Moncef Feki

Fecal calprotectin is a predictive marker of relapse in Crohn's disease involving the colon: a prospective study

Objectives Fecal calprotectin seems to have a diagnostic precision in predicting relapse in quiescent ulcerative colitis patients. However, the data remain controversial in Crohns disease. The aim of this study was to prospectively evaluate the role of fecal calprotectin as a predictive marker for 1-year follow-up in patients with asymptomatic Crohns disease. Methods Fifty-three Crohns disease patients in clinical remission were consecutively included providing at the beginning of the study a single stool sample as well as a blood sample and regularly followed-up for 12 months. Fecal calprotectin level was measured using a commercially available enzyme-linked immunoassay. Results Among 53 patients, 10 (18.9%) developed clinical relapse during the 12-month follow-up period. Median fecal calprotectin level was significantly higher in relapse group patients compared with that in nonrelapse group (380.5 vs. 155 μg/g, P<0.001). With a cutoff value of 340 μg/g fecal calprotectin gave sensitivity of 80% and specificity of 90.7% in predicting clinical relapse. Fecal calprotectin level greater that 340 μg/g gave an 18-fold higher risk to develop relapse (log rank P<0.001) and was found to be an independent predictive factor of relapse (P=0.02). Conclusion Fecal calprotectin seems to be a reliable marker of relapse in quiescent Crohns disease patients.

Creatine and Creatine Deficiency Syndromes: Biochemical and Clinical Aspects

Creatine deficiency syndromes, which have only recently been described, represent a group of inborn errors of creatine synthesis (L-arginine-glycine amidinotransferase deficiency and guanidinoacetate methyltransferase deficiency) and transport (creatine transporter deficiency). Patients with creatine deficiency syndromes present with mental retardation expressive speech and language delay, and epilepsy. Patients with guanidinoacetate methyltransferase deficiency or creatine transporter deficiency may exhibit autistic behavior. The common denominator of these disorders is the depletion of the brain creatine pool, as demonstrated by in vivo proton magnetic resonance spectroscopy. For diagnosis, laboratory investigations start with analysis of guanidinoacetate, creatine, and creatinine in plasma and urine. Based on these findings, enzyme assays or DNA mutation analysis may be performed. The creatine deficiency syndromes are underdiagnosed, so the possibility should be considered in all children affected by unexplained mental retardation, seizures, and speech delay. Guanidinoacetate methyltransferase deficiency and arginine-glycine amidinotransferase deficiency are treatable by oral creatine supplementation, but patients with creatine transporter deficiency do not respond to this type of treatment.

Electrophysiological and nerve biopsy: comparative study in Friedreich's ataxia and Friedreich's ataxia phenotype with vitamin E deficiency

Abstract The authors report a comparative study of peripheral nerve conductions and nerve biopsy and somatosensory evoked potentials between 15 patients with Friedreichs ataxia and 15 patients with Friedreichs ataxia phenotype with selective vitamin E deficiency. The patients in the two groups are of similar age, age of onset, and clinical phenotype. Peripheral motor nerve action potential amplitude, and conduction velocities are within normal ranges in the two groups. In the Friedreichs ataxia group there is an early and severe peripheral sensory axonal neuronopathy, characterised by an important reduction of the amplitude of sensory action potential, and important loss of myelinated fibres with complete disappearance of large myelinated fibres without any regenerative process. In the Friedreichs ataxia phenotype with selective vitamin E deficiency group there is slight-to-moderate axonal sensory neuropathy with normal to moderate decrease of large myelinated fibre density and important regeneration in nerve biopsy. Somatosensory evoked potentials are markedly involved in the two groups asserting a severe involvement of somatosensory pathway in lumbar, thoracic and cervical spinal cord. These findings suggest that the pathological mechanism involved in the two diseases are different: central peripheral axonopathy in Friedreichs ataxia and central distal axonopathy in Friedreichs ataxia phenotype with selective vitamin E deficiency.

