Toll-like-Receptor Gene Polymorphisms in Tunisian Endemic Pemphigus Foliaceus.

Pemphigus foliaceus (PF) is considered to be caused by the combined effects of susceptibility genes and environmental triggers. The polymorphisms of Toll-like receptors (TLRs) genes have been associated with the risk of various autoimmune diseases. The aim of this study was to evaluate the potential association of TLR2-3-4 and 7 gene polymorphisms with Tunisian PF. Fourteen polymorphisms were analyzed in 93 Tunisian PF patients compared to 193 matched healthy controls: rs5743703-rs5743709 and (GT)n repeat (TLR2); rs5743305, rs3775294, and rs3775291 (TLR3), rs4986790 and rs4986791 (TLR4); and rs3853839 (TLR7). Our results showed that the genetic factors varied depending on the epidemiological feature stratification. In fact, in the whole population, no association with the susceptibility to PF was found. The TLR2 GT repeat seems to be closely associated with PF risk in patients originated from the endemic localities (group 3); the GT18 allele and the heterozygous genotype GT18/GT19 seem to confer risk to endemic PF (P = 0.02; OR = 2.3 [1.1-4.9] and P = 0.0002, OR = 20 [2.5-171], respectively). In contrast, the GT23 repeat could be considered as protector allele (P = 0.02, OR = 0.2 [0.06-0.87]). Furthermore, medium GT alleles which induce high promoter activity were also significantly more frequent in patients versus short or long GT repeats (P = 0.0018 with OR = 3.26 [1.5-7]). On the other hand, the TLR3-rs574305 AA genotype and A allele were significantly more frequent in patients whose age of the onset was above 35 years (group 2) (P = 0.038, OR = 1.78 and P = 0.009, OR = 3.92, respectively). Besides, the TLR4>rs3775294 A allele was found to be protector only in patients with sporadic features (groups 2 and 4) (P = 0.03, OR = 0.57 [0.3-0.9] and P = 0.006, OR = 0.24 [0.08-0.74], respectively). No statistically significant difference was observed in the genotypic and allelic frequencies of TLR-4 and TLR-7 gene polymorphisms. The present data suggest that TLR2and TLR3 polymorphisms are significantly associated with increased susceptibility to PF in the Tunisian population.

Involvement of the IL23/Th17 Pathway in the Pathogenesis of Tunisian Pemphigus Foliaceus.

Pemphigus foliaceus (PF) is a rare autoimmune skin disease caused by anti-Dsg1 pathogenic autoantibodies. It is considered as a Th2-mediated disease. Likewise, Th17 cells were recently described in the pathogenesis of the disease but their role is still unclear. We aimed to unravel the eventual implication of the IL23/Th17 pathway in the development of PF. A case-control study was conducted on 115 PF patients and 201 healthy controls using PCR-RFLP and AS-PCR methods. SNPs in IL23R, RORγt, IL17A, IL17F, IL17AR, TNFa, and STAT3 genes were genotyped. mRNA expression of IL23R and RORγt was evaluated using Q-PCR. The frequency of circulating Th17 cells was analyzed by flow cytometry. Genetic associations between IL23R>rs11209026, IL17A>rs3748067, IL17F>rs763780, and TNFa>rs1800629 and the susceptibility to PF were reported. Moreover, we revealed a significant increased frequency of circulating CD4+IL17+ cells as well as higher mRNA levels of RORγt and IL23R in PBMCs of patients. However, no significant increase of RORγt and IL23R mRNA expression was observed in lesional skin biopsies. In spite of the little size of specimens, our results provide converging arguments for the contribution of the IL23/Th17 pathway in the pathogenesis of PF.

Relevant genetic polymorphisms and kidney expression of Toll-like receptor (TLR)-5 and TLR-9 in lupus nephritis.

Toll-like receptor (TLR) genetic polymorphisms may modify their expression causing inflammatory disorders and influencing both susceptibility and severity of lupus erythematosus. We aim to determine whether TLR-5 and TLR-9 gene polymorphisms are implicated in the susceptibility to systemic lupus erythematosus (SLE) and lupus nephritis (LN) and to evaluate their expressions and distributions in renal LN patients' biopsies. The frequencies of two SNP in the TLR-9 gene and one in the TLR-5 gene was examined in 106 SLE patients (among them 37 LN patients) and in 200 matched controls by polymerase chain reaction-restriction fragment-length polymorphisms (PCR-RFLP) analysis. TLR-9 and TLR-5 expressions were assessed by reverse transcription (RT)-PCR and immunohistochemistry carried on LN renal biopsies compared to healthy renal tissue. A significant genotypic and allelic association was revealed between TLR-9-rs352140 and both SLE and LN (P < 0·05). The TLR-9 transcript level was significantly higher in LN biopsies compared to control (P < 0·05). This increase was observed histochemically in the tubulointerstitial compartment. TLR-9 was detectable in LN glomeruli patients but not in normal control glomeruli. No allelic nor genotype association was found with TLR-5-rs5744168 in SLE. but the T allele and the TT genotype were raised significantly in the LN group (P < 0·05). A significant increase in TLR-5 gene expression in LN biopsies, which contrasted with normal kidneys (P < 0·05), was confirmed by an intense and diffuse staining for TLR-5 only in LN tubules (P < 0·05). Our data show that TLR-5 and TLR-9 are susceptible genes to LN and that their expression is dysregulated in LN patients' kidneys, supporting a role of these mediators in the pathogenesis of LN.

