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Biomedical subjects

J Freitas

Publications and source records attributed to J Freitas.

At least 19 recordsLinked to original sources

Hemodynamic, autonomic and neurohormonal behaviour of familial amyloidotic polyneuropathy and neurally mediated syncope patients during supine and orthostatic stress.

Orthostatic intolerance (OI) syndromes are frequent and share symptoms like dizziness and orthostatic syncope. Their pathophysiology however seems to be different. The aim of our work was to evaluate autonomic and hemodynamic behaviour in patients with familial amyloidotic polyneuropathy and neurally mediated syncope in supine position and after acute orthostatic passive stress. We studied 12 patients with autonomic failure (group A), 12 patients with neurally mediated syncope (group B) and 16 aged matched normal controls (group C), in supine position and during the first 10 min of head-up tilt test (HUTT). Beat-by-beat blood pressure and heart rate were continuously monitored and digitised at 500 Hz. The baroreceptor alfa-index gain (vagal reflex-BRG), high frequency of RR variability (HFRR, vagal tonus) and low frequency of systolic arterial pressure variability (LFSAP, sympathetic tone) were calculated. Catecholamines, plasma brain (BNP) and atrial natriuretic (ANP) peptides were also measured. Hemodynamic data were derived and calculated by the non-invasive modelflow method. During supine position, cardiac output (CO) and stroke volume (SV) were similar in all groups. Mean arterial pressure (MAP) and BNP were higher in group A. Noradrenaline (NOR), BRG, HFRR and LFSAP were extremely low in this group. BRG and adrenaline (ADR) were higher in group B than in controls. Within the first 10 min of HUTT, there was a huge drop of CO, SV and MAP in group A, maintenance of very low levels of neurohormones and lack of autonomic function. HR, LFSAP and ADR had a higher rise at HUTT in group B compared with controls (p<0.01) but a significant decrease of BRG was noted (p<0.05). ANP or BNP did not change with tilt in any group. Different orthostatic intolerance syndromes may show important hormonal, autonomic and hemodynamic differences during supine rest and enhanced after passive orthostatism.

Adult↗

Phenotype at diagnosis predicts recurrence rates in Crohn's disease.

BACKGROUND: In Crohn's disease (CD), studies associating phenotype at diagnosis and subsequent disease activity are important for patient counselling and health care planning. AIMS: To calculate disease recurrence rates and to correlate these with phenotypic traits at diagnosis. METHODS: A prospectively assembled uniformly diagnosed European population based inception cohort of CD patients was classified according to the Vienna classification for disease phenotype at diagnosis. Surgical and non-surgical recurrence rates throughout a 10 year follow up period were calculated. Multivariate analysis was performed to classify risk factors present at diagnosis for recurrent disease. RESULTS: A total of 358 were classified for phenotype at diagnosis, of whom 262 (73.2%) had a first recurrence and 113 patients (31.6%) a first surgical recurrence during the first 10 years after diagnosis. Patients with upper gastrointestinal disease at diagnosis had an excess risk of recurrence (hazard ratio 1.54 (95% confidence interval (CI) 1.13-2.10)) whereas age >/=40 years at diagnosis was protective (hazard ratio 0.82 (95% CI 0.70-0.97)). Colonic disease was a protective characteristic for resective surgery (hazard ratio 0.38 (95% CI 0.21-0.69)). More frequent resective surgical recurrences were reported from Copenhagen (hazard ratio 3.23 (95% CI 1.32-7.89)). CONCLUSIONS: A mild course of disease in terms of disease recurrence was observed in this European cohort. Phenotype at diagnosis had predictive value for disease recurrence with upper gastrointestinal disease being the most important positive predictor. A phenotypic North-South gradient in CD may be present, illustrated by higher surgery risks in some of the Northern European centres.

Adult↗

Temporal arteritis presenting with scalp ulceration.

