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Biomedical subjects

João Costa

Publications and source records attributed to João Costa.

At least 19 recordsLinked to original sources
PubMed2006

Motor responses of muscles supplied by cranial nerves to subthalamic nucleus deep brain stimuli.

The distribution of human corticobulbar motor excitatory and inhibitory output is not fully understood. In particular, it is unclear whether the pattern of innervation is the same for upper and lower facial muscles, and what is the motor cortical area giving rise to such innervation. We used electrodes implanted in the subthalamic nucleus (STN) in patients with Parkinson's disease to activate motor tracts at a subcortical level. We examined the excitatory and inhibitory effects of unilateral single STN deep brain stimulation (sSTN-DBS) in 14 patients by taking recordings from facial, cervical and upper limb muscles on both sides. We measured the latency and amplitude of the motor-evoked potentials (MEPs), and the latency and duration of the silent periods, and compared ipsilateral with contralateral responses and responses obtained in different muscles. Unilateral sSTN-DBS induced strictly contralateral MEPs in the trapezius, deltoid, biceps and thenar muscles. The same stimulus always induced bilateral MEPs in the orbicularis oculi, orbicularis oris, masseter and sternocleidomastoid at a mean latency in the range 6.0-9.1 ms. MEP latencies in the orbicularis oculi and orbicularis oris were significantly longer than in the masseter and sternocleidomastoid (P < 0.01). A short latency small action potential was recorded in the ipsilateral orbicularis oculi that was likely generated by activation of extraocular muscles. During sustained voluntary muscle contraction, a silent period was recorded at similar onset latency on both sides. This period was significantly shorter in orbicularis oculi than in masseter, and in the ipsilateral side for both muscles (P < 0.01). sSTN-DBS is able to activate the descending projecting fibres in the corticobulbar tract eliciting bilateral MEPs and silent periods in facial and cranial muscles. This suggests that fibres to both ipsi- and contralateral motor nuclei descend together at the level of the STN. These findings are relevant in the discussion of the innervation of upper and lower facial muscles in humans and in the interpretation of previous results obtained with transcranial cortical stimulation.

Aged↗
PubMed2006

Single subthalamic nucleus deep brain stimuli inhibit the blink reflex in Parkinson's disease patients.

The disordered output from the basal ganglia to the pontine tegmentum nuclei is considered responsible for a number of abnormalities in brainstem reflexes in patients with Parkinson's disease. One of the most conspicuous of these abnormalities is the reduced inhibition of the blink reflex by a prepulse stimulus. The circuit of prepulse inhibition involves structures and fibre groups that can be reached by stimuli applied through the electrodes implanted in the subthalamic nucleus for deep brain stimulation (STNDBS). In seven Parkinson's disease patients we examined whether single STNDBS induced prepulse effects on the blink reflex and how they compared with the effects induced by single auditory and somatosensory stimuli. Prepulse inhibition was determined by measuring the percentage inhibition induced in the R2 component of the orbicularis oculi response to supraorbital nerve stimuli. The inter-stimuli intervals (ISI) between the prepulse and the supraorbital nerve stimuli were 0 to 30 ms and 100 ms for single STNDBS and 100 ms for auditory and somatosensory modalities. The results obtained with acoustic and somatosensory stimuli were compared with those obtained from a group of 20 age-matched healthy subjects. Single STNDBS induced significant inhibition of the R2 in all patients at ISIs between 10 and 30 ms, with a mean percentage inhibition of 94% at the ISI of 30 ms. On the contrary, significant inhibition by auditory or somatosensory stimuli was induced in only two out of the seven patients. The mean percentage inhibition at the ISI of 100 ms was 37% for auditory and 40% for somatosensory stimuli, well below reference limits for prepulse inhibition in control subjects (61%). Single STNDBS induces significant prepulse inhibition of the blink reflex in Parkinson's disease patients who have abnormally reduced auditory and somatosensory prepulse effects. This finding helps define the prepulse circuit in humans and the eventual site of its dysfunction in Parkinson's disease.

