3%, GV 800 mg/200 mg 15%). Mortality at 1 month was unbalanced between treatment groups, being 10, 18 and 17% in the placebo, GV 800 mg/400 mg and GV 800 mg/200 mg groups, respectively (no significant difference). Similarly, adverse events, though consistent with an acute stroke population, appeared more often in the GV 800 mg/200 mg group. Functional outcomes at 1 month also showed imbalances, the percentage of patients with a Barthel Index score of > or =95 at 1 month being 52, 39 and 27% in the placebo, GV 800 mg/400 mg and GV 800 mg/200 mg groups, respectively. These results probably reflect a prognostically significant baseline difference between the groups rather than the effect of GV150526. GV150526 was generally well tolerated in patients with a clinical diagnosis of acute stroke and formal efficacy studies were considered justified.

Aged↗
PubMed1999

Antiplatelet treatment does not reduce the severity of subsequent stroke. European Stroke Prevention Study 2 Working Group.

OBJECTIVE: To assess the the effect of antiplatelet therapy on the severity of subsequent stroke in patients with stroke and TIA. BACKGROUND: The Second European Stroke Prevention Study (ESPS2) recruited 6,602 patients in four treatment groups: placebo, 2 x 25 mg acetylsalicylic acid (ASA), 2 x 200 mg dipyridamole (DP), and the combination of 50 mg ASA and 400 mg DP per day. Seventy-six percent of the patients had had a stroke as the qualifying event, whereas 24% had a TIA. All patients were followed at 3-month intervals for 2 years. ESPS2 showed a benefit from antiplatelet treatment compared with placebo and an additional benefit using ASA and DP together compared with either of these antiplatelet agents alone. METHODS: In the ESPS2, the study protocol included assessment of severity of end point stroke with the modified Rankin scale once the stroke had clinically stabilized, and no further impairment was observed. There were 824 new stroke events during follow-up. In 701 of them, the initial Rankin scale was known, and this was also evaluated after each nonfatal recurrent stroke. The difference in Rankin scale between treatment groups was analyzed after recurrent stroke, and the progress in Rankin scale between entry and recurrent stroke was quantified by calculating the number of patients with a change of one or more degrees in the scale. RESULTS: There were no significant differences in these changes in Rankin scale between the treatment groups. The mean time to reach an end point of stroke was longest in patients who used ASA + DP (p = 0.057). However, there was no difference among the treatment groups in the time to death during follow-up. CONCLUSION: This study suggests that antiplatelet therapy does not influence the severity of recurrent stroke as evaluated with the Rankin scale. However, antiplatelet therapy seems to lengthen the time the patient remains free from a recurrent stroke.

Aged↗
PubMed1999

Second European Stroke Prevention Study: antiplatelet therapy is effective regardless of age. ESPS2 Working Group.

BACKGROUND: The Second European Stroke Prevention Study (ESPS2) was a randomized, placebo-controlled trial that investigated the efficacy of low-dose acetylsalicylic acid (ASA) and modified-release dipyridamole (DP), alone or in combination, in the secondary prevention of ischemic stroke. The trial demonstrated that the combination was significantly more effective than either agent used alone. The aim of the present study was to evaluate the influence of age on the efficacy of ASA and DP, alone or in combination, in the secondary prevention of stroke in the ESPS2 population. METHODS AND RESULTS: A total of 6602 patients were recruited to the ESPS2 and there were 4 treatment groups: ASA (25 mg twice daily), DP (200 mg twice daily), ASA and DP in a combined formulation, or placebo. Primary endpoints were stroke, death, and stroke or death together. The endpoints evaluated in the present study were stroke, stroke and/or death, and vascular events. Stroke was the qualifying event in 76% of the patients, while 24% had a transient ischaemic attack. Patients were reviewed at 3-month intervals for 2 years. The study population consisted of 2565 (39%) patients aged less than 65 years, 2240 (34%) patients aged between 65 and 74 years, and 1797 (27%) patients aged 75 years and over. Advancing age was associated with an increased incidence of endpoints in all 4 treatment groups. The combination of ASA and DP significantly reduced the incidence of all endpoints, compared with placebo, in each age group. There was no influence of age on the efficacy of antiplatelet therapy for any of the evaluated endpoints. Relative risk reductions of treatment compared with placebo were 11.1-27.6% in the ASA group, 8.0-18.7% in the DP group, and 20.3-45.2% in patients receiving combination therapy. CONCLUSION: This study clearly demonstrates that combination therapy with DP and ASA is superior to either agent used alone in the secondary prevention of ischemic stroke, irrespective of the age of the patient.