We report the case of a 75-year-old-woman who presented with bilateral scalp ulcerations and blindness, accompanied by severe headache and scalp tenderness, due to bilateral temporal arteritis without systemic involvement. A biopsy taken from the border of an ulceration showed evidence of giant cell arteritis. She was treated with oral prednisone, 60 mg per day. The ulcerations healed in a few weeks but the vision loss was irreversible. This case highlights for temporal arteritis the importance of accurate and timely diagnosis as well as the need for prompt therapy with systemic steroids in order to avoid major complications, namely loss of vision. It also demonstrates that scalp necrosis and ulcerations are skin signs associated with a poor prognosis.

Aged↗

[Mycobacterium avium complex in water buffaloes slaughtered for consumption].

Two mycobacterium strains isolated from lung tissue a apical lymph nodes of slaughtered water buffaloes were biochemically analyzed and identified as Mycobacterium avium complex strains. Association between these microorganisms and the acquired immunodeficiency syndrome, and the potential risk posed by eating infected animals and their products, was discussed.

Animals↗

Clinical improvement in patients with orthostatic intolerance after treatment with bisoprolol and fludrocortisone.

Orthostatic intolerance is the development of disabling symptoms upon assuming an upright posture that are relieved partially by resuming the supine position. Postural tachycardia syndrome (POTS) is an orthostatic intolerance syndrome characterized by palpitations because of excessive orthostatic sinus tachycardia, lightheadedness, tremor, and near-syncope. Patients usually undergo extensive medical, cardiac, endocrine, neurologic, and psychiatric evaluation, which usually fails to identify a specific abnormality. The authors investigated the autonomic and hemodynamic profile of patients with POTS and the effectiveness of bisoprolol and fludrocortisone. The authors evaluated 11 female patients with POTS before and after medical treatment with a cardioselective bisoprolol beta-blocker or fludrocortisone, or both, and 11 age-matched control patients. Variability of heart rate and systolic blood pressure was assessed by fast Fourier transform, and spontaneous baroreceptor gain was assessed by use of the temporal sequences slope and alpha index. Modelflow was used to quantify hemodynamics. Symptoms in all patients improved greatly after medication. The autonomic and hemodynamic impairment observed in patients with POTS, particularly after orthostatic stress, is treated effectively with bisoprolol or fludrocortisone or both. These results need further confirmation in a controlled double-blind study. Proper medical treatment improves dramatically the clinical and autonomic-hemodynamic disturbances observed in patients with POTS. The data support the hypothesis that POTS is the result of a hyperadrenergic activation or hypovolemia during orthostasis.

Adolescent↗

Clastogenic factors as biomarkers of oxidative stress in chronic hepatitis C.

BACKGROUND/AIMS: Clastogenic factors (CFs) are composed of lipid peroxidation products, cytokines and other oxidants with chromosome-damaging properties. They are regularly observed after radiation exposure and in chronic inflammatory diseases, where they are supposed to be risk factors for carcinogenesis. It appeared of interest to investigate their presence in the plasma of patients with chronic hepatitis C. METHODS: CFs are detected by chromosomal breakage studies. They were compared to malondialdehyde (MDA), total plasma thiols (t-SH), alanine aminotransferase (ALT), viral load and histological data. RESULTS: CFs were increased in 19 of 20 patients, 16 had increased MDA levels and 15 had decreased t-SH levels. Mean values were significantly different from the 20 controls (p<0.001). After the first 3 months of interferon treatment, all three markers showed significant improvement, but were not completely normalized. There was a positive correlation between CFs and necroinflammatory activity (p<0.03), while MDA was correlated with fibrosis (p<0.03). Viral load was correlated with necrosis and inflammation (p<0.05). CONCLUSION: The presence of CFs in chronic hepatitis C confirms the occurrence of oxidative stress in this disease and could be useful in clinical trials for testing antioxidants. The CF test is a sensitive assay for the detection of oxidative stress and correlates with necroinflammatory activity.

Adult↗

Diurnal blood pressure variation in progressive autonomic failure.

