[Inherited kidney stones: A nephrology center experience]. / Lithiase urinaire héréditaire : expérience d'un service de néphrologie.

INTRODUCTION: Genetic factors must be considered in etiological diagnosis of urinary lithiasis. The aim of this study was to determine clinical, metabolic characteristics and the progression of hereditary urinary lithiasis in our patients. METHODS: A retrospective study was conducted between 2008 and 2018 and 60 patients were included. Patients were referred to our department from pediatrics departments to be followed-up in adulthood in 9 cases, for etiological investigation in 42 cases and for chronic renal failure in 9 cases. RESULTS: Thirty-five men and twenty-five women were enrolled in this study with a M/F sex ratio equal to 1.4. The mean age at the time of diagnosis of the hereditary character of the urinary lithiasis was 28.6years (3months-63years). The average delay between the onset of the lithiasis disease and the etiological diagnosis was 8years (0-42years). We noted 31 cases of cystinuria, 18 cases of primary hyperoxaluria type 1 with two mutations (I244T in 14 cases, 33-34 Insc in 23 cases) and 11 cases of renal tubulopathy. Fourteen patients were affected with chronic renal failure, of which five were in the end-stage renal disease. Crystalluria was positive in 62% of cases. The morpho-constitutional analysis of stones was performed in 37 cases and it contributed to the diagnosis in 29 cases. After an average follow-up of 16years, we noted normal renal function in 42 cases, chronic renal failure in 7 cases, hemodialysis in 10 cases all with primary hyperoxaluria and transplantation in 1 case. CONCLUSION: The etiological diagnosis of hereditary urinary lithiasis in our study was made with considerable delay. Cystinuria was the most frequent etiology and primary hyperoxaluria was the most serious affection. LEVEL OF EVIDENCE: 4.

[Hyperhomocysteinemia and schizophrenia: case control study]. / Hyperhomocystéinémie et schizophrénie : étude cas-témoin.

OBJECTIVES: Homocysteine (Hcys) is a sulphur-containing amino acid that has been widely investigated for its putative role in neuropsychiatric disorders. Elevated plasma homocysteine levels have been associated with schizophrenia. Among other factors, low folate and vitamin B12 levels have been implicated in the increase in homocysteine. The aim of the study was to determine plasma Hcys, folate and vitamin B12, and the frequency and severity of hyperhomocysteinemia in patients with schizophrenia, and to investigate the association between Hcys and clinical features and its relationship with folate and vitamin B12 levels. METHODS: This was a case-control study carried out on 61 (54 males and seven females, mean age=33.3 ± 9.2) inpatients with chronic schizophrenia according to DSM-IV criteria and 46 (25 males and 21 females, mean age=45.9 ± 14.2) healthy controls. Most of patients (90.2%) were treated by first generation antipsychotics with a mean daily dosage of 401.6 mg chlorpromazine equivalents. Total homocysteine serum levels were determined quantitatively by fluorescence-polarization immunoassay (FPIA) with an AxSYM analyzer™ (Abbott). Quantitative vitamin B12 and folate serum levels were measured with an Elecsys 2010 analyzer™ (Roche Diagnostics). Differences between patients and controls were examined using a two-way Ancova with gender and diagnosis as independent variables, adjusting for age. RESULTS: Patients with schizophrenia showed higher plasma Hycs and lower plasma folate than controls (mean=16.1 µmol/L in patients versus 10.9 µmol/L in controls; P=0.028 for Hycs and 4.2 µg/L in patients versus 8.2 µg/L in controls; P<0.001 for folate). Patients and controls did not differ in vitamin B12 levels. Both male and female patients had increased plasma Hcys compared to controls. Hyperhomocysteinemia (Hcys levels>15 µmol/L) was present in 34.4% of the patients versus 15.2% in controls. The prevalence of moderate hyperhomocysteinemia (Hcys levels: 15-29 µmo/L) was 26.2% and that of intermediate hyperhomocysteinemia (Hcys levels: 30-100 µmol/L) was 8.2%. In patients with schizophrenia, plasma Hcys was not correlated with age (r=0.07; P=0.56), duration of illness (r=-0.04; P=0.78) and did not differ with gender and clinical sub-types. Moreover, plasma Hcys was higher in patients without family history of psychiatric disorders (19.2 µmol/L) versus 12.7 µmol/L in patients with family history of psychiatric disorders (P=0.032). Concerning therapeutic features, plasma Hcys did not differ with type of antipsychotic and was not related to daily dosage of antipsychotics. A negative correlation was found between plasma Hcys and vitamin B12 levels (r=-0.26; P=0.04). CONCLUSION: These results confirm an increase of Hcys levels in schizophrenic patients and suggest that it is associated with absence of family history of psychiatric disorders and with low vitamin B12 levels. Hyperhomocyteinemia could be related to the pathophysiology of aspects of this illness. Homocysteine should be considered as a factor to consider in monitoring and management of patients with schizophrenia.

