[Lineage assignment in acute leukemia: confrontation between cytology and immunophenotyping]. / Diagnostic de lignée dans les leucémies aiguës : confrontation entre cytologie et immunophénotypage.

OBJECTIVE: The determination of the cellular lineage in acute leukemia is a crucial step in the diagnosis and the later therapeutic conduct. In Tunisia, emerging country, some cases of acute leukemias are still treated on the basis of an only cytologic study because of lack of cytometry. Our objective is to realize a confrontation between cytology and flow cytometry in the diagnosis of AL and to analyze discrepancies. PATIENTS AND METHODS: The study concerns 100 cases of AL. A second double-blind examination of the bone marrow smears of acute leukemias is realized by two cytologists and confronted to immunophenotyping. RESULTS: In two cases of AML, flow cytometry reassigned lineage into T ALL and biphenotypic AL. In three cases of ALL the lineage was reassigned into undifferentiated acute leukemia (2 cases) and biphenotypic acute leukemia (1 case). Lineage was not established in four cases, immunophenotyping allowed the diagnosis of B ALL in 3 cases, and of biphenotypic acute leukemia in 1 case. In both cases of discrepant findings, flow cytometry allowed the diagnosis of biphenotypic acute leukemia in a case and of AML in the other one. CONCLUSION: The cytological study remains insufficient in the diagnosis of lineage even with experimented cytologists. Immunophenotyping is essential in lineage assignment and reassignment.

[Causes of death in Tunisia: estimates of years of life lost]. / Causes de décès en Tunisie : estimation des années de vie perdues.

This study estimated the number of years of life lost (YLL) by cause due to premature death in Tunisia for the year 2006. We adopted the methodology (SEYLL) proposed by Murray and Lopez. The crude rate of YLL was 58.1 per 1000 inhabitants. After age-standardization using the world population, we obtained a rate of 57.7 YLL per 1000. Cardiovascular diseases (CVD) (19.3% of total YLL) and cancers (17.8%) dominated the burden of premature mortality, followed by perinatal conditions (13.6%). Excluding extreme age groups where perinatal conditions (0-4 years) and CVD (> 60 years) dominated the YLL's causes, injuries (road traffic crashes, falls, etc.) and cancers were most responsible for YLL. The present study highlights the major contribution of noncommunicable diseases to YLL in Tunisia. The promotion of healthy lifestyle and the reinforcement of secondary prevention in primary health care are the best ways to tackle these diseases.

Y402H polymorphism in complement factor H and age-related macular degeneration in the Tunisian population.

To evaluate a possible association between the complement factor H (CFH) Y402H polymorphism and susceptibility to age-related macular degeneration (AMD) in the Tunisian population, as well as the impact of the genotype distribution among different phenotypes and the response to treatment with intravitreal bevacizumab, exon 9 of CFH was analyzed for the Y402H polymorphism by direct sequencing in 135 healthy controls and 127 sporadic unrelated AMD patients classified into the following groups: 12 atrophic AMD (group G1), 115 exudative AMD (G2) and 10 AMD patients who had fibrovascular scarring (G3) that did not allow a precise grading of the phenotype. Seventy patients in G2 were treated with 1.25 mg intravitreal bevacizumab at 6-week intervals until choroidal neovascularization (CNV) was no longer active. The frequency of the CFH 402H allele was significantly higher in AMD patients than in controls (p = 2.62 × 10(-16)). However, subgroup analysis does not reveal any association between the variant allele H and phenotypes of AMD or CNV. Also, there was no significant difference in response to bevacizumab treatment according to Y402H CFH genotype (p = 0.59). A strong association of the 402H allele with susceptibility to AMD in the Tunisian population was confirmed; however, this variant does not appear to be involved in the clinical progression of this disease or in the postintravitreal bevacizumab response.

[Reasons for using emergency departments of major hospitals in Greater Tunis]. / Motifs du recours aux services d'urgence des principaux hôpitaux du Grand Tunis.