Acoustic Stimulation↗
PubMed2006

Efficacy of lipid lowering drug treatment for diabetic and non-diabetic patients: meta-analysis of randomised controlled trials.

OBJECTIVE: To evaluate the clinical benefit of lipid lowering drug treatment in patients with and without diabetes mellitus, for primary and secondary prevention. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Cochrane, Medline, Embase, and reference lists up to April 2004. STUDY SELECTION: Randomised, placebo controlled, double blind trials with a follow-up of at least three years that evaluated lipid lowering drug treatment in patients with and without diabetes mellitus. DATA EXTRACTION: Two independent reviewers extracted data. The primary outcome was major coronary events defined as coronary heart disease death, non-fatal myocardial infarction, or myocardial revascularisation procedures. RESULTS: Twelve studies were included. Lipid lowering drug treatment was found to be at least as effective in diabetic patients as in non-diabetic patients. In primary prevention, the risk reduction for major coronary events was 21% (95% confidence interval 11% to 30%; P < 0.0001) in diabetic patients and 23% (12% to 33%; P = 0.0003) in non-diabetic patients. In secondary prevention, the corresponding risk reductions were 21% (10% to 31%; P = 0.0005) and 23% (19% to 26%; P < or = 0.00001). However, the absolute risk difference was three times higher in secondary prevention. When results were adjusted for baseline risk, diabetic patients benefited more in both primary and secondary prevention. Blood lipids were reduced to a similar degree in both groups. CONCLUSIONS: The evidence that lipid lowering drug treatment (especially statins) significantly reduce cardiovascular risk in diabetic and non-diabetic patients is strong and suggests that diabetic patients benefit more, in both primary and secondary prevention. Future research should define the threshold for treatment of these patients and the desired target lipid concentrations, especially for primary prevention.

Coronary Disease↗
PubMed2006

Transient left ventricular apical ballooning.

We describe the case of an elderly woman patient referred for primary angioplasty for acute anterior myocardial infarction, which developed after intense emotional stress. The coronary angiogram was surprisingly normal, but left ventriculography showed severe apical dilatation and dyskinesia, confirmed by echocardiography. By this time we suspected a syndrome of transient apical ballooning without coronary stenosis, which mimics acute myocardial infarction. She underwent medical therapy and subsequent clinical evolution was favorable, with complete recovery of left ventricular systolic function. We discuss the clinical setting and the pathophysiologic mechanisms of this syndrome.

Aged↗
PubMed2005

Pain and calf hypertrophy associated with spontaneous repetitive discharges treated with botulinum toxin.

OBJECTIVE: To report a case of neurogenic calf hypertrophy associated with root lesion responsive to botulinum toxin (BTX). In addition, we systematically review the literature for cases of muscle hypertrophy associated with radiculopathy. METHODS: A 56-year-old man with a previous history of S1 root lesion presented with marked calf hypertrophy, muscle pain, cramps, fasciculations, and increased CK level. Magnetic resonance imaging and muscle biopsy confirmed true muscle hypertrophy. Electromyography (EMG) showed signs of chronic denervation-reinnervation in the right S1 myotome, with greatly increased spontaneous activity (SA) (fasciculations and complex repetitive discharges). Botox(R) was injected in 3 occasions on 4 sites on the right gastrocnemius (20U per site). Symptoms, CK level and SA on EMG (quantified) were evaluated. RESULTS: The patient improved clinically, CK level and SA steadily decreased. CONCLUSIONS: The literature review failed to identify a unique causative factor for muscle hypertrophy related to neurogenic lesions. BTX treatment was effective in our patient with muscle hypertrophy associated with SA. SIGNIFICANCE: We provide further evidence that spontaneous activity secondary to nerve lesion may cause focal muscle hypertrophy. Treatment with BTX should be considered in these conditions.

Anti-Dyskinesia Agents↗
PubMed2005

Clinical trials in ALS: a review of the role of clinical and neurophysiological measurements.