Metabolic syndrome in Tunisian psoriatic patients: prevalence and determinants.

Background  A significant association between psoriasis and the metabolic syndrome (MetS) has been frequently reported.

Gender-specific effect of Pro12Ala polymorphism in peroxisome proliferator-activated receptor γ-2 gene on obesity risk and leptin levels in a Tunisian population

OBJECTIVES This study was undertaken to investigate the impact of the Pro12Ala (rs1801282) polymorphism of the peroxisome proliferator-activated receptor gamma-2 (PPARgamma-2) gene on obesity or body mass index (BMI) and plasma leptin, insulin, adiponectin and lipid levels in a sample of the Tunisian population. DESIGN AND METHODS The study included 387 obese patients and 288 control subjects. The Pro12Ala genotype was determined by polymerase chain reaction followed by a digestion with the restriction of endonuclease BstUI. RESULTS In the whole population, there is no significant difference in genotype frequencies of the Pro12Ala polymorphism between obese patients and controls. However, separate analysis by gender revealed that obese men (but not women) had significantly higher frequency of Pro/Ala genotypes compared to controls (12.2% vs. 4.1%; chi(2)=6.76, p=0.009). In comparison to Pro/Pro homozygotes, Ala-allele bearers had a significantly higher risk of obesity [OR (95% CI)=3.26 (1.28-8.33)]. When obese subjects were stratified according to type 2 diabetes status, the association with obesity was only significant in obese non-diabetic patients [OR (95% CI)=3.74 (1.43-9.74), p=0.007]. Additionally, obese male patients carrying the Ala-allele had significantly higher body mass index (p=0.007) and plasma leptin levels (p=0.023) compared to those homozygous for Pro-allele. The significant effect of Pro12Ala polymorphism on plasma leptin levels disappeared after adjustment for age and BMI. CONCLUSION The present study provides evidence that the Pro12Ala polymorphism of the PPARgamma-2 gene is associated with obesity in non-diabetic men from Tunisian origin.

Association of G-2548A LEP polymorphism with plasma leptin levels in Tunisian obese patients.

OBJECTIVES The aim of this study was to examine the association of the G-2548A polymorphism of the human leptin gene (LEP) with body mass index (BMI), plasma leptin, insulin, and lipid parameters in a sample of Tunisian population. DESIGN AND METHODS Two hundred and twenty nine obese patients (BMI>or=30 kg/m(2)) were screened and compared to 251 normal weight subjects (BMI<25 kg/m(2)). The human leptin gene promoter G-2548A genotype was determined by polymerase chain reaction followed by a digestion with the restriction of endonuclease CfoI. RESULTS In the entire study sample, carriers of -2548A allele had significantly lower leptin levels than homozygous for -2548G allele (14.28+/-9.10 ng/mL vs. 18.27+/-12 ng/mL, p<0.001 respectively) adjusted for BMI and gender. In obese patients but not control, subjects carrying the -2548A allele exhibited lower leptin levels than those with GG genotype (16.96+/-8.27 ng/mL vs. 21.37+/-11.72 ng/mL, p=0.001 respectively) adjusted for BMI and gender. In this group, carriership of the -2548A allele was identified, by multiple linear regression models, as significant independent predictor for leptin levels variability. Separate analyses by gender revealed that only in obese women, the -2548A allele was found to be associated with lower leptin levels independently of BMI (p=0.004). CONCLUSIONS The present study showed that G-2548A LEP polymorphism is associated with lower leptin levels in Tunisian obese women.