Tunisia, similar to many countries, has a problem of overcrowding of the emergency departments (ED). This study aimed to analyse the reasons for using EDs, and to describe the seriousness of the attendees' condition and their itinerary before their arrival at ED. This cross-sectional study in 2009 was conducted in ED of 4 hospitals in GreaterTunis and targeted 1058 patients of both sexes, aged 18 years, with stratification according to time of day of presentation to ED (morning, afternoon and evening). Information was recorded on the sociodemographic characteristics of the study participants, reasons for choosing ED, time of and reason for consultation, diagnosis and severity of illness. Over half the patients (52.5%) were male and the mean age was 46.0 (SD 18.1) years. The main reasons for choosing the ED were: speed (54.0%) and ease of access (47.7%) of ER and occurrence of an acute episode (26.4%). Patients with serious illness accounted for only 6.3% of those interviewed. Implementation of good practices and better coordination between public and private services and the ED are needed to reduce unnecessary visits to ED.

Soluble human leukocyte antigen-G (SHLA-G) in Tunisian kidney transplantation.

To investigate the relationship between the soluble HLA-G (sHLA-G) and the appearance of acute renal rejection (AR) episodes we have quantify in this study the level of sHLA-G by enzyme-linked immunosotrbent assay in 42 kidney transplant patients classified in two groups: G1: 17patients with acute rejection (AR+) and G2: 25 patients without AR (AR-). To establish our normal sHLA-G ranges, serum samples from 18 healthy controls were tested. Pre-transplantation sHLA-G levels were significantly increased in patients (mean +/- standard error of the mean, 60.48 +/- 12.18 units/ml) than healthy subjects (19.11 +/- 4.9 units/ml) (p = 0.001). Although the difference was not statistically significant, G1 patients (AR+) revealed lower levels of sHLA-G (mean +/- standard error of the mean, 31.25 +/- 6.71 units/ml) compared to G2 patients (AR-) (53.43 +/- 1721 units/ml). Nevertheless, the course of total sHLA-G levels was nearly identical in patients with and without rejection. Nonparametric analysis revealed that pre-transplantation levels of sHLA-G < 18.00 units/ ml (sensitivity: 87.8% and specificity of 72.2%) were not related to rejection. Also, multivariate analysis regarding anti-HLA antibody status, recipient age and gender showed that sHLA-G could not be an independent risk factor for renal graft rejection. However, a higher sera levels of sHLA-G seemed to contribute to better kidney allograft survival rate after 10 years of follow-up (significance tendency: p = 0.091) as shown by the survival analysis. Because of the small number of subjects studied, these results must be treated with caution. A much larger cohort of kidney transplant patients according to acute rejection would seem necessary to confirm these findings.

Association of chemokine and chemokine receptor polymorphisms with activity degree of IBD in Tunisian patients.

Crohn's disease (CD) and ulcerative colitis (UC) have complex genetic background that is characterised by more than one susceptibility locus. To detect a possible association between the functional polymorphisms of the chemokine receptors CCR5, CCR2 and MCP-1 genes and susceptibility to CD and UC in Tunisian population, polymorphisms of CCR5-delta32, CCR5-59029-A/G, CCR2-V641 and MCP-1-2518-G/A were analysed in 194 Inflammatory bowel disease (IBD) patients and 169 healthy blood donors using PCR-RFLP and PCR-SSP methods. The patients were classified in 126 patients with CD and 68 patients with UC. The genotypic and allelic frequencies of all polymorphisms studied, did not reveal significant differences between patients and conrols and among CD and UC patients. However, analysis of CD patients revealed that those without homozygosous G/G genotype are more frequently in remission compared to those with this genotype (OR: 0.4, 95% CI: [0.174-0.928]; p = 0.03). Also, the frequency of the CCR2-641 muted allele was statistically higher in CD patients in remission disease than those in active form (OR: 0.267 95% CI: [0.09-0.78]; p = 0.01). Adjustment for known covariates factors (age, gender and immunosuppressive regimen) confirmed these univariate findings and revealed that the CCR5-59029-A/G and CCR2-V64I genotype were associated to remission form of CD (OR: 263; 95% CI: [1.01-6.80]; p = 0.047 and OR: 4.64; 95% CI: [1.01-21.31]; p = 0.049 respectively). In conclusion, the present study supports the involvement of chemokine receptor (CCR2 and CCR5) polymorphisms in activity degree of the IBD disease in Tunisian patients.

[Cost effectiveness analysis of screening strategies for cervical cancer in Tunisia]. / Analyse coût-efficacité des stratégies de dépistage du cancer du col utérin en Tunisie.