We have reviewed all the published clinical trials of ALS and, from those considered sufficiently large, and containing a control group, we have evaluated their methodology with regard to statistical power. This implies a critical analysis of the endpoint measurements. We have concluded that clinical endpoints used in clinical trials of ALS have frequently been insufficiently sensitive, non-linear, or even not intuitively highly relevant to the disease. We suggest that the ALS-FRS, perhaps also MUNE and the Neurophysiological Index, may be the best measures currently available. These techniques have complementary characteristics that allow them to be used to address different aspects of the disease and its treatment in various trials designs. In the past some trials may have failed to demonstrate a treatment effect because the chosen endpoint measures and the trial design were inappropriate.

Amyotrophic Lateral Sclerosis↗
PubMed2004

Clinical comparability of marketed formulations of botulinum toxin.

The majority of pharmaceutical products are patented in early phases of their discovery to preclude competition by similar products. Due to unusual circumstances (botulinum toxin is an unpatentable natural product and it is considered to be a biological weapon), technology know-how for botulinum toxin production was classified rather then available in the scientific community. Botulinum toxin type A was marketed in two pharmaceutical distinct formulations from competitor companies. Serendipity proved that the two formulations were not equipotent in terms of mouse units. From a regulatory point of view, differences in potency of distinct formulations are not a matter of concern because each formulation is licensed based on its own set of data. As far as the data in each case is sufficient to prove that a particular formulation is safe and efficacious at its defined dosage, a license for use can be granted. On the other hand, generation of data on comparability is the only way that clinicians and managers can ascertain which product (formulation, serotype) is most cost-effectiveness and to determine whether there are relevant differences in their safety profiles. The results of the systematic review of head-to-head randomised trials comparing BOTOX to Dysport suggest that the two formulations are not bioequivalent whatever the dose relationship. Data on comparative immunogenicity are not available. The indirect comparison of the results obtained in randomised clinical trials comparing BOTOX to placebo and Dysport to placebo support that intrinsic differences are present in the two products. It is concluded that comparative economic evaluations of different botulinum toxin formulations should move away from cost-minimization approaches based on the presumption of bioequivalence and move toward cost-effectiveness or cost-utility models.

Aged↗
PubMed2004

Repetitive nerve stimulation in myasthenia gravis--relative sensitivity of different muscles.

OBJECTIVE: To correlate repetitive nerve stimulation (RNS) decrement in different muscles with the predominant clinical presentation in myasthenia gravis (MG), and to study single fibre EMG (SFEMG) sensitivity in ocular MG. METHODS: Sixty-nine, untreated, consecutive patients suspected for MG were observed prospectively for a minimum of 6 months. Those who improved on medical treatment were diagnosed as MG. The others, in whom the neurophysiological studies were normal and that did not improve on medical treatment served as a control group, from which normative data for RNS and SFEMG was obtained. The MG patients were further classified in 3 subgroups according to the predominant clinical presentation: group I (ocular); group b (bulbar); and group a (axial). We performed RNS in nasalis, trapezius, anconeus, and abductor digiti minimi. All patients with ocular MG underwent jitter determination of the orbicularis oculi muscle. RESULTS: Thirty-seven patients were diagnosed as MG (group I, 15; group b, 13; group a, 9). In group I, RNS was abnormal in 33% of the patients. RNS studies disclosed at least one abnormal muscle response in every patient in groups a and b. Trapezius was significantly more sensitive in group a, and anconeus and nasalis in group b (P < 0.01). Jitter was abnormal in all patients in group I, and the most sensitive parameter was an increased number of unstable pairs, 100%. CONCLUSIONS: Based on these observations, we recommend that a shoulder muscle, as the trapezius, should be studied first in the limb-axial presentation of MG, and the anconeus-nasalis muscles in predominant bulbar MG. In ocular MG, RNS is not sensitive and jitter should be performed in facial muscles. SIGNIFICANCE: This paper shows the unequal sensitivity of several muscles to RNS in different forms of MG.

Adult↗
PubMed2004

Statins for primary and secondary prevention of coronary heart disease. A scientific review.

