[New parameter for explaining the "natural protection" of the female sex in cardiovascular risk (the value of arterial baroreceptors)].
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Biomedical subjects
Publications and source records attributed to J Freitas.
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Sudden death during sports activities is extremely rare in athletes and sportsmen. Its occurrence was calculated at 0.77 to 13 deaths per 100,000 sportsmen/year. The most frequent causes were coronary heart disease, coronary muscular bridges, congenital coronary artery anomalies, subarachnoid hemorrhage, hypertrophic cardiomyopathy, arrhythmogenic right ventricular dysplasia, Marfan syndrome, aortic coarctation, myocarditis, pulmonary embolism, aortic stenosis, mitral valve prolapse and WPW syndrome. Clinical examination nearly identifies all cases of aortic stenosis, mitral valve prolapse with regurgitation, and aortic coarctation but misses the majority of cases of hypertrophic cardiomyopathy and coronary artery diseases. The use of Chest x-rays, ECG, Stress Test and Echocardiogram will provide the identification of most cases with increased risk of death. Although costs are not limited for professional athletes, this strategy does not totally overcome the problem because diagnostic errors are frequent (false positives and false negatives). Therefore it is important to admit the failure of these screening procedures and the necessity to adapt the strategy to cost-efficiency and time-efficiency in this population.
An overview is made of the orthostatic intolerance syndromes and a clinical case of postural tachycardia syndrome.
Disabling orthostatic hypotension, due to insufficiency of the autonomic nervous system, is a common complication of type I familial amyloidotic polyneuropathy (FAP). We investigated whether oral treatment with L-threo-3,4-dihydroxyphenylserine (L-threo-Dops), a noradrenaline precursor, might be of therapeutical benefit. In twenty untreated FAP patients, aged 33 to 44 years, who, because of severe orthostatic hypotension, were bedridden or constrained to a sitting life, supine and erect blood pressure (BP), plasma noradrenaline and tilting time, defined as the interval (s) between the beginning of a 60 degrees head-up tilt and the occurrence of orthostatic symptoms (dizziness, blurred vision or near syncope) were determined before and at repeated intervals during oral treatment with L-threo-Dops, 100 mg bid, for 6 months. Before treatment supine mean BP was 80 (76-85) mmHg (mean and 95% CI), supine plasma noradrenaline was low, 59 (41-77) pg/ml and tilting time ranged from 38 to 118 s. In response to tilt, mean BP immediately fell by 36 (31-41) mmHg, whereas plasma noradrenaline increased by only 11 (0-21) pg/ml (p = 0.05). After 3 to 5 days of treatment with L-threo-Dops all patients experienced marked improvement of their orthostatic tolerance as reflected by their ability to walk freely around. This effect sustained throughout the six months of treatment. Plasma noradrenaline increased moderately by 37 (11-63) pg/ml (p = 0.02) and supine mean BP increased by 8.6 (5.8-12.4) mmHg (p < 0.001) during chronic treatment. Supine or nocturnal hypertension did not develop, the fall in mean BP in response to tilt diminished by 12.5 (6.5-17.3) mmHg (p < 0.001) and tilting time became longer than 600 s in all patients. Because of its efficacy, its sustained duration of action and the lack of side effects, L-threo-Dops is advocated to improve orthostatic tolerance in patients with autonomic insufficiency due to FAP.
The objective of this study was to assess the influence of day-night cycle and sleep-awake period on the circadian pattern of heart rate variability (HRV). Twelve male oil refinery security shift workers, aged 39 +/- 7 years, were studied with 24-hour Holter monitor recordings during morning and night work periods. Hourly HRV parameters in the time and frequency domains were evaluated. For both shifts, all HRV parameters during awake or work periods were found not to be statistically different. In both day and night work shifts, the very low frequency and high-frequency components of HRV and the proportion of differences in successive R-R intervals greater than 50 ms increased during the sleep period, while the low frequency/high frequency ratio decreased. The low-frequency component in absolute units and the SD of the R-R interval did not show any variation in either shifts for the different periods. These results suggest that the circadian pattern of HRV seems to be predominantly related to sleep (supine) and wakefulness (standing) and remains independent of night-day cycle.
