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João Freitas

Publications and source records attributed to João Freitas.

12 recordsLinked to original sources
PubMed2007

The prevalence of genetic and serologic markers in an unselected European population-based cohort of IBD patients.

BACKGROUND AND AIM: The aetiology of inflammatory bowel disease (IBD) is unknown, but it has become evident that genetic factors are involved in disease susceptibility. Studies have suggested a north-south gradient in the incidence of IBD, raising the question whether this difference is caused by genetic heterogeneity. We aimed to investigate the prevalence of polymorphisms in CARD15 and TLR4 and occurrence of anti-Saccharomyces cerevisiae (ASCA) and antineutrophil cytoplasmic antibodies (pANCA) in a European population-based IBD cohort. METHODS: Individuals from the incident cohort were genotyped for three mutations in CARD15 and the Asp299gly mutation in TLR4. Levels of ASCA and pANCA were assessed. Disease location and behaviour at time of diagnosis was obtained from patient files. RESULTS: Overall CARD15 mutation rate was 23.9% for CD and 9.6% for UC patients (P < 0.001). Mutations were less present in the Scandinavian countries (12.1%) versus the rest of Europe (32.8%) (P < 0.001). Overall population attributable risk was 11.2%. TLR4 mutation rate was 7.6% in CD, 6.7% in UC patients and 12.3% in healthy controls (HC), highest among South European CD patients and HC. ASCA was seen in 28.5% of CD patients with no north-south difference, and was associated with complicated disease. pANCA was most common in North European UC patients and not associated with disease phenotype. CONCLUSION: The prevalence of mutations in CARD15 varied across Europe, and was not correlated to the incidence of CD. There was no association between mutations in TLR4 and IBD. The prevalence of ASCA was relatively low; however related to severe CD.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2006

Does pregnancy change the disease course? A study in a European cohort of patients with inflammatory bowel disease.

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) often affects patients in their fertile age. The aim of this study was to describe pregnancy outcome in a European cohort of IBD patients. As data are limited regarding the effect of pregnancy on disease course, our second objective was to investigate whether pregnancy influences disease course and phenotype in IBD patients. METHODS: In a European cohort of IBD patients, a 10-yr follow-up was performed by scrutinizing patient files and approaching the patients with a questionnaire. The cohort comprised 1,125 patients, of whom 543 were women. Data from 173 female ulcerative colitis (UC) and 93 Crohn's disease (CD) patients form the basis for the present study. RESULTS: In all, 580 pregnancies, 403 occurring before and 177 after IBD was diagnosed, were reported. The rate of spontaneous abortion increased after IBD was diagnosed (6.5% vs. 13%, p = 0.005), whereas elective abortion was not significantly different. 48.6% of the patients took medication at the time of conception and 46.9% during pregnancy. The use of cesarean section increased after IBD diagnosis (8.1% vs 28.7% of pregnancies). CD patients pregnant during the disease course, did not differ from patients who were not pregnant during the disease course regarding the development of stenosis (37% vs 52% p = 0.13) and resection rates (mean number of resections 0.52 vs 0.66, p = 0.37). The rate of relapse decreased in the years following pregnancy in both UC (0.34 vs 0.18 flares/yr, p = 0.008) and CD patients (0.76 vs 0.12 flares/yr, p = 0.004). CONCLUSIONS: Pregnancy did not influence disease phenotype or surgery rates, but was associated with a reduced number of flares in the following years.

Adult↗
PubMed2005

Neurohormonal behavior during prolonged orthostatic stress in normotensive subjects.

Prolonged orthostatic stress induces major changes in hemodynamic and autonomic nervous system function. The neurohormonal response to acute and prolonged orthostatic stress that may trigger neurocardiogenic syncope is not clear. The goal of this study was to assess neurohormonal changes during acute and prolonged orthostatic stress. In fifteen normotensive subjects without medication blood was sampled at supine rest (S), during early passive orthostatic stress (after first 10 min.) (T1) and after prolonged (>40 min.) orthostatic stress (T2). We measured atrial and brain natriuretic peptides (ANP and BNP) and catecholamines [norepinephrine (NOR), epinephrine (EPI) and dopamine (DOP)]. ANP was 7.0 +/- 4.3 pmol/l during S, 7.3 +/- 5.1 during T1 and 4.6 +/- 2.8 during T2 (NS and p < 0.05). BNP was 1.9 +/- 1.6 pmol/l during S, 1.7 +/- 1.5 during T1 and 1.4 +/- 1.3 during T2 (p < 0.05 and p < 0.05). NOR was 172 +/- 92 pg/ml during S, 378 +/-_216 during T1 and 402 +/- 183 during T2 (p < 0.01 and NS). EPI was 10.4 +/- 3.8 pg/ml during S, 22.2 +/- 9.3 during T1 and 44.4 +/- 26.0 during T2 (p < 0.01 and p < 0.01). DOP was 7.8 +/- 4.8 pg/ml, 7.6 +/- 2.1 during T1 and 7.0 +/- 2.3 during T2 (NS and NS), Neurohormonal responses to orthostatic stress varied. Natriuretic peptides (ANP and BNP) decreased with prolonged orthostatic stress, probably due to the progressive hypovolemia it induced. Dopamine levels did not change, whereas norepinephrine and epinephrine showed a considerable rise following acute orthostatic stress, with epinephrine rising still further with prolonged orthostatic stress. Neurohormonal responses to prolonged orthostatic stress could help to clarify the pathophysiology of neurocardiogenic syncope.