[Adaptation and validation of the neurological soft sign's scale of Krebs et al. to children]. / Adaptation et validation d'une échelle des signes neurologiques mineurs chez l'enfant.

BACKGROUND: Neurological soft signs (NSS) include anomalies in motor integration, coordination, sensory integration and lateralization and could be endophenotypic markers in autism spectrum disorders (ASD). Their characterization provides a more precise phenotype of ASD and more homogeneous subtypes to facilitate clinical and genetic research. Few scales for NSS have been adapted and validated in children including children with ASD. Our objective was to perform an adaptation to the child of a scale assessing neurological soft signs and a validation study in both general and clinical populations. METHODS: We have selected the NSS scale of Krebs et al. (2000) already validated in adults. It encompasses 5 dimensions: motor coordination, motor integration, sensory integration, involuntary movement, laterality. After a preliminary study that examined 42 children, several changes have been made to the original version to adapt it to the child and to increase its feasibility, particularly in children with ASD. Then we conducted a validation study by assessing the psychometric properties of this scale in a population of 86 children including 26 children with ASD (DSM 5 Criteria) and 60 typically developing children. Children's ages ranged between 6 and 12 years, and patients and controls were matched for gender, age and intelligence. Patients were assessed using the Autism diagnostic Interview-revised and the Childhood Autism Rating Scale to confirm diagnosis. Typically developing children were assessed using the semi-structured Mini International Neuropsychiatric Interview for Children and Adolescents to eliminate any psychiatric disorder. All children with neurological pathologies (history of cerebral palsy, congenital anomaly of the central nervous system, epilepsy, tuberous sclerosis, neurofibromatosis, antecedent of severe head trauma) and obvious physical deformities or sensory deficits that could interfere with neurological assessment were excluded from the study. Both patients and controls were assessed using the Raven Progressive Matrices to exclude intellectual disability, and the adapted Krebs' scale for the assessment of NSS. RESULTS: Adaptation of the scale consisted of a modification in the order of items, in the use of concrete supports for the assessment of laterality and in the elimination of item constructive praxis. The internal consistency was good with a Cronbach alpha of 0.87. Inter-rater reliability was good, kappa coefficient was greater than 0.75 for 16 items, 3 items had a kappa value between 0.74 and 0.60, only 1 item had a kappa coefficient between 0.4 and 0.59. Good inter-rater reliability was also checked for the total score with a value of intra-class correlation coefficient (ICC) of 0.91. Principal component analysis found five factors accounting for 62.96 % of the total variance. About the comparison between patients and controls, significant differences were found for NSS total score (P=0.000) and all subscores. CONCLUSION: The adaptation for children of the Krebs et al.' NSS scale proved to be valid, especially in children with ASD.

CREM variant rs17583959 conferred susceptibility to T1D risk in the Tunisian families.

Type 1 diabetes mellitus (T1D) is a chronic autoimmune disease caused by the destruction of insulin-producing pancreatic ß-cells by autoreactive T cells. Studies in animal models, such as the non-obese diabetic (NOD) mouse reveal that this disease is under the control of several genes that encode molecules implicated in regulation of transcription factors and in T cell activation. In order to underline the role of the genes involved in this regulation pathways, we investigated, using the Sequenom MassARRAY platform, 13 single-nucleotide polymorphisms (SNPs) belonging to CREM, IRF5, STAT4, and STAT5a/b genes in 59 T1D Tunisian families. In the current study, we identified an association with rs17583959 (allele G; Z score=2.27; p=0.02; Genotype GG: score=1.96; p=0.04) of CREM gene. In LD analysis a strong LD between the 3 CREM variants (Block 1) was detected; rs2384352 was in complete LD with rs1148247. When haplotypes were constructed between CREM polymorphisms (rs1148247, rs17583959, rs2384352), AGA haplotype (H2) was significantly over-transmitted from parents to affected offspring (Z score=2.988; P=0.002) and may confer a risk for T1D disease. Whereas, AAG haplotype (H5) (Z score=-2.000; p=0.045) was less transmitted than expected to affected children suggesting its protective effect against T1D pathology. No significant association in IRF5, STAT4, and STAT5a/b genes were observed. In conclusion, this study shows an eventually involvement of CREM gene in the development of T1D pathology in Tunisian families. These facts are consistent with a major role for transcription factor genes involved in the immune pathways in the control of autoimmunity. Further researches of association and functional analysis across populations are needed to confirm these findings.