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Data from the literature, as well as our previous work, indicate a protective effect of superoxide dismutase (SOD) in topical application against UV-induced cutaneous damage. In the present article we show that pre-treatment of the skin with SOD protects against PUVA-induced inflammatory reactions not only in murine, but also in human skin. Using fluorescently labelled Cu,Zn SOD, epifluorescence microscopy and digital image processing, we demonstrate that the FITC fluorescence localizes in the stratum corneum and upper granulosa, as well as in the epidermal cell layer surrounding the lumina of the hair follicles. These findings were similar for murine and human skin. Since autofluorescence was eliminated by a special filter, it can be ascertained that the fluorescence observed in the tissues was due to FITC-labelled SOD.
Psoriasis is a common skin disorder characterized by hyperproliferation and incomplete differentiation of epidermal keratinocytes. Psoralen plus UVA (PUVA) is one of the treatments proposed for this disease. We had reported previously that exposure of regular blood cultures from healthy donors to PUVA leads to chromosomal breakage via the formation of transferable clastogenic materials, a phenomenon inhibitable by superoxide dismutase. In the present paper we show that these clastogenic factors (CF) are also formed in vivo. The CF were found in about 50% of the psoriasis patients studied (14 out of 31). In PUVA-treated psoriasis patients, the clastogenic activity of the plasma increased significantly between the first and the last (16th) exposure to PUVA. We hypothesize that CF formation in psoriasis is similar to that in other diseases accompanied by oxidative stress, in particular chronic inflammatory diseases with autoimmune reactions such as lupus erythematosus, progressive systemic sclerosis, rheumatoid arthritis and others. Increased superoxide production by phagocytes, formation of lipid peroxidation products and release of cytokines are considered to be responsible for the superoxide-stimulating and chromosome-damaging properties of patients' plasma. During PUVA therapy, superoxide generated via the interaction of psoralen with UVA may contribute to CF formation in addition to superoxide from inflammatory cells. An increased risk of cancer and leukemia is observed in diseases accompanied by CF formation. Therefore CF may contribute to the well-known risk of photocarcinogenesis by PUVA therapy. This additional risk may be preventable by antioxidants and superoxide scavengers.
BACKGROUND: Scleroderma patients exhibit increased chromosomal instability due to circulating clastogenic plasma factors (CF). Formation and action mechanisms of CF are mediated by superoxide. In addition, previous work detected inosine triphosphate (ITP) in the plasma of 2 patients, and the enzyme adenosine deaminase (ADA) was found to be increased. OBJECTIVE: To study correlations between CF, ITP and ADA levels, CF and disease activity, as well as other biomarkers of oxidative stress. METHODS: Clastogenic activity was evaluated by means of cytogenetic methods in 48 patients and 55 healthy subjects. ITP was detected by mass spectrometry and electrospray ionisation. ADA was measured with a colorimetric assay and malondialdehyde using the Yagi method. RESULTS: Clastogenic activity was significantly increased in patients' plasma compared to controls. In 10 patients CF, ITP and ADA were studied simultaneously. All three parameters were increased in the 7 patients of subgroups 2 (skin and esophagus involvement) and 3 (skin plus multiple organ involvement). ITP was not detected in 2 patients of subgroup 1 (skin involvement only) with low ADA and CF values. CONCLUSION: ITP, the deamination product of ATP, is one of the clastogenic and superoxide generating components of CF. The formation of this deamination product of ATP is probably related to the increase in ADA. CF are biomarkers of oxidative stress and can be used for evaluation of antioxidant treatments in scleroderma.