Cardiovascular disease has an elevated prevalence in the general population, with increasing incidence with advancing age. Epidemiological studies clearly show that higher concentrations of serum lipids (especially cholesterol) constitute a major individual risk factor, and that their treatment reduces the incidence of cardiovascular disease, especially coronary heart disease (CHD). The best evidence supporting the importance of hypercholesterolemia as a major risk factor for CHD arises from large randomized controlled trials (RCTs), which show that by lowering total cholesterol and low-density lipoprotein concentrations, and increasing high-density lipoprotein concentrations, coronary event rates and cardiovascular mortality are diminished. Also, hyperlipidemia is frequently found in patients suffering from premature CHD and, in most cases, has a familial genetic component. The benefit from lowering cholesterol is found in primary prevention (patients with hypercholesterolemia but no known CHD), as well as in secondary prevention (patients with known CHD, in whom the aim is to improve prognosis). The main objective of this paper is to present and discuss the most valid, important and applicable scientific evidence on the primary and secondary prevention of coronary heart disease using statins. We have based our discussion on large RCTs that studied clinically relevant outcomes (mortality, morbidity, event rates, etc.), published over the last 10 years, as well as on systematic reviews and/or meta-analyses of RCTs published over the last 5 years. Both types of evidence were selected from secondary scientific sources. We conclude with practical evidence-based recommendations on the selection of patients for primary and secondary prevention with statins.

Anticholesteremic Agents↗
PubMed2004

Burden of disease from hypercholesterolemia in Portugal.

Cardiovascular diseases are the main cause of death in Portugal, in developed countries and indeed, worldwide. Hypercholesterolemia is a major risk factor for these diseases. What are the potential health gains to be obtained by reducing the prevalence of hypercholesterolemia in the Portuguese population? How are they to be estimated and quantified? Studies of the burden of disease aim to measure and evaluate the impact of a disease or group of diseases on overall levels of health. Although they do not strictly speaking constitute an economic evaluation, since no specific interventions are analyzed, burden of disease studies do provide an accurate picture of a specific health problem and its magnitude, as well as an indication of changes in health policy and in preventive or corrective measures that might lead to improvement. This paper reports the results of a study of the disease burden of hypercholesterolemia in Portugal, calibrated for data from the year 2000. In this study, the disease burden is estimated as the component attributable to hypercholesterolemia in DALYs (disability-adjusted life years). DALYs are a measure used by international organizations such as the World Health Organization and the World Bank.

Adolescent↗
PubMed2003

Incidence and prevalence of hypercholesterolemia in Portugal: a systematic review. Part I.

INTRODUCTION: Over 50% of the mortality and disability caused by ischemic heart disease and stroke could be avoided by controlling individual risk factors (hypertension, hypercholesterolemia, smoking and obesity). The ignorance of the extent and impact of hypercholesterolemia (HC) in Portugal prompted us to undertake this systematic review of the prevalence and incidence of hyperlipidemia in Portugal, based exclusively on work published nationally. METHODS: We included every study published in the country that could provide data on the prevalence or incidence of hypercholesterolemia. The search strategy included an electronic search of national and international biomedical databases (Medline, Index Revistas Médicas Portuguesas, the Portuguese Directorate-General for Health and the Portuguese National School of Public Health), screening of reference lists from the individual studies, and personal contacts with institutions, groups and authors (such as the Portuguese Foundation of Cardiology). The data--recorded in electronic format--was collected independently by two of the authors (JC and MB), with consensus achieved with a third (AVC) when there were differences in the study coding. RESULTS: We could only identify one paper on the incidence of HC in Portugal, which gave an incidence of 559 new cases per 100,000 inhabitants, increasing with age up to 54 years for men and 64 years for women. There was a higher incidence in men than in women up to the age of 54, but at more advanced ages this relationship was reversed. Prevalence studies on HC included 53,445 individuals overall, with sample size lower than 1000 in most of the individual studies. The most frequently used criterion for HC was > 200 mg/dL, with the mean level being higher in most studies. We calculated the mean prevalence for several cut-off points (190 mg/dL: 63.8%; 200 mg/dL: 56.7%; 240 mg/dL: 31.7%; 250 mg/dL: 21%). Due to the heterogeneity of the data, these results are to be interpreted with caution, even though they are consistent across individual studies. The prevalence of hypertriglyceridemia (HTG) was highly variable across studies. Most of them used a baseline criterion of 150 mg/dL (11-26%) or 200 mg/dL (8.9-33.9%). CONCLUSIONS: Despite the obvious heterogeneity and a certain paucity of studies, we found consistent results concerning the prevalence of hypercholesterolemia in Portugal, and we can state that this constitutes a serious health problem in our country. The prevalence of hypercholesterolemia was higher than that of arterial hypertension in our population. The results of this study should serve as a basis for a commitment to action from the health authorities and health professionals as well as patients.