Administration, Oral↗
PubMed1996

European Stroke Prevention Study. 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke.

In 1988, we undertook a randomized, placebo-controlled, double-blind trial to investigate the safety and efficacy of low-dose acetylsalicylic acid (ASA), modified-release dipyridamole, and the two agents in combination for secondary prevention of ischemic stroke. Patients with prior stroke or transient ischemic attack (TIA) were randomized to treatment with ASA alone (50 mg daily), modified-release dipyridamole alone (400 mg daily), the two agents in a combined formulation, or placebo. Primary endpoints were stroke, death, and stroke or death together. TIA and other vascular events were secondary endpoints. Patients were followed on treatment for two years. Data from 6,602 patients were analysed. Factorial analysis demonstrated a highly significant effect for ASA and for dipyridamole in reducing the risk of stroke (p < or = 0.001) and stroke or death combined (p < 0.01). In pairwise comparisons, stroke risk in comparison to placebo was reduced by 18% with ASA alone (p = 0.013); 16% with dipyridamole alone (p = 0.039); and 37% with combination therapy (p < 0.001). Risk of stroke or death was reduced by 13% with ASA alone (p = 0.016); 15% with dipyridamole alone (p = 0.015); and 24% with the combination (p < 0.001). The treatment had no statistically significant effect on the death rate alone. Factorial analysis also demonstrated a highly significant effect of ASA (p < 0.001) and dipyridamole (p < 0.01) for preventing TIA. The risk reduction for the combination was 36% (p < 0.001) in comparison with placebo. Headache was the most common adverse event, occurring more frequently in dipyridamole-treated patients. All-site bleeding and gastrointestinal bleeding were significantly more common in patients who received ASA in comparison to placebo or dipyridamole. We conclude that (1) ASA 25 mg twice daily and dipyridamole, in a modified-release form, at a dose of 200 mg twice daily have each been shown to be equally effective for the secondary prevention of ischemic stroke and TIA; (2) when co-prescribed the protective effects are additive, the combination being significantly more effective than either agent prescribed singly; (3) low-dose ASA does not eliminate the propensity for induced bleeding.

Adult↗
PubMed1993

Glutamate dehydrogenase deficiency in Machado-Joseph disease.

We studied the activity of glutamate dehydrogenase (GDH) in leukocytes from 23 patients with dominantly inherited ataxia. All the patients were assessed with a rating scale for ataxias and met the clinical criteria for the diagnosis of Machado-Joseph disease. The mean age of onset of symptoms was 37.8, SD 13.4 years and the duration of the disease was 7.4, SD 4.9. Leukocyte GDH activity was significantly decreased (p < 0.001) when compared to 20 normal controls. These data extend previous reports indicating that a GDH deficiency is present in peripheral tissues from some patients with spinocerebellar degenerations. Furthermore, this study suggests that a genetic deficiency of GDH may underlie some forms of dominant ataxias; this deficiency may be marked in patients with Machado-Joseph disease and is not specific for any type of multiple system atrophy.

Adolescent↗
PubMed1988

Dominantly inherited ataxias in Portugal.