Acute Disease↗
PubMed2005

Circadian heart rate and blood pressure variability in autonomic failure.

Autonomic failure (AF) induces disabling orthostatic symptoms. Short-term heart rate (HR) and blood pressure (BP) orthostatic patterns are well characterized in these patients but data on long-term blood pressure and heart rate monitoring is lacking. The aim of this study was to assess circadian HR and BP variation in AF patients. We studied 8 patients with severe AF (7 with TTRmet30+ familial amyloidotic polyneuropathy and 1 with pure autonomic fairure)--Group A, and 2 control groups (8 asymptomatic TTRmet30+ patients--Group B, and 16 normal aged-matched controls--Group C). All groups underwent 24h HR and BP monitoring. Twenty-four-hour systolic (SBP) and diastolic BP (DBP) were similar in all groups (114.5+/-10.6 and 73.2+/-6.7; 123.0+/-6.2 and 79.0+/-9.5; 118.6+/-10.1 and 71.4+/-9.4 mmHg for groups A, B and C respectively). BP dipping was attenuated or even inverted (p < 0.01) in AF patients (SBP and DBP differences between day and night: -1.6+/-11.6 and 3.3+/-6.3; 10.0+/-1.0 and 11.7+/-1.5; 15.6+/-7.9 and 16.2+/-5.8 mmHg for groups A, B and C respectively; p < 0.01). Although mean 24h HR was similar between patients and controls (80.9+/-14.0, 87.0+/-4.6 and 80.7+/-5.2 bpm for groups A, B and C respectively), there were striking differences in heart rate variability between groups (max-min 24h HR difference: 46+/-16, 89+/-11 and 91+/-9 bpm; pNN50: 0+/-0, 6+/-2 and 12+/-6%; SDRR 68+/-24, 128+/-10 and 148+/-32 ms for groups A, BB and C; p < 0.01). There were significant differences between normal controls and asymptomatic TTRmet30+ controls in mean HR, diastolic blood pressure dipping and pNN50; p < 0.05. Autonomic failure can be suspected by simple 24h blood pressure evaluation and heart rate monitoring. Asymptomatic TTRmet30+ patients may already show some degree of autonomic impairment, particularly early vagal dysfunction.

Adult↗
PubMed2004

Anti- and pro-oxidant effects of quercetin in copper-induced low density lipoprotein oxidation. Quercetin as an effective antioxidant against pro-oxidant effects of urate.

We recently reported that, depending on its concentration, urate is either a pro- or an antioxidant in Cu(2+)-induced low-density lipoprotein (LDL) oxidation. We also previously demonstrated an antioxidant synergy between urate and some flavonoids in the Cu(2+)-induced oxidation of diluted serum. As a result, the effect of the flavonoid quercetin on the Cu(2+)-induced oxidation of isolated LDL has been studied either in the presence or absence of urate. We demonstrate that, like urate, quercetin alone, at low concentration, exhibits a pro-oxidant activity. The pro-oxidant behavior depends on the Cu(2+) concentration but it is not observed at high Cu(2+) concentration. When compared with urate, the switch between the pro- and the antioxidant activities occurs at much lower quercetin concentrations. As for urate, the pro-oxidant character of quercetin is related to its ability to reduce Cu(2+) with the formation of semioxidized quercetin and Cu(+) with an expected yield larger than that obtained with urate owing to a more favorable redox potential. It is also shown that the pro-oxidant activity of urate can be inhibited by quercetin. An electron transfer between quercetin and semioxidized urate leading to the repair of urate could account for this observation as suggested by recently published pulse radiolysis data. It is anticipated that the interactions between quercetin-Cu(2+)-LDL and urate, which are tightly controlled by their respective concentration, determine the balance between the pro- and antioxidant behaviors. Moreover, as already observed with other antioxidants, it is demonstrated that quercetin alone behaves as a pro-oxidant towards preoxidized LDL.

Alkenes↗
PubMed2004

Carotid sinus syndrome in an unselected population of eight hundred consecutive patients with syncope. Prevalence and clinical profile.