Humans↗
PubMed2003

Incidence and prevalence of hypercholesterolemia in Portugal: a systemic review. Part II.

INTRODUCTION: Over 50% of the mortality and disability caused by ischemic heart disease and stroke could be avoided by controlling individual risk factors (hypertension, hypercholesterolemia, smoking and obesity). The ignorance of the extent and impact of hypercholesterolemia (HC) in Portugal prompted us to undertake this systematic review of the prevalence and incidence of hyperlipidemia in Portugal, based exclusively on work published nationally. METHODS: We included every study published in the country that could provide data on the prevalence or incidence of hypercholesterolemia. The search strategy included an electronic search of national and international biomedical databases (Medline, Index Revistas Médicas Portuguesas, the Portuguese Directorate-General for Health and the Portuguese National School of Public Health), screening of reference lists from the individual studies, and personal contacts with institutions, groups and authors (such as the Portuguese Foundation of Cardiology). The data--recorded in electronic format--was collected independently by two of the authors (JC and MB), with consensus achieved with a third (AVC) when there were differences in the study coding. RESULTS: We could only identify one paper on the incidence of HC in Portugal, which gave an incidence of 559 new cases per 100,000 inhabitants, increasing with age up to 54 years for men and 64 years for women. There was a higher incidence in men than in women up to the age of 54, but at more advanced ages this relationship was reversed. Prevalence studies on HC included 53,445 individuals overall, with sample size lower than 1000 in most of the individual studies. The most frequently used criterion for HC was > 200 mg/dL, with the mean level being higher in most studies. We calculated the mean prevalence for several cut-off points (190 mg/dL: 63.8%; 200 mg/dL: 56.7%; 240 mg/dL: 31.7%; 250 mg/dL: 21%). Due to the heterogeneity of the data, these results are to be interpreted with caution, even though they are consistent across individual studies. The prevalence of hypertriglyceridemia (HTG) was highly variable across studies. Most of them used a baseline criterion of 150 mg/dL (11-26%) or 200 mg/dL (8.9-33.9%). CONCLUSIONS: Despite the obvious heterogeneity and a certain paucity of studies, we found consistent results concerning the prevalence of hypercholesterolemia in Portugal, and we can state that this constitutes a serious health problem in our country. The prevalence of hypercholesterolemia was higher than that of arterial hypertension in our population. The results of this study should serve as a basis for a commitment to action from the health authorities and health professionals as well as patients.

Humans↗
PubMed2003

Incidence and prevalence of hypercholesterolemia in Portugal: a systematic review. Part III.