[Effect of polymorphisms on key enzymes in homocysteine metabolism, on plasma homocysteine level and on coronary artery-disease risk in a Tunisian population]. / Effet des polymorphismes des enzymes clés du métabolisme de l'homocystéine sur l'homocystéinémie et le risque coronarien chez une population tunisienne.

BACKGROUND: Hyperhomocysteinemia is known as an independent-risk factor for coronary-artery disease (CAD). However, the effect of homocystein metabolic enzymes polymorphisms on CAD is still controversed. We investigated the relation between homocystein metabolic key enzymes polymorphisms, homocystenemia and coronary stenosis in a Tunisian population. METHODS: Samples were collected from 251 CAD patients documented by angiography. Genotyping were performed for C677T methylene-tetrahydrofolate reductase (MTHFR), A2756G methionine-synthase (MS) and 844ins 68 cystathionine-beta-synthase (CBS). We measured fasting plasma tHcy, folate and vitamin B12. RESULTS: There was significant increase in homocysteinemia for homozygous genotypes of C677T MTHFR (p<0.001) and A2756G MS (p=0.01), but not for 844ins68 CBS (p=0.105). Potential confounders adjusted odds-ratios for significant coronary stenosis, associated with MTHFR TT, MS GG and CBS insertion, were respectively 1.78 (p=0.041); 2.33 (p=0.036) and 0.87 (p=0.823). The effect of mutated MTHFR genotype was more pronounced on homocysteinemia (21.4+/-9.1 micromol/L; p<0.001) and coronary stenosis (OR=2.73; p=0.033) at low folatemia (< or =6.1 ng/mL). CONCLUSION: MTHFR TT and MS GG genotypes increase tHcy concentration and coronary stenosis risk, especially with low folatemia.

Profile of drug resistance mutations among HIV-1-infected Tunisian subjects failing antiretroviral therapy.

Three years after the introduction of antiretroviral therapy (ART) in Tunisia (North Africa), we aimed to determine the prevalence of drug resistance mutations in Tunisian HIV-1-infected patients failing ART. Plasma samples of 80 patients were tested for genotypic resistance using two distinct line probe assays, LiPA HIV-1 reverse transcriptase RT and LiPA HIV-1 protease assay. Of the 80 patients, 82.5% showed resistance to at least one antiretroviral molecule. In the RT gene, resistance to nucleoside RT inhibitors (NRTIs) and non-nucleoside RT inhibitors (NNRTIs) were recognized in 66.25 and 37.5%, respectively, with M184V, T215Y and K103N being the codons most frequently involved. Resistance to protease inhibitors (PIs) was found in 46.25% of cases. Despite the presence of different mutations, the viral variants were still susceptible to other RTIs and PIs that are currently not available in Tunisia. Thus, alternative therapeutic options exist but are not yet accessible.

[Arachidonate to saturated fatty acid ratio of circulating sterides and phospholipids: can it be risk marker of coronary stenosis? A Tunisian study]. / Le rapport arachidonate sur acides gras saturés des stérides et des phospholipides circulants: peut-il être un témon du risque de sténose coronarienne? Etude dans une population tunisienne.

The prevention and early diagnosis of cardiovascular diseases is a public health priority in Tunisia and actions are undertaken to evaluate biologic marquers in at risk populations. Concentrations of fatty acids in serum phospholipids and sterides have been measured using thin layer chromatography and gaz chromatography of transmethyled derivatives. The study concerned 98 coronarographed patients, presenting (n = 72) or not coronary artery disease (n = 26). The results have been compared to those of a reference population (n = 43) without any cardiac pathology. The mean concentrations of most of sterides fatty acids in coronarographed patients were higher than in controls, except for arachidonic acid which was slightly lower (68 +/- 34 mg/L versus 77 +/- 19,6 mg/L in controls). Considering concentrations of sterides fatty acids in the two subgroups of patients, coronary artery disease was associated with an increase of all these fatty acids, which was statistically significant for palmitate, linoleate and linolenate. Measurements of fatty acids in phospholipids showed a reduction of arachidonic acid in coronarographed patients (76 +/- 36,7 mg/L versus 135 +/- 49,3 mg/L in controls), but without correlation with the severity of the stenosis.