Atrial natriuretic peptide and brain natriuretic peptide release in human essential hypertension.

Hypertension is associated with an increase in vasoactive peptides, but conflicting results are reported concerning their causes of elevation. In this study, cardiac vasodilator hormones atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), and vasoconstrictor hormones (renin, aldosterone, cortisol, metanephrins) were determined in 36 hypertensive subjects (HT) without left ventricular hypertrophy (LVH), 19 healthy subjects without family hypertension (NTFN) and 35 healthy subjects with family hypertension (NTFH). Plasma levels of ANP and BNP were significantly higher (p<0.04) in HT subjects (28.1 +/- 6.1 and 22.7 +/- 6.8 pg/ml) compared to NTFN (13.4 +/- 3.3 and 6.1 +/- 1.5 pg/ml) and NTFH (12.5 +/- 1.4 and 7.2 +/- 1.3 pg/ml) subjects, respectively. No significant differences were observed in ANP and BNP concentrations between NTFN and NTFH. Measurement of vasoconstrictor hormones showed no significant differences between the three groups. Plasma ANP and BNP concentrations were significantly correlated in both HT (r=0.73; P<0.001), NTFN (r=0.71; P<0.002) and NTFH (r=0.53; P<0.003) subjects. ANP values were significantly related to systolic blood pressure (r=0.34; P<0.05) in the HT group while BNP values were not. The echocardiographic findings were not correlated with ANP or BNP in the HT patients. This suggests that natriuretic peptides increase is related to the blood pressure elevation rather than LVH to reduce detrimental high BP effects.

[Oxidative stress in end stage renal disease: evidence and association with cardiovascular events in Tunisian patients]. / Stress oxydant chez les insuffisants rénaux chroniques: evidence et association avec les maladies cardiovasculaires chez des urémiques Tunisiens.

We assessed oxidative stress in 35 chronic renal failure under conservative treatment (CRF), 50 hemodialysed (HD) and 30 renal transplant (RT) patients, and 31 age- and sex-matched healthy subjects. Compared to controls, CRF patients exhibited significantly higher conjugated dienes (139 +/- 37 versus 121 +/- 22 micromol/l) and LDL oxidation (126 +/- 65 versus 99 +/- 46 micromol/l). Glutathione peroxidase activity was decreased in CRF and HD (5.31 +/- 2.46 and 5.39 +/- 2.32 versus 7.42 +/- 2.72 U/ml in healthy subjects). Superoxide dismutase activity was lower in HD (91 +/- 38 U/ml) and higher in RT patients (132 +/- 33 U/ml) than controls (116 +/- 30 U/ml). Plasma zinc concentrations were significantly decreased in CRF and HD patients and copper concentrations were significantly decreased in TPR. Plasma selenium levels were normal in the three groups of patients. Vitamin A was significantly increased, whereas vitamin E was normal in the 3 groups of patients compared to healthy controls. Total antioxidant status was increased in CRF and HD, but not in RT patients. Patients with cardiovascular disease showed increased serum copper, and significantly decreased glutathione peroxidase activity. This study revealed an oxidative stress in CRF and HD patients that may favour the development of cardiovascular diseases.

Benzene exposure monitoring of Tunisian workers.

To monitor benzene exposure and to check reliability of urinary trans,trans-Muconic Acid (t,t-MA) as a bio-marker of benzene exposure in local conditions, a study was conducted on 30 Tunisian exposed workers (20 tanker fillers and 10 filling station attendants). The analyses were carried out on environmental air and urinary t,t-MA before (t,t-MAA) and at the end of work shift (t,t-MAB). 20 nonoccupationally exposed subjects were also investigated. The average value of environmental benzene concentration was 0.17 ppm. The differences between t,t-MAA and t,t-MAB concentrations and between t,t-MAB and t,t-MA measured in controls (t,t-MAC) were both significant (p < 0.001). Benzene air concentrations were well correlated with t,t-MAB: R = 0.76. In the nonexposed group, average t,t-MA concentrations is significantly higher among smokers than nonsmokers (P < 0.02). Analysis of urinary t,t-MA offers a relatively simple and suitable method for benzene exposure monitoring.

Classical and "non-classical" cardiovascular risk factors in Tunisian patients with end stage renal disease: prevalence and association with cardiovascular events.