INTRODUCTION: Over 50% of the mortality and disability caused by ischemic heart disease and stroke could be avoided by controlling individual risk factors (hypertension, hypercholesterolemia, smoking and obesity). The ignorance of the extent and impact of hypercholesterolemia (HC) in Portugal prompted us to undertake this systematic review of the prevalence and incidence of hyperlipidemia in Portugal, based exclusively on work published nationally. METHODS: We included every study published in the country that could provide data on the prevalence or incidence of hypercholesterolemia. The search strategy included an electronic search of national and international biomedical databases (Medline, Index Revistas Médicas Portuguesas, the Portuguese Directorate-General for Health and the Portuguese National School of Public Health), screening of reference lists from the individual studies, and personal contacts with institutions, groups and authors (such as the Portuguese Foundation of Cardiology). The data--recorded in electronic format--was collected independently by two of the authors (JC and MB), with consensus achieved with a third (AVC) when there were differences in the study coding. RESULTS: We could only identify one paper on the incidence of HC in Portugal, which gave an incidence of 559 new cases per 100,000 inhabitants, increasing with age up to 54 years for men and 64 years for women. There was a higher incidence in men than in women up to the age of 54, but at more advanced ages this relationship was reversed. Prevalence studies on HC included 53,445 individuals overall, with sample size lower than 1000 in most of the individual studies. The most frequently used criterion for HC was > 200 mg/dL, with the mean level being higher in most studies. We calculated the mean prevalence for several cut-off points (> or = 190 mg/dL: 63.8%; > or = 200 mg/dL: 56.7%; > or = 240 mg/dL; 31.7%; > or 250 mg/d; 21%). Due to the heterogeneity of the data, these results are to be interpreted with caution, even though they are consistent across individual studies. The prevalence of hypertriglyceridemia (HTG) was highly variable across studies. Most of them used a baseline criterion of 150 mg/dL (11-26%) or > or = 200 mg/dL (8.9-33.9%). CONCLUSIONS: Despite the obvious heterogeneity and a certain paucity of studies, we found consistent results concerning the prevalence of hypercholesterolemia in Portugal, and we can state that this constitutes a serious health problem in our country. The prevalence of hypercholesterolemia was higher than that of arterial hypertension in our population. The results of this study should serve as a basis for a commitment to action from the health authorities and health professionals as well as patients.

Humans↗
PubMed2002

Evidence-based medicine (EBM) applied to Parkinson's disease treatment.

This paper is a narrative review of the concept of evidence-based medicine (EBM) and its application in the movement disorders field. The paper has three parts: 1. Discussion of the generic concept of EBM and of the most commonly voiced criticisms; explanation of how relevant are for the comprehension of EBM procedures the notion of implicit and explicit knowledge; discussion of the scientific basis of the hierarchical organization of the evidence and the recent challenges to it; the different robustness of data pertaining to efficacy and to safety. 2. Accessibility of the evidence relevant for the treatment of Parkinson disease. Description of the most relevant tools to bring unbiased data to the hands of the practicing physician; namely the product of Movement Disorders Cochane Review Group and the Movement Disorders Society Evidence-Based Review of Parkinson Disease treatments. The concept of management guidelines is presented along with commentaries to the potential variability of recommendations across the world. 3. Limitations of the clinical trials on Parkinson disease treatment so far available.

Evidence-Based Medicine↗
PubMed2002

Sudden death and variant angina.

Variant angina is defined by chest pain occurring at rest associated with transitory ST segment elevation on ECG, and is caused by a spasm of a coronary artery. Frequently, variant angina is associated with atherosclerotic coronary obstruction and patients with normal coronary arteries are rare. Patients with variant angina and normal coronary arteries have good prognosis, and the development of ventricular arrhythmias or sudden death is rare. The authors present two cases of sudden cardiac death in patients with variant angina and normal coronary arteries.

Angina Pectoris, Variant↗
PubMed2002

Cardiac disease outcomes in clinical trials.

Randomized controlled trials (RCTs) are the gold standard for determining causality in medicine. To be considered valid, the efficacy/effectiveness of a new drug must be tested and proved through this type of scientific study. This type of trial will disclose the drug's risk profile as well as the treatment effect magnitude. The proper design, development, and analysis and presentation of results from an RCT is based on a group of well-defined methodological rules, compliance with which assures the trial's internal validity, the relative and absolute importance of the results and its applicability to populations of patients different from those included in the study sample (external validity). Among the structural and methodological components of a clinical trial--randomization, allocation concealment, confounding, similarity of study groups, measures of efficacy, statistical analysis, etc.--disease markers (endpoints, outcomes) are especially important. In the end, what an RCT is good for is to detect changes in the disease process with therapy (or preventive measures), and these changes are defined beforehand based on specific measurements--disease markers. In this paper we will present general principles for the definition of disease markers, their problems and practical use. Caution should be exercised, as this is an area of clinical epidemiology that is somewhat complex, controversial and ill-defined.

Databases, Factual↗