We aimed to identify the most appropriate screening strategy for cervical cancer (periodicity of 3, 5 or 10 years) for Tunisia, taking into consideration the incidence of the disease, costs of screening and economic implications. We simulated follow-up of a fictitious cohort of 1 million women 35-39 years over 30 years. Computation of yearly medical care costs was based on data from medical files of patients diagnosed with cervical cancer in 2004 at the National Institute of Cancer, Tunis. For a 60% coverage level of screening, cervical cancer reduction would be 49.2% for a 3-year periodicity. The reduction would be 40.3% and 33.1% for 5 and 10 years periodicity respectively. Considering cost-effectiveness, 10-year screening gave the lowest annual cost to avoid 1 cervical cancer case.

[Neurological abnormalities in xeroderma pigmentosum]. / Les atteintes neurologiques au cours du xeroderma pigmentosum.

INTRODUCTION: Xeroderma pigmentosum (XP) is an autosomal recessive disease characterized by abnormal sensitivity to sunlight which results in pigmentary changes, telangiectases, keratoses and eventually carcinomata. Additional neurological complications can be associated. The aim of our study was to analyze particularities of neurological abnormalities of Tunisian patients. METHOD: We conducted a retrospective study in 62 patients suffering from XP included during the period 1992-2007. Patients were aged from 1 to 64 years (mean age: 17.6 +/- 11.4 years). Thirty patients were female and 32 were male. The patients had severe (n=16), variant (n=15) and moderate (n=31) XP. RESULTS: Neurological abnormalities were observed in 21 patients (33.9%). Mental retardation was observed in 15 of the 21 patients, pyramidal syndrome in five, cerebellar syndrome in two, extrapyramidal syndrome in two, microcephalia in two, choreoatetosis in three cases and a peripheral neuropathy in eight. No neurological disorder was observed in the XP-variant patients. Neurological abnormalities were more frequent in the patients with moderate XP (n=17, 64.5%) than with severe XP (p=0.051). CONCLUSION: This difference in a group of Tunisian patients confirms the heterogeneous nature of XP and is probably due to genetic heterogeneity.

[Study of association of the SNP19 polymorphism of calpain 10 gene with type 2 diabetes in ethnic sub-groups of the Tunisian population: gene-environment interaction]. / Etude de l'association du polymorphisme SNP19 du gène calpaïne 10 avec le diabète de type 2 chez deux groupes ethniques dans la population tunisienne : interaction gène-environnement.

Calpaïn 10 (CAPN10) is the first diabetes gene to be identified through a genome scan followed by positional cloning, encoding the cysteine protease, the calpaïn 10 encodes for a ubiquitously expressed protease implicated in the two fundamental pathophysiological aspects of T2DM insulinoresistance and insulinosecretion. Many investigators, but not all, have subsequently found association between calpaïn 10 polymorphism and type 2 diabetes (T2DM) as well as insulin action and insulin secretion. The aim of this study was to determine whether there is an association between specific polymorphism SNP19 in CAPN10 gene and T2DM in two ethnic groups from Djerba Island. Overall, 162 patients with type 2 of diabetes and 110 healthy volunteers who served as controls for genetic characterization with no family history of diabetes were included in the present study. They consisted of 159 women and 113 men. Their mean +/- SD age was 56,47 +/- 11,86 years. All subjects were genotyped according to SNP 19 polymorphism in CAPN10 gene with PCR method to perform case-control study. After adjusting for gender and age, we found an association with a high risk of T2DM in Djerba Island only in Arab sub-group.

Health and behaviours of Tunisian school youth in an era of rapid epidemiological transition.

To assess youth health behaviours and related quality of life in urban Tunisia, we conducted a cross-sectional survey of a representative sample of 699 secondary-school students. The overweight rate was 20.7%. Most of the sample had an insufficient level of physical activity and were unfamiliar with the recommended frequency of moderate physical activity. Norm-based scores of psychological state were about average, slightly better for boys than girls. Girls perceived themselves to be more stressed than boys. Of all students, 35% declared having smoked a cigarette and 14% having drunk alcohol at least once in their lives. The main sources of health education were mass media (59%) and medical staff (36%).

Blastomyces dermatitidis in a Renal Transplant Recipient: A Case Report.