To investigate the role of the autonomic nervous system (ANS) in the generation of the circadian blood pressure (BP) variation, the degree of impairment of the ANS was related to the results of ambulatory BP recordings in 212 patients with progressive autonomic failure due to familial amyloid polyneuropathy. On the basis of BP and/or heart rate (HR) responses to the Valsalva maneuver, 60 degrees head-up tilting, deep-breathing tests, and plasma norepinephrine levels, 4 groups of patients were distinguished. In all patients and in 38 age-matched control subjects, ambulatory BP was monitored. Patients of group I (n=40, aged 32+/-3 y), with no evidence yet of impairment of their ANS, had circadian BP and HR variations indistinguishable from controls. Patients of group II (n=41, aged 34+/-5 y) had a variable degree of impairment of their parasympathetic ANS, but their sympathetic ANS was still intact. Twenty-four-hour HR was higher in these patients than in controls (88+/-11 versus 78+/-7 bpm, P<0.01). Their circadian HR variation was maintained, but their circadian BP variation was diminished (10+/-6/11+/-4 versus 17+/-6/16+/-4 mm Hg in controls, P<0.01) because of an attenuation of the nocturnal BP decline. Patients of group III (n=69, aged 36+/-6 y), with parasympathetic failure and intermediate sympathetic dysfunction, had a blunted diurnal BP variation, whereas patients of group IV (n=62, aged 38+/-6 y), with parasympathetic failure and severe sympathetic dysfunction, had an absent diurnal BP variation. In patients of groups III and IV, a decrease in daytime BP accounted for the blunted circadian BP variation. This extensive study in progressive autonomic failure confirms the important role of the ANS in the generation of circadian BP variation. For the maintenance of a normal circadian BP pattern, not only an intact sympathetic but also an intact afferent parasympathetic ANS is a prerequisite.

Adult↗

Reversible sympathetic vasomotor dysfunction in POTS patients.

BACKGROUND: Orthostatic intolerance refers to the development upon assuming an upright posture of disabling symptoms, which are partly relieved by resuming the supine position. Postural tachycardia syndrome (POTS) is an orthostatic intolerance syndrome characterized by palpitations due to excessive orthostatic sinus tachycardia, lightheadedness, tremor, and near-syncope. Patients usually undergo extensive medical, cardiac, endocrine, neurological and psychiatric evaluation, which usually fails to identify a specific abnormality. We investigated the autonomic and hemodynamic profile of POTS patients and the efficacy of bisoprolol and or fludrocortisone. METHODS AND RESULTS: We evaluated eleven female patients with POTS before and after medical treatment with a cardio-selective beta blocker (bisoprolol) and/or fludrocortisone, and eleven age-matched controls. Variability of heart rate and systolic blood pressure was assessed by Fast Fourier Transform, and spontaneous baroreceptor gain by temporal sequences slope and alpha index. Modelflow was used to quantify hemodynamics. All patients improved greatly after medication. The autonomic and hemodynamic impairment observed in patients with POTS, particularly after orthostatic stress, is treated effectively with bisoprolol and/or fludrocortisone. These results need further confirmation in a controlled double-blind study. CONCLUSIONS: Proper medical treatment dramatically improves the clinical and autonomic/hemodynamic disturbances observed in patients with POTS. The data support the hypothesis that POTS is due to a hyperadrenergic activation and/or hypovolemia during orthostasis.

Adolescent↗

Role of autonomic nervous system and hemodynamics in cardiovascular homeostasis after orthostatic stress.

Autonomic control of hemodynamics is crucial to maintaining cardiovascular homeostasis after orthostasis. Our goal was to assess the effect of passive orthostatic stress on cardiovascular hemodynamics regulation by analysis of the autonomic nervous system (ANS) and gender influence on the variables. We used a passive 70 degrees tilt test as an orthostatic maneuver. For SNA measurements we used FFT for HRV and SBPV, temporal sequences and alpha index to calculate baroreceptor gain. Hemodynamic data was calculated non-invasively by modelflow. Orthostatic stress induces a rise in heart rate (+15%), total peripheral resistance (+28%), sympathetic tonus (LF_nu: +32%; LF_pas: +64%) and a reduction in cardiac output (-28%), systolic volume (-43%), and vagal activity both tonic (HF_nu:-115%) and reflex (BRG:-103%). Females had higher vagal activity regardless of position. We concluded that the autonomic nervous system plays a crucial role in cardiovascular hemodynamics control to maintain homeostasis after orthostatic stress.