Carotid sinus syndrome (CSS) is frequently underdiagnosed in patients with unexplained syncope or falls. The goal of our study was to assess the value of carotid sinus massage (CSM) in an unselected population with syncope, in the supine position and after prolonged orthostasis. We observed 824 consecutive patients with unexplained syncope referred to our Autonomic Laboratory between October and October 2000 (36 months). For the analysis we studied only patients aged over 42 years (the age of the youngest patient with CSS). One hundred and eight normal healthy subjects served as the control group. CSM was performed after beat-by-beat blood pressure and continuous electrocardiographic monitoring, during supine rest and after prolonged (45 min) orthostasis on a motor-driven tilt table (HTT). Three hundred and eighty-six patients were selected (all more than 42 years old and with unexplained syncope). Six of them were excluded because of contraindication to CSM. Seventy-five patients (20%) had CSS (28% cardioinhibitory type, 22% pure vasodepressor response and 50% mixed type). Forty patients had CSS diagnosed in the supine position and 35 only after HTT. The response type was similar in both positions. The control group had only one positive response after HTT. CSS was more prevalent in males (66/9). We concluded that in an elderly population CSS is a frequent cause of syncope or unexplained falls, particularly in men. CSM in the supine position is 100% specific but only 53% sensitive. Syncope centers should perform CSM with continuous blood pressure monitoring and after prolonged orthostasis.

Adult↗
PubMed2004

Carotid sinus syndrome. Management and approach.

Full description of pathophysiological assessment and definition of carotid sinus hypersensitivity. Detailed focus on clinical and autonomic evaluation. Therapeutic approaches to cardioinhibitory and vasodepressor components are also discussed.

Carotid Artery Diseases↗
PubMed2002

Anti- and pro-oxidant effects of urate in copper-induced low-density lipoprotein oxidation.

We reported earlier that urate may behave as a pro-oxidant in Cu2+-induced oxidation of diluted plasma. Thus, its effect on Cu2+-induced oxidation of isolated low-density lipoprotein (LDL) was investigated by monitoring the formation of malondialdehyde and conjugated dienes and the consumption of urate and carotenoids. We show that urate is antioxidant at high concentration but pro-oxidant at low concentration. Depending on Cu2+ concentration, the switch between the pro- and antioxidant behavior of urate occurs at different urate concentrations. At high Cu2+ concentration, in the presence of urate, superoxide dismutase and ferricytochrome c protect LDL from oxidation but no protection is observed at low Cu2+ concentration. The use of Cu2+ or Cu+ chelators demonstrates that both copper redox states are required. We suggest that two mechanisms occur depending on the Cu2+ concentration. Urate may reduce Cu2+ to Cu+, which in turn contributes to formation. The Cu2+ reduction is likely to produce the urate radical (UH.-). It is proposed that at high Cu2+ concentration, the reaction of UH.- radical with generates products or intermediates, which trigger LDL oxidation. At low Cu2+ concentration, we suggest that the Cu+ ions formed reduce lipid hydroperoxides to alkoxyl radicals, thereby facilitating the peroxidizing chain reaction. It is anticipated that these two mechanisms are the consequence of complex LDL-urate-Cu2+ interactions. It is also shown that urate is pro-oxidant towards slightly preoxidized LDL, whatever its concentration. We reiterate the conclusion that the use of antioxidants may be a two-edged sword.

Animals↗
PubMed2002

Rofecoxib: a possible cause of acute colitis.

Nonsteroidal antiinflammatory agents may cause relevant small bowel and colonic side effects, apart from gastroduodenal lesions. The synthesis of selective cyclooxygenase-2 (COX-2) inhibitors has been an important breakthrough in antiinflammatory therapy by decreasing the incidence of upper gastrointestinal lesions. However, there is little information available concerning their effects on gut mucosa distally to the duodenum. A case history is described of a 52-year-old woman with a temporary colostomy after resection of a sigmoid tumor and who presented with bloody diarrhea 5 days after beginning therapy with rofecoxib. The hemorrhage had its origin in the transverse colon, and the endoscopic appearance was that of actively bleeding acute hemorrhagic colitis. No other colonic lesions were detected, nor was there any evidence of related infection, bleeding diathesis, or other systemic diseases. On discontinuing rofecoxib and instituting parenteral rehydration, the bleeding and diarrhea stopped. Endoscopic follow-up revealed regenerating mucosa in the transverse colon. The time relation, the absence of other causes of hemorrhage, and the clinical evolution all strongly support the probability of a causal relation between rofecoxib and hemorrhagic colitis. This case may raise awareness concerning the possibility of colonic lesions related to the new COX-2 inhibitors, similar to what is known about nonselective antiinflammatory agents.

Acute Disease↗
PubMed2002

B-type natriuretic peptide is related to left ventricular mass in hypertensive patients but not in athletes.

A positive correlation has been previously documented between B-type natriuretic peptide (BNP) levels and left ventricular mass index (LVMI) in hypertensive patients. We evaluated 8 cycling athletes, 8 healthy age-matched controls; 17 hypertensive patients and 7 age-matched controls. LVMI was significantly higher in athletes and hypertensive patients than in their controls. Plasma levels of BNP in hypertensive patients were significantly higher than in athletes and their age-matched controls. No significant difference was found between athletes and their controls. Cycling athletes had significantly larger LVMI than hypertensive patients and controls, without elevated BNP levels. These results suggest that BNP levels are elevated in patients with increased LVM due to hypertension but not in physiologically increased LVM. Whether elevated BNP levels in athletes is a sign of structural heart disease merits further investigation.

Adult↗