Naziha Kaabachi

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.

Clinical and pathological study of three Tunisian siblings with L-2-hydroxyglutaric aciduria

This report describes three brothers belonging to a consanguineous family suffering from a progressive neurological disorder associated with L-2-hydroxyglutaric aciduria. Clinically this disorder is characterized by childhood onset, pyramidal signs, cerebellar and pseudobulbar syndromes and epilepsy. Pathological examination of the brain in the oldest patient, who died at the age of 30 years, showed bilateral and diffuse spongiosis with notable cystic cavitations of the cerebral white matter without abnormal storage in neurons and glial cells. We consider that these findings are related to L-2 hydroxyglutaric aciduria. To our knowledge this present case represents the first to be reported with neuropathological examination.

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.

The metabolic syndrome: Prevalence, main characteristics and association with socio-economic status in adults living in Great Tunis

AIMS This study aimed to determine the prevalence of the metabolic syndrome (MetS) and its association with socio-economic status in the population of Great Tunis. METHODS The study included 2712 subjects (1228 men and 1484 women), aged 35-70 years and living in the Great Tunis region, all of whom were recruited between March 2004 and June 2005. The sample was weighted by using the inverse of the response rate according to governorate, district and gender. The MetS was defined according to the National Cholesterol Education Program-Adult Treatment Panel III. RESULTS In the studied population, the overall prevalence of the MetS was 31.2%, and it was significantly more frequently seen in women than in men (37.3% vs 23.9%, respectively; P<0.001), as were abdominal obesity (69% vs 21.6%, respectively; P<0.001), high blood pressure (50.3% vs 43.1%, respectively; P<0.001) and low HDL cholesterol (40.6% vs 33.6%, respectively; P<0.001), the most common characteristics of the MetS. Also, the prevalence of the MetS increased with age in both genders, but more so in women. In those aged greater than 55 years, the prevalence of MetS was 56.7% in women and 30.7% in men. An inverse relationship was observed between level of education and prevalence of the MetS in women, with the highest prevalence being in illiterate women and the lowest in those who were university graduates. CONCLUSION The prevalence of the MetS is markedly high within the population of Great Tunis and especially in women. As these findings predict future increases in cardiovascular disease in these populations, substantial efforts need to be made to fight against obesity and sedentary lifestyles to ameliorate the expected poor health outcomes.

Methylmalonic acidaemia with bilateral globus pallidus involvement: A neuropathological study

A 16-month-old boy was hospitalized because of a 1-day history of severe ketoacidosis with lethargy, hypotonia, vomiting, and important dyspnoea. Organic acid assay by gas chromatography–mass spectrometry confirmed the diagnosis of methylmalonic acidaemia (MMA). On the sixteenth day, he developed an acute extrapyramidal disorder. The CT scan of the brain disclosed bilaterally symmetric lucency of basal ganglia. He died at 17 months of age. Post-mortem neuropathological examination, showed severe necrosis with spongiosis, cystic cavitation and numerous lipid-laden macrophages of the globi pallidi, and mild spongiosis of subthalamic nuclei, mammillary bodies, portion of internal capsule adjacent to globus pallidus, superior cerebellar peduncles and tegmentum of brainstem. Pallidal infarction, a focal ischaemic lesion, demonstrates that ischaemia/energy depletion may be important in the etiology of the neuropathology of MMA.