Adult↗

Impaired arterial baroreceptor sensitivity before tilt-induced syncope.

Autonomic dysfunction seems to play a central role in the pathophysiology of neurocardiogenic syncope (NCS) but conflicting data have recently become available. We evaluated autonomic nervous system (ANS) function (heart rate variability (HRV), systolic blood pressure variability (SBPV) and baroreceptor gain (BRG)) and non-invasive haemodynamics (cardiac output and total peripheral resistance) in patients with neurocardiogenic syncope. Retrospectively, we evaluated 12 NCS patients (positive head-up tilt without pharmacological provocation) in the basal state and at initial tilt, 12 non-NCS patients with tilt-negative syncope and 12 aged-matched normal controls. Prospectively, we evaluated 16 NCS patients to analyse the haemodynamics and ANS activity throughout the tilt test (beginning of tilt and before syncope occurs). HRV and SBPV were accessed by fast Fourier transforms (FFT) and spontaneous BRG by temporal sequences, slope and a index. Modelflow was used to quantify the non-invasive haemodynamics. None of the autonomic and haemodynamic parameters at baseline or in the first 10 min of tilt was different among the respective NCS, non-NCS syncope and normal control groups, except for SBP, which was higher at baseline in controls. Throughout the tilt test in the prospective NCS group, the heart rate increased (88-95 beats x min(-1), P<0.05), systolic blood pressure decreased (123-109 mmHg, P<0.01), and arterial baroreceptor gain was reduced (7.6 to 5.5 ms mmHg(-1), P<0.01) and the absolute high frequency component of HRV (HF HRV) decreased (150-80 ms(-2), P<0.05), before syncope occurred. There was no change in the low frequency component of HRV (LF HRV), SBPV, cardiac output (CO) or total peripheral resistance (TPR). Tilt-induced syncope could not be predicted by non-invasive haemodynamic or autonomic parameters at rest or in the initial minutes of tilt. The decrease in arterial baroreceptor gain could be a precocious expression of the transient autonomic dysfunction that characterizes the occurrence of neurocardiogenic syncope.

Adult↗

Role of sympathetic nervous system in cyclosporine-induced rise in blood pressure.

To clarify the role of the sympathetic nervous system in the development of cyclosporine A (CsA)-induced rise in blood pressure (BP), the effects of CsA on 24-hour ambulatory BP (ABP) were studied in patients with familial amyloid polyneuropathy (FAP) who underwent a liver transplantation. On the basis of autonomic function tests, patients with absent or mild-to-moderate sympathetic damage (Group A, n=11, age 29 to 43 years, disease duration 2 to 6 years) and patients with severe sympathetic damage (Group B, n=9, age 27 to 38 years, disease duration 3 to 9 years) were identified. Both groups were followed for 1 year. The daily doses of CsA and the CsA whole blood trough levels between the groups did not differ. Pretransplantation values of daytime and nighttime ABP were, respectively, 117+/-8/76+/-7 mm Hg and 108+/-12/68+/-9 mm Hg in group A and 107+/-6/66+/-4 mm Hg (P<0.05 group A versus group B) and 102+/-6/62+/-4 mm Hg in group B. In response to CsA, BP increased in all patients, but more so in patients of group B than in patients of group A. One year after transplantation, daytime and nighttime ABP had increased by 6+/-9/3+/-11% and 12+/-10/14+/-14% in group A and by 12+/-6/13+/-10% (P<0.05) and 21+/-11/27+/-21% (P<0.01) in group B. In both groups, the increase in nighttime ABP was greater than the increase in daytime ABP, which resulted in an attenuation or, even, a reversal of the diurnal BP rhythm. Because the rise in BP was greater in patients with more advanced sympathetic dysfunction, the sympathetic nervous system appears to counteract the CsA-induced rise in BP rather than causing it. This implies involvement of factors other than sympathetic activation in the pathogenesis of CsA-induced rise in BP in patients with familial amyloid polyneuropathy.