Fungal infections have an important role in organ transplant recipients, and in some cases can be lethal. Blastomycosis is rare in kidney transplantation. We present a case of cutaneous blastomycosis in a kidney transplant recipient in Tunisia, a country outside the known endemic countries. This case, with the very uncommon and unexpected diagnosis of blastomycosis, demonstrates the diversity of infections in transplant recipients and reflects the importance of histologic and serologic tests in the immunocompromised patient.

Assessment of cardiovascular risk in Tunisia: applying the Framingham risk score to national survey data.

OBJECTIVE: This paper aims to assess the socioeconomic determinants of a high 10 year cardiovascular risk in Tunisia. SETTING: We used a national population based cross sectional survey conducted in 2005 in Tunisia comprising 7780 subjects. We applied the non-laboratory version of the Framingham equation to estimate the 10 year cardiovascular risk. PARTICIPANTS: 8007 participants, aged 35-74 years, were included in the sample but effective exclusion of individuals with cardiovascular diseases and cancer resulted in 7780 subjects (3326 men and 4454 women) included in the analysis. RESULTS: Mean age was 48.7 years. Women accounted for 50.5% of participants. According to the Framingham equation, 18.1% (17.25-18.9%) of the study population had a high risk (≥20% within 10 years). The gender difference was striking and statistically significant: 27.2% (25.7-28.7%) of men had a high risk, threefold higher than women (9.7%; 8.8-10.5%). A higher 10 year global cardiovascular risk was associated with social disadvantage in men and women; thus illiterate and divorced individuals, and adults without a professional activity had a significantly higher risk of developing a cardiovascular event in 10 years. Illiterate men were at higher risk than those with secondary and higher education (OR=7.01; 5.49 to 9.14). The risk in illiterate women was more elevated (OR=13.57; 7.58 to 24.31). Those living in an urban area had a higher risk (OR=1.45 (1.19 to 1.76) in men and OR=1.71 (1.35 to 2.18) in women). CONCLUSIONS: The 10 year global cardiovascular risk in the Tunisian population is already substantially high, affecting almost a third of men and 1 in 10 women, and concentrated in those more socially disadvantaged.

[A multicenter study on profile of hypertension in focal segmental glomerulosclerosis in Tunisia]. / Profil de l'hypertension artérielle dans la hyalinose segmentaire et focale (HSF). Étude multicentrique de 116 cas en Tunisie.

UNLABELLED: Hypertension in focal segmental glomerulosclerosis is frequent and responsible for the progression of the disease. It could be a circumstance of the diagnosis of FSG or a complication of the nephrotic syndrome. PURPOSE: To determine the prevalence of hypertension among patients with FSG diagnosed in Tunisia and to describe the profile of patients with FSG having hypertension in contrast with who do not. PATIENTS AND METHODS: It was a retrospective multicentric study based on 116 patient files having FSG located in 5 specialized centers in Tunisia. RESULTS: The prevalence of hypertension among our patients was 41%, with a feminine predominance, their mean age was 36.34 ± 15.71 years. The systolic blood pressure among the patients with hypertension was 153.18 mmHg. The nephrotic syndrome was impure due to hypertension in 14.5% of the cases. The patients affected by hypertension were more obese. Proteinuria was higher among those not having hypertension than those with it, who score an average value of 5.67 ± 4.51 g/24h, with an insignificant difference. Serum creatinine at presentation was significantly higher among patients with hypertension. Vascular lesions were present at the renal biopsy among 39.45% of patients affected by hypertension, associated with renal failure in 58.50% of patients. The etiopathogenic treatment of FSG was essentially based on steroids full dose. CONCLUSION: Hypertension is often present in FSG and its' treatment must be as soon as possible in order to slow the progression of kidney chronic disease.

Histologic features of chronic allograft nephropathy revealed by protocol biopsies in kidney transplant recipients.

BACKGROUND: The aim of the present study was to describe the histologic features disclosed by protocol kidney transplant biopsies in patients who experienced neither acute rejection nor acute renal failure during the 2 years after transplantation. METHODS: We studied 10 recipients of HLA-identical kidneys from living-related donors and 31 recipients of cadaveric kidneys. They were selected because, during the 2 years after transplantation, they did not experience clinical acute or chronic rejection, their renal function was normal and stable, and they underwent a protocol kidney biopsy at 3 months and at 2 years after transplantation. RESULTS: Histologic chronic allograft nephropathy was present in 25% of patients at 3 months and in 50% at 2 years, but was absent in the recipients of HLA-identical kidneys. Histologic worsening was associated with increased donor age, the presence of asymptomatic grade I acute rejection at 3 months, and an increased cyclosporine trough level. CONCLUSIONS: Protocol biopsies contribute important information that could be used to improve the prophylaxis of chronic allograft nephropathy.