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Superoxide-mediated clastogenesis is characteristic for various chronic inflammatory diseases with autoimmune reactions and probably plays a role in radiation-induced clastogenesis and in the congenital breakage syndromes. It is consistently prevented by exogenous superoxide dismutase (SOD), but not by heat-inactivated SOD, indicating that the anticlastogenic effect is related to the catalytic function of the enzyme. Increased superoxide production by activated monocytes/macrophages is followed by release of more long-lived metabolites, so-called clastogenic factors, which contain lipid peroxidation products, unusual nucleotides of inosine, and cytokines such as tumor necrosis factor alpha. Since these components are not only clastogenic, but can stimulate further superoxide production by monocytes and neutrophils, the genotoxic effects are self-sustaining. It is shown here that anticlastogenic effects of exogenous SOD are preserved despite extensive washing of the cells and removal of all extracellular SOD. Using flow cytometry and confocal laser microscopy, rapid adherence of the fluorescently labeled enzyme to the cell surface could be observed with slow uptake into the cell during the following hours. The degree of labeling was concentration and time dependent. It was most important for monocytes, compared with lymphocytes, neutrophils, and fibroblasts. The cytochrome c assay showed significantly diminished O2- production by monocytes, pretreated with SOD and washed thereafter. The preferential and rapid binding of SOD to monocytes may be of importance not only for the superoxide-mediated genotoxic effects, described above, but also from a therapeutic standpoint. It can explain the observation that beneficial effects of injected SOD lasted for weeks and months despite rapid clearance of the enzyme from the blood stream according to pharmacodynamic studies.
This report presents a well-documented link between vasodepressor syncope, a marked increase of LF/HF ratio response to orthostasis (sympathetic dominance), and the efficacy of beta blockers in preventing orthostatic symptoms and absence of tilt-induced syncope, with normalization of the LF/HF ratio response.
The sensitivity and specificity of heart rate variability (HRV) in the corroboration of brain death diagnosis in patients with acute traumatic intracranial lesions was evaluated in 20 patients with clinical criteria of brain death, nine patients in deep coma (Glasgow scale < 7) and 18 normal controls, all age matched. The electrocardiogram was sampled at 650 Hz and several parameters of HRV were calculated, in both time and frequency domains. The HRV parameters were significantly lower in the brain death group compared with the deep coma group. Linear discriminant analysis between brain death and deep coma patients was performed on a data set made of nine randomly selected patients with clinical criteria of brain death and nine patients in deep coma. Cross-validation was performed on the remaining 11 patients with clinical criteria of brain death. All patients in the data set were correctly classified (sensitivity and specificity of 100%). All patients in the cross-validation set were correctly classified (sensitivity of 100%). Further studies are necessary to evaluate the specificity of the method in the independent set of deep coma patients and in the follow-up of comatose and vegetative patients to identify irreversibility of HRV. Nevertheless, these results suggest that HRV analysis constitutes a fully sensitive and specific method for assessing brain death in potential organ donors with acute traumatic lesions of the brain. This fast, quantitative and bedside method seems very promising for the early confirmation of brain death, which is an important factor for the success of transplantation procedures and could have a high predictive value of brain death in comatose patients with brain injuries without fully diagnostic criteria.
Neurocardiogenic syncope seems to be the most common cause of syncope. It is believed to be triggered by paradoxical autonomic reflexes, beginning in the ventricular mechanoreceptors of the heart, modulated by the brain stem and terminating in the autonomic efferent pathways (parasympathetic stimulation with bradycardia or asystole and sympathetic inhibition with severe hypotension). Tilt test has been used recently, as a safety and effective tool to identify subjects prone to syncope. Although the pathophysiology of this syndrome is not completely understood, pharmacological therapeutics seems very effective in resolving symptoms.