Adult↗

Cellular penetration of fluorescently labeled superoxide dismutases of various origins.

BACKGROUND: Using fluorescently labeled superoxide dismutase (SOD) and flow cytometry, we have shown previously that the enzyme CuZn SOD (EC 1.15.1.1) from bovine erythrocytes binds rapidly to the cell surface with slow uptake into the cell during the following hours. The degree of labeling was most important for monocytes in comparison to other blood cells (erythrocytes, lymphocytes, and neutrophils) and fibroblasts. In agreement with the flow-cytometric findings, the inhibition of superoxide production was more important for SOD-pretreated monocytes than for neutrophils, as demonstrated with the cytochrome c reduction assay. It was thus of interest to confirm the observed differences between monocytes and neutrophils with confocal laser microscopy, study in greater detail the kinetics of binding, penetration, and intracellular localization of the enzyme, and compare the results obtained with bovine CuZn SOD with those from SODs of other origins and carrying different active sites. MATERIALS AND METHODS: Recombinant human (rh), bovine, and equine CuZn SODs, as well as rh and E. coli Mn SODs, were studied before use with respect to specific activity and purity (HPLC, SDS-PAGE electrophoresis). Fluorescein isothiocyanate was covalently conjugated to the various SODs for study with high-resolution confocal scanning laser microscopy. Superoxide production by monocytes and neutrophils was measured with the cytochrome c assay. RESULTS: As expected from our experiments with flow cytometry, only rare neutrophils were labeled with FITC-SOD, even with the longest incubation time of 3 hr and the highest dose of 1500 units/ml. In addition, they showed a localized fluorescence pattern that was quite different from the diffuse punctate fluorescence pattern of monocytes. Lymphocytes were not labeled at all. The rapid binding to the cellular surface of monocytes was confirmed, and even after 5 min of preincubation, FITC-SOD was found on a small percentage of monocytes. This was correlated with a reduction in superoxide release after phorbolmyristate acetate (PMA) stimulation by 40%. An interesting finding was the perinuclear accumulation of the penetrated SOD after the longest pretreatment of 3 hr, suggesting a barrier against further progression. Indeed, through confocal microscopy we were able to exclude any fluorescence at the nuclear level. While the fluorescence labeling patterns and the kinetics of penetration were quite similar for bovine, equine, and rh CuZn SOD, the Mn SODs showed poor labeling, correlated with a weak inhibitory effect on cytochrome c reduction, which was not statistically significant. CONCLUSIONS: The rapid binding of native CuZn SODs on the surface of monocytes, leading to reduced superoxide release by these cells, explains the observation that beneficial effects of injected SOD lasted for months despite rapid clearance of the enzyme from the bloodstream, according to pharmacodynamic studies. The preferential binding to monocytes, in contrast to neutrophils, may play a role in chronic inflammatory diseases in which the monocytes are in an activated state. The differences in binding capacity between CuZn SODs and Mn SODs, correlated with different inhibitory effects of superoxide production by monocytes, may also have therapeutic significance.

Animals↗

Acute colitis caused by caustic products.

We report two cases of acute proctocolitis caused by rectal application of caustic products of domestic use. One 61-yr-old woman applied an ammonia solution enema; the other patient, a 63-yr-old woman, accidentally applied an enema containing lye. Both patients presented with intense anal pain, but the first patient also had abdominal pain with guarding, hematochezia, and leucocytosis. An acute proctocolitis was found at sigmoidoscopy in both patients. Only conservative and symptomatic measures were prescribed in both cases, and a clinical and endoscopic recovery was seen. In spite of persistent fibrosis in the lamina propria, no signs of stenosis were found.

Accidents, Home↗