LEPR p.Q223R Polymorphism Influences Plasma Leptin Levels and Body Mass Index in Tunisian Obese Patients

BACKGROUND AND AIMS The leptin receptor (LEPR) plays a crucial role in the regulation of body weight. Several common polymorphisms have been described in the human LEPR gene including the p.Q223R polymorphism (rs1137101). The association of this polymorphism with obesity or related metabolic phenotypes has been controversial. The aim of this study was to investigate the impact of the LEPR p.Q223R polymorphism on body mass index (BMI), plasma leptin and lipid parameters in a sample of the Tunisian population. METHODS The study included 391 obese patients and 302 normal weight subjects. LEPR p.Q223R genotypes were identified by the PCR-RFLP analysis. RESULTS Obese patients homozygous for RR genotype showed lower leptin levels than those with other genotypes (p = 0.005) adjusted for age, BMI and gender. Stratified analysis by gender revealed that obese male patients carrying the R allele showed significantly lower BMI (p = 0.007) and leptin levels (p = 0.037) than subjects homozygous for the Q allele. In obese women, the LEPR p.Q223R polymorphism was found associated with lower leptin concentrations (p = 0.05). After adjustment for age and BMI, the association between the LEPR variant and plasma leptin remained significant only within female patients (p = 0.027). A general linear model including leptin as dependant variable and age, BMI, menopausal status and genotype as covariates revealed that the LEPR p.Q223R polymorphism is independently associated with leptin levels in obese women (p = 0.026). CONCLUSIONS Our findings suggest that the LEPR p.Q223R polymorphism influences plasma leptin levels and BMI in obese patients.

Association between the − 2518G/A polymorphism in the monocyte chemoattractant protein-1 (MCP-1) gene and myocardial infarction in Tunisian patients

BACKGROUND Monocyte chemoattractant protein-1 (MCP-1; gene name CCL2) has been suggested to play an important role in the initiation of atherosclerosis by recruiting monocytes to sites of injured endothelium. Recently, single nucleotide polymorphisms (SNPs) in the MCP-1 regulatory region have been identified. Controversial results regarding the association of the -2518G/A polymorphism of the MCP-1 gene with coronary artery disease (CAD) have been reported. In the present study, we examined a possible association between the -2518G/A polymorphism of the MCP-1 gene and myocardial infarction (MI) in a sample of the Tunisian population. METHODS A total of 319 Tunisian patients with MI and 467 healthy controls were included in the study. The SNP of the MCP-1 gene was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS Patients with MI had significantly higher frequency of the AG+GG genotypes compared to controls [42.9% vs. 35.8%; OR (95%CI), 1.34 (1.00-1.79); p=0.04]. The MI patient group showed a significant higher frequency of the G allele compared to the controls [0.242 vs. 0.195; OR (95%CI), 1.31(1.02-1.68), p=0.03]. The association between the -2518G/A polymorphism of the MCP-1 gene and MI was no longer significant after adjustment for other well-established risk factors. CONCLUSION The present study showed a significant but not independent association between the -2518G/A polymorphism of the MCP-1 gene (presence of G allele) and MI in the Tunisian population.

Prévalence des facteurs de risque cardiovasculaires conventionnels dans la population du Grand Tunis

BACKGROUND This study was designed to determine the prevalence of main cardiovascular risk factors in the population of Great Tunis. SUBJECTS AND METHODS This cross-sectional study included 2483 individuals aged 35 to 70 years dwelling in the Great Tunis region, recruited between March 2004 and June 2005. The sample was weighted using the inverse of response rate according to governorate, district and sex. RESULTS Obesity and abdominal obesity were observed respectively in 34 and 48% of subjects. The prevalence of these two factors was particularly elevated in females (46 and 69% respectively). Hypertension was common (31%), especially in women (36%). Diabetes mellitus and dyslipemia were found in 15 and 21% of subjects, respectively, without difference according to sex. More than half of men and 8% of women were current smokers. CONCLUSION The prevalence of conventional cardiovascular risk factors is dramatically high in the population of Great Tunis. These findings predict a future expansion of cardiovascular diseases in this population. Profound changes of lifestyle and dietary habits of Tunisians are needed to reduce the risk of cardiovascular morbidity and mortality.

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

Abstract Plasma homocysteine was assessed in Behçets 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 B12 and folate were assessed by automated immunoassay methods. Hyperhomo-cysteinaemia was defined as plasma homocysteine >15μmol/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)μmol/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 B12 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.