Arterial baroreceptors are sensitive to variation in both blood and pulse pressure. When there is an increase in those pressures, the baroreceptors increase the rhythm in which electric impulses are discharged. The impulses are transmitted by the receptors to the nervous centres of the brainstem. Once processed, these signals turn into sympathetic and vagal impulses. The vagal efferents control heart rate and the sympathetic efferents control heart rate, myocardial contractility and peripheral resistance. If there is an increase in blood pressure, then there will be a reflex decrease in the sympathetic activity and an increase in the parasympathetic one. The cardiac cronotropic response to blood pressure variation is very fast-with a delay of one or two beats. The amplitude of the response is a sigmoidal function. The greatest inclination of the response curve, that is to say, the area of greatest variation of the RR interval per unit of pressure, characterises the gain of the baroreceptors. The traditional method for obtaining the gain of the baroreceptor is a pharmacological one. Generally, the patient is given phenilephrine intravenously, in bolus and then the correlation between heart rate and the increase in intra-arterial blood pressure (reflex bradycardia) is calculated. Lately, it has been used the calculation of the spontaneous gain of the baroreceptor starting from a study carried out on the normal fluctuations in blood pressure and in the pulse interval both in time and frequency domain. The first case deals with the calculation of the gain of the function of transfer between the variations both in blood pressure and the RR intervals in the LF and the HF bands. The second case deals with the analysis of the occurrence of sequences of three beats with successive increases or decreases in blood pressure and in the RR interval. The gain is obtained from the linear regression of all the sequences. The application of these techniques to the recordings of blood pressure obtained by non-invasive methods (Finapress) makes possible that this procedure be followed under real conditions since it requires no previous stimulation of the cardiovascular system, which would probably interfere with the mechanisms to be evaluated, and requires no equipment in the condition which is normally required by experimental methodology.
PURPOSE: To analyse the experience with the use of Sideris' device for percutaneous transvenous occlusion of atrial septal defect (ASD). METHODS: Thirty six procedures of ASD occlusion were performed in 32 patients; 27 (84.4%) female and five (15.6%) male, mean age of 16 years (4-61). All patients had secundum atrial septal defects with clinical and hemodynamic compromise. The ASD diameter measured < 31 mm and occupied less than 50% of the septal length in all cases. The basic device was used in 28 (87.5%) patients and the self centered model in four (12.5%). The direct implant technique was employed in 15 (41.7%) procedures while in the other 21 (58.3%) an over a wire technique was used. The size of the device was selected according with the Sideris' normogram. RESULTS: Occlusion of the defect was achieved in 29 patients (90.63%). In two (6.25%) the position of the device was not adequate and in one (3.12%) the device embolized to the pulmonary artery. In these three cases the device was removed surgically during the defect closure. There was neither morbidity nor mortality in this series. Trivial or small residual shunt was detected with color flow mapping in three (9.4%) patients immediately after the procedure. In 22 patients with 12 months follow-up, trivial residual shunt was present in only one (4.5%). Structural modification of the device was detected in one patient, however with complete ASD occlusion and neither clinical nor hemodynamic disturbance. CONCLUSION: The Sideris' device is safe and efficient for ASD occlusion in selected patients. Although there is a relatively high incidence of residual shunt immediately after the procedure, the shunt itself tends to become smaller or disappear during the follow-up and it does not preclude clinical and hemodynamic improvement.
The aim of the present study was to confirm the increase of adenosine deaminase (ADA) activity in progressive systemic sclerosis (PSS), described by Sasaki & Nakajima, and to compare plasma ADA activity of patients in different stages of the disease. Enzyme activity was measured with a colorimetric assay. The 48 patients were subdivided into 3 groups: subgroup 1 (n = 10), disease still limited to the skin; subgroup 2 (n = 21), involvement of the skin and oesophagus; and subgroup 3 (n= 17), involvement of the skin and multiple internal organs. ADA levels were highest in subgroup 3. However, the difference with respect to subgroup 2 did not reach statistical significance. Subgroup 1 was different from controls and subgroups 2 and 3 (p<0.001). Our results confirm that ADA activity is increased in PSS, and that this finding is observed even in the early stages of the disease process. We speculate that the increase in ADA, a well-known marker of T-cell activation, might be an indicator of disease activity in PSS, in the beginning as well as during phases of exacerbation in later stages of the disease.