[Cigarette smoking initiation among Tunisian adolescents: Risk and protective factors]. / Les facteurs de risque et de protection de l'initiation à la cigarette chez les adolescents tunisiens.

BACKGROUND: Since smoking is a major public health problem among Tunisian teenagers, it is important to identify the underlying risk and protective factors associated with initiation of this behavior. METHODS: A cross-sectional, school-based survey of students was conducted by the Tunisian Ministry of Health among a nationally representative sample of 4172 adolescents aged between 12 and 20 years attending public, private, and professional secondary schools across Tunisia who participated in the Survey of the Health of Tunisian adolescents in 2000. For data analysis, we first calculated crude odds ratios (OR) followed by calculating adjusted OR after using multivariate logistic regression models. RESULTS: Almost one-third of respondents had already started smoking at an average age of 13 years, 6.4% among them smoked daily. Demographic vulnerabilities to smoking behavior were gender (boys more than girls), age and residence in urban areas and particularly in Greater Tunis and the North East. Familial and school factors were parental divorce, poor relationship with parents, poor integration into the peer group, and poor school investment. Psychological and behavioral factors were low self-esteem level and the occurrence of stressful life events, risk taking and alcohol consumption when there was no association with the depression, anxiety and body image. Protective factors against the experimental cigarettes were mainly sports and reading. CONCLUSION: There are many factors associated with smoking behavior among adolescents. All of these predictors need to be considered in smoking prevention among Tunisian teenagers.

MicroRNA-19a enhances proliferation of bronchial epithelial cells by targeting TGFßR2 gene in severe asthma.

BACKGROUND: Allergic asthma is characterized by inflammation and airway remodeling. Bronchial epithelium is considered a key player in coordinating airway wall remodeling. In mild asthma, the epithelium is damaged and fails to proliferate and to repair, whereas in severe asthma, the epithelium is highly proliferative and thicker. This may be due to different regulatory mechanisms. The purpose of our study was to determine the role of miRNAs in regulating proliferation of bronchial epithelial cells obtained from severe asthmatic subjects in comparison with cells obtained from mild asthmatics and healthy controls. METHODS: Human bronchial epithelial cells (BEC) were isolated by bronchoscopy from bronchial biopsies of healthy donors and patients with mild and severe asthma. MiRNA expression was evaluated using the TaqMan low-density arrays and qRT-PCR. Transfection studies of bronchial epithelial cells were performed to determine the target genes. Cell proliferation was evaluated by BrdU incorporation test. RESULTS: MiR-19a was upregulated in epithelia of severe asthmatic subjects compared with cells from mild asthmatics and healthy controls. Functional studies based on luciferase reporter and Western blot assays suggest that miR-19a enhances cell proliferation of BEC in severe asthma through targeting TGF-ß receptor 2 mRNA. Moreover, repressed expression of miR-19a increased SMAD3 phosphorylation through TGF-ß receptor 2 signaling and abrogated BEC proliferation. CONCLUSION: Our study uncovers a new regulatory pathway involving miR-19a that is critical to the severe phenotype of asthma and indicates that downregulating miR-19a expression could be explored as a potential new therapy to modulate epithelium repair in asthma.

[Thrombopenia and the nature of the microorganism in infected critically ill children]. / Thrombopénie et nature des germes infectants en réanimation pédiatrique.

BACKGROUND: Thrombopenia is correlated with sepsis and mortality in pediatric intensive care units. The purpose of this study was to find an association between thrombopenia and the microorganism type to guide the choice of empiric antibiotic therapy in infected critically ill children. MATERIALS AND METHODS: We conducted a prospective descriptive study, including all newborns, infants, and children admitted to a pediatric surgical intensive care unit from 1st January to 31st December 2009. We identified patients who developed an infection and/or thrombopenia (platelet count less than 100,000/mm(3)) during hospitalization. RESULTS: One hundred ninety-seven patients were included (57 newborns, 41 infants, 99 children). Ninety patients developed 100 infectious episodes during the study period. Of the 57 newborns enrolled in the study, 31 (54%) developed 37 infections. Seventy-six microorganisms (55 Gram-negative bacilli [GNB], 17 Gram-positive cocci, two Gram-negative cocci, two fungal pathogens) were identified during 65 infectious episodes in 55 patients. Thirty-four episodes of thrombopenia were observed in 30 patients. Thrombopenia was observed only in infected patients (P<0.001). Thrombopenia was associated with infections caused by GNB (26/28 vs 20/37, P=0.001) and by