This study was aimed to determine the prevalence of several classical and non-classical cardiovascular risk factors, and to test their association with cardiovascular events in Tunisian patients with end-stage renal disease. A total of 35 chronic renal failure, 50 hemodialysed and 30 renal transplant recipient patients and 31 healthy subjects were included. Hypertension, elevated plasma concentrations of total homocysteine, fibrinogen, C-reactive protein, and lipoprotein(a) were highly prevalent in patients, whereas, smoking, hypertriglyceridemia, hypercholesterolemia, hypoHDLemia, and hypoalbuminemia were less common. In univariate analysis, cardiovascular events were associated with age, hypertension, and the top quartile of the total homocysteine and C-reactive protein values. When controlling for several potential confounding factors, cardiovascular events remained associated with age, hypertension (OR, 7.07; 95% CI, 1.76-28.34; P=0.01), and the top quartile of total homocysteine (OR, 10.41; 95% CI, 2.61-41.55; P=0.001) and C-reactive protein (OR, 3.99; 95% CI, 1.06-14.99; P=0.04).

[Osteoporosis and inflammatory bowel disease: prevalence and risk factors in Tunisian patients]. / Ostéoporose et maladies inflammatoires chroniques de l'intestin: prévalence et facteurs de risque chez des malades tunisiens.

OBJECTIVES: The study was aimed to evaluate osteoporosis prevalence in a group of Tunisian patients with inflammatory bowel disease (IBD), to determine its risk factors, and to describe its mechanisms. SUBJECTS AND METHODS: We included 67 IBD patients, 43 patients with Crohn's disease (CD) and 24 with ulcerative colitis (UC). Bone mineral density was measured at the lumbar spine and left femoral neck by dual-energy X-ray absorptiometry. We used T score to express bone loss (osteopenia: -2.5 SD 2 years and active disease tended to be associated with lumbar osteoporosis; the ORs were respectively 4.87 [0.92-25.80] (P=0.06), 4.21 [0.87-20.57] (P=0.06), and 2.33 [0.78-6.67] (P=0.13). No association was found with cumulated dose of steroids even when considering only CD. Patients with osteoporosis showed significant increased CrossLaps and interleukin-6 levels that indicate both high bone resorption and inflammatory activity. CONCLUSIONS: Osteoporosis is frequent in IBD patients, especially in CD patients. Female gender, malnutrition (body mass index <20 kg/m2), disease course (> 2 years) and active disease would be risk factors of bone mineral loss in IBD. Osteoporosis is associated with enhanced bone resorption, that seems be linked to excessive intestinal inflammation.

[Epidemiological features of patients hospitalized in coronary care units at the military hospital, Tunisia, for 1994-1998: preliminary results]. / Caractéristiques des patients hospitalisés dans le service de cardiologie de l'hôpital militaire entre 1994 et 1998: résultats préliminaires de l'etude tunisienne.

The aim of this study was to evaluate the frequency of cardiovascular disease and risk factors associated in patients hospitalised in coronary care units at Military Hospital, Tunis, over the period 1994-1998. The clinical features of 3513 patients (2389 men and 1124 women) on hospital admission were analysed. 47.3% of patients were hospitalised for coronary disease, 12.5% for valvular heart disease, 5.2% for cardiomyopathy, 16.2% for arrhythmia and conduction disturbance, 6.4% for hypertension and 12.2% for other pathologies. With this risk factor profile Tunisia has to implement a national strategy of primary prevention and heart heath promotion in addition to the efforts recently made in secondary prevention of some chronic disease such as hypertension and diabetes.

[Hyperprolactinemia in systemic lupus erythematosus. A prospective study of 38 cases]. / L'hyperprolactinemie au cours du lupus erythemateux systemique. Etude prospective à propos de 38 cas.

OBJECTIVE: To study prospectively the serum prolactin concentrations among patients with systemic lupus erythematosus and their possible relationship to disease activity and manifestations. METHODS: Serum prolactin levels were measured by radioimmunoassay in 38 patients with systemic lupus erythematosus and 22 age matched controls. Patients with known secondary causes for hyperprolactinaemia, such as pregnancy, lactation, prolactinoma and taking medications known to induce prolactin secretion, were excluded from the study. Demographic, clinical and laboratory features of the patients were obtained. Patients were divided into two subgroups according to their disease activity. Mean prolactin levels from both groups were compared using student test, and prolactin from patients with systemic lupus erythematosus was correlated with variables of disease activity, including the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). RESULTS: Mean prolactin levels were higher in patients with systemic lupus erythematosus (15.4) than healthy controls (9.83); however, the difference did not reach statistical significance (p=). Hyperprolactinemia was found in 24 patients with systemic lupus erythematosus and 5 controls. The frequency of hyperprolactinaemia in systemic lupus erythematosus group was higher than healthy controls. No significant difference in mean prolactin levels was found between patients with active versus inactive disease (18.9 vs 18.5). CONCLUSION: Hyperprolactinaemia occurred significantly in patients with systemic lupus erythematosus, but did not correlate with disease activity.