We analysed the clinical features of 82 patients with dominantly inherited ataxia in a cohort survey. All patients fulfilled the diagnostic criteria for Machado-Joseph disease. The mean age of onset of symptoms was 39.8 (+/- 12.5) years and the duration of the disease was 9.2 (+/- 6.7) years. Ataxia, peripheral neuropathy, and fasciculation scores correlated with age of onset and duration of disease. Upper motor neuron scores failed to correlate with age of onset. In a follow-up study we analysed the clinical data of 46 patients two years after the first examination. A paired t-test was used to compare differences between observations. The results are in agreement with those of the cross-section in time, suggesting a deterioration of the symptoms with the evolution of the disease. We conclude that dynamic definition of the disease according to age of onset and duration of symptoms is preferable to subdivision into classical types.

Adult↗
PubMed1986

[2 cases of stiff-man syndrome with tremor].

Clinical history, neurologic investigations, course, EMG findings, muscle biopsy and response to diazepam treatment in two patients fulfilled criteria established by Gordon, Januszko and Kaufman for the diagnosis of the stiff-man syndrome. Both patients also presented tremor, a rare finding in this affection.

Contracture↗
PubMed1984

The natural history of Machado-Joseph disease. An analysis of 138 personally examined cases.

We have examined 138 cases of a disorder previously described in people of Portuguese origin and which has received many names. By computer analysis of 46 different items of a standardized neurological examination carried out in each patient, we have been able to delineate the main components of the clinical presentation, to conclude that the marked variability in clinical expressions does not negate the homogeneity of the disorder, and to describe the natural history of this entity which should be called, for historical reasons, "Machado-Joseph Disease". This hereditary disease has an autosomal dominant pattern of inheritance, presenting as a progressive ataxia with external ophthalmoplegia, and should be classified within the group of "Ataxic multisystem degenerations". When the disease starts before the age of 20, it may present with marked spasticity, of a non progressive nature but often so severe that it can be accompanied by "Gegenhalten" countermovements and dystonic postures but little frank dystonia. There are few true extrapyramidal symptoms except akinesia. When the disease starts after the age of 50, the clinical spectrum is mostly that of an amyotrophic polyneuropathy with fasciculations accompanying the ataxia. For all the other cases the clinical picture is a continuum between these two extremes, the main determinant of the clinical phenotype being the age of onset and a secondary factor, the place of origin of the given kindred. The ataxic and amyotrophic components are clearly progressive with time in contrast to the spasticity component. Although the majority of known cases are of Portuguese origin, this is not obligatory. The next research endeavour should be a search for the chromosomal site of the gene, using molecular biology technology such as those for recombinant DNA.

Adolescent↗
PubMed1981

Homovanilic acid in Huntington's disease and Sydenham's chorea.

Homovanilic acid (HVA) was determined in the lumbar CSF of 12 patients with Huntington's disease and 12 with Sydenham's chorea before and after probenecid administration. The means of HVA concentration (basal and after probenecid) were lower in those with Huntington's disease than in controls, and were even lower in a sub-group characterised by increased tone and slowness of voluntary movement. There was no correlation between CSF HVA values and the severity of abnormal movements, nor with length of the illness and age of the patients with Huntington's disease. The mean basal HVA concentration did not differ from controls in those with Sydenham's chorea but the accumulation with probenecid was significantly lower. These results suggest a decrease in cerebral dopamine release in both forms of chorea.

Adult↗
PubMedDate not supplied

Acute intermittent porphyria: novel missense mutations in the human hydroxymethylbilane synthase gene.

PURPOSE: To identify mutations in families with acute intermittent porphyria, an autosomal dominant inborn error of metabolism that results from the half-normal activity of the third enzyme in the heme biosynthetic pathway, hydroxymethylbilane synthase. METHODS: Mutations were identified by direct solid phase sequencing. RESULTS: Two novel missense mutations E80G and T78P and three previously reported mutations, R173W, G111R, and the splice site lesion, IVS1+1, were detected, each in an unrelated proband. The causality of the novel missense mutations was demonstrated by expression studies. CONCLUSION: These findings provide for the precise diagnosis of carriers in these families and further expand the molecular heterogeneity of AIP.

Amino Acid Substitution↗