Pregnancy in women with impaired renal function.

The outcome and consequences of pregnancy in women with impaired renal function are still debated. To assess the benefit of recent advances in coordinated obstetrical and nephrologic management, we analyzed fetal and maternal outcome of 43 pregnancies in 30 women with various types of primary renal disease and moderate to severe renal failure at conception defined by serum creatinine concentration (Scr) ranging from 0.11 to 0.49 mmol/l. All pregnancies took place during the 20-year period from 1975 through 1994 and were prospectively followed jointly by our Nephrology Unit and Obstetric and Neonatology Units of University Hospitals. Of the 43 pregnancies (45 fetuses), 13 ended in fetal death (including 5 first-trimester abortions and 8 fetal deaths beyond the 20th gestational week). There were 32 live births, a success rate of 82% not considering first-trimester abortions. Successful pregnancies were significantly more frequent in the last decade than in the preceding one (91 vs 65%, p = 0.05). Overall live birth rate was higher in pregnancies started with Scr < 0.20 mmol/l than in those with Scr > 0.20 mmol/l (80% vs 53%, p = 0.02). The upper preconception Scr value associated with a successful fetal outcome was 0.27 mmol/l. Hypertension was the major factor of fetal prognosis, as the relative risk of fetal loss was 10.6 times higher when hypertension was present at conception or early in pregnancy than when blood pressure was spontaneously normal or well-controlled by therapy. An accelerated course toward end-stage renal failure was observed in 7 patients (23%), all of whom had severe hypertension and heavy proteinuria at conception. We conclude that fetal outcome in patients with impaired renal function has been improved in recent years, due to advances in obstetrics and neonatology, improved blood pressure control and close co-operation between nephrologists and obstetricians, but that a risk of fetal loss and of accelerated deterioration of maternal renal disease still persists when Ccr at conception is lower than 25-30 ml/ min/1.73 m2.

Severe cutaneous hypersensitivity requiring permanent icodextrin withdrawal in a CAPD patient.

We report a case of severe cutaneous hypersensitivity to icodextrin occurring in a CAPD diabetic patient. Icodextrin withdrawal was necessary to achieve cutaneous recovery. Although rare, this adverse event should be kept in mind.

[The first Tunisian cardiovascular diseases register: processes and results]. / Le registre des maladies coronaires en Tunisie: organisation et premiers résultats.

BACKGROUND: In Tunisia, cardiovascular diseases are the leading causes of death (30%) and a few studies conducted in the population have demonstrated that the level of their risk factors is increasing. For policy makers, the health system impact of these diseases is currently a crucial issue. The National Public Health Institute has identified the implementation of a morbidity register as a priority. METHODS: A CVD morbidity register is implemented since 2001, in 3 different geographical populations having contrasted levels of health status (Tunis, Ariana and Ben Arous). The 3 regions are covering about 2 millions inhabitants which is the fifth of the overall Tunisian population. All coronary heart events occurring among adults 25 years old and above in the 3 populations are recorded. The diagnosis of events, case fatality and classification are defined according to MONICA criteria. The data are recorded from public and private hospitals, death certificates and autopsies. RESULTS: During the year 2001, the total number of myocardial infarction events was estimated at 942: in men, the age-standardized rates were 163.8/100000 in Tunis population vs. 161.9 in Ariana and 170.5 in Ben Arous. In women, the rates were respectively 43.4, 61.1 and 44.6. Medical causes of death registration was the most crucial problem in spite of the implementation of the death certificate designed according to WHO model. Specific surveys for clinical assessment and surveillance of risk factors were conducted in the register populations. CONCLUSION: It is the first time that data on coronary heart disease incidence and fatality are available in Tunisia through this experience which highlights the practical difficulties experienced in registering and coding coronary events in a developing country. The data source quality should be improved and the register should be integrated in the local health system.