Phenylketonuria is still a major cause of mental retardation in Tunisia despite the possibility of treatment.

BACKGROUND AND OBJECTIVE: Accumulation of phenylalanine following a deficiency of phenylalanine hydroxylase activity generates a brain damage with mental retardation: phenylketonuria (PKU). In the developing countries, where PKU systematic neonatal screening program is not established yet, the management of PKU handicap is not properly carried out. The aim of this study was to estimate the frequency of the PKU diagnosed following clinical features anomalies, to provide information about the untreated PKU patients profile in Tunisia not covered by neonatal screening. Also it is stressed that treated patients have a normal development. PATIENTS AND METHODS: This is a retrospective study of 156 cases of PKU detected in Tunisia over 20 years following symptoms suggestive of inherited metabolic disease. Phenylalaninemia level was performed by fluorometric method. Among them 9 patients were treated. RESULTS: The PKU estimated frequency was 1/7631. The diagnosis mean age was 4 years. The phenylalaninemia mean was 1680 µmol/L; the classical PKU form accounted for 85.3% of cases and the dominant clinical symptoms were: mental retardation (88.2%), motor delays (87.7%), speech difficulties (83.2%) and pigmentation anomalies (61.7%). The treated patients responded to treatment and showed a normal development. CONCLUSION: The establishment of neonatal screening should be a priority to avoid cases of mentally retardation.

Predictors for cardiovascular morbidity and overall mortality in Tunisian ESRD patients: a six year prospective study.

OBJECTIVES: The study was aimed to test the predictive value of several potential cardiovascular factors and markers for non fatal cardiovascular events (CVE) and overall mortality in Tunisian patients with renal failure. SUBJECTS AND METHODS: One hundred and fifteen renal failure patients were followed-up from 2000 to 2006. At enrollment, each patient underwent clinical examination and blood collection for analysis of lipid parameters, albumin, C reactive protein (CRP), parathyroid hormone (PTH), homocysteine and hemoglobin. Multivariate Cox regression models were applied to identify the predictors for non fatal CVE and overall mortality. RESULTS: During the follow up, seventeen patients were lost. Among the 98 remaining patients, 29 presented a non fatal CVE (21.5%) and 15 were deceased (11.1%). In univariate analyses, non fatal CVE were more frequent in smokers and in patients with high PTH concentrations and low HDL levels. Moreover, low albumin concentrations were univariately associated with overall mortality. In the multivariate analysis, non fatal CVE was significantly and independently associated with age [hazard ratio (95% confidence interval), 1.04 (1.01-1.08); p=0.028] and the upper quartile of PTH concentrations [2.68 (1.24-5.81); p=0.013]. Overall mortality was independently predicted by the bottom quartile of albumin concentrations [5.62 (2.02-15.6); p=0.001] and the upper quartile of CRP concentrations [3.20 (1.14-8.79); p=0.027]. CONCLUSION: Advanced age and high PTH levels are the main predictors of CVE, whereas low albumin and high CRP concentrations are the independent predictors of death in Tunisian renal patients. A better control of these factors would greatly increase the patient's survival rates.

Is serum transthyretin a reliable marker of nutritional status in patients with end-stage renal disease?

OBJECTIVE: To test the value of serum transthyretin (TTR) concentration as a nutritional marker in renal patients. METHODS: The study included 115 renal patients, out of which 35 are on conservative treatment, 50 on hemodialysis and 30 renal transplant recipients, and 31 healthy control subjects. Serum TTR, albumin, transferrin, C-reactive protein (CRP) and alpha1 anti trypsine (AAT) were assessed by immunoturbidimetry, and vitamin A by HPLC. Linear regression models were applied to test the association between serum TTR and body mass index (BMI). RESULTS: Serum TTR concentrations were normal, but serum vitamin A, CRP and AAT concentrations were significantly higher in patients. In renal patients, serum TTR was positively and independently related to BMI and was significantly lower in malnourished than well-nourished patients (367+/-91 vs. 417+/-130 mg/L; p=0.05). The risk of serum TTR<300 mg/L was higher in malnourished patients [OR, 4.82 (1.78-13.2); p=0.001]. CONCLUSION: Serum TTR concentrations were at normal range in renal patients despite evidence of malnutrition and inflammation. However, they were related to BMI and were significantly lowered in malnourished patients. Thus, serum TTR would reflect nutritional status in renal patients. However, the cutoff of malnutrition should be raised to 300 mg/L.

Hyperhomocysteinaemia is associated with uveitis but not with deep venous thrombosis in Behcet's disease.

Plasma homocysteine was assessed in Behcet's disease (BD) patients in order to determine the prevalence of hyperhomocysteinaemia in BD and to test its association with clinical manifestations of the disease. The study included 59 patients with BD and 118 age- and sex-matched healthy subjects. Plasma homocysteine, vitamin B(12) and folate were assessed by automated immunoassay methods. Hyperhomo-cysteinaemia was defined as plasma homocysteine >15 micromol/l. Plasma homocysteine concentrations and the prevalence of hyperhomocysteinaemia were significantly higher in BD patients than in controls [median (5th-95th percentile), 11.3 (6.6-28.1) vs. 10.6 (6.6-17.1) micromol/l, and 25.4% vs. 9.3%, respectively]. In BD patients, hyperhomocysteinaemia was related to male gender, disease severity and uveitis [odds ratio (OR), 5.32; 95% confidence interval (CI), 1.43-21.61; p = 0.008], but not to age, smoking, disease activity, deep venous thrombosis, arthritis or neurological involvement. The association between uveitis and hyperhomocysteinaemia persisted (multi-adjusted OR, 7.46; 95% CI, 1.03-54.3; p = 0.05) after adjusting for gender, age, disease activity and duration, smoking, deep venous thrombosis, and serum concentrations of creatinine, vitamin B(12) and folate. Plasma homocysteine should be measured in patients with BD, and the effect of B-vitamin supplementation should be tested in those with hyperhomo-cysteinaemia.

Hyperhomocysteinemia and end-stage renal disease: determinants and association with cardiovascular disease in Tunisian patients.

The study reports on plasma total homocysteine (tHcy) levels in Tunisian patients with chronic renal failure (CRF) and those treated with hemodialysis (HD) and renal transplant (RT). The aims of the study were to identify the determinants of tHcy concentration and to test the association between hyperhomocysteinemia and atherothrombotic disease in end-stage renal disease (ESRD). A total of 35 CRF patients on conservative treatment, 50 HD patients, and 30 RT recipients, and 31 age- and sex-matched healthy subjects were included. Plasma tHcy was assessed by a fluorescent-polarizing immunoassay method. Multivariate analysis was applied to identify the main determinants of tHcy concentration and to assess the relationship between hyperhomocysteinemia and cardiovascular disease. Plasma mean tHcy concentration was significantly increased (p < 0.001) in CRF patients (mean +/- SD) (28.9 +/- 9.8 micromol/l), in HD patients (29.4 +/- 11.1 micromol/l), and in RT (19.3 +/- 6.3 micromol/l) patients compared to controls (11.9 +/- 4.1 micromol/l). Multivariate analysis using GLM ANOVA modeling demonstrated that tHcy was significantly higher in males (p = 0.02), and was related to age (p = 0.008), albumin (p = 0.005), vitamin B12 (p = 0.002), folate (p = 0.00001), and creatinine clearance (p = 0.0008). However, tHcy was not associated with C-reactive protein and did not significantly differ between CRF, HD, or RT patients. The upper quartile of tHcy concentration was significantly associated with atherothrombotic cardiovascular disease (unadjusted odds ratio (OR) = 3.09; 95% CI, 1.11-8.61; p = 0.01). This association remained significant after adjusting for sex, age, hypertension, and smoking (multi-adjusted OR = 4.78; 95% CI, 1.92-11.9; p = 0.0008). The mean tHcy concentration was 2 to 3 times higher in ESRD patients than in subjects with normal renal function. This increase could be related to glomerular filtration rate reduction and functional B vitamins deficiency, but was not associated with inflammation. The upper quartile of tHcy concentrations confers 4.78-fold increased independent risk for atherothrombotic events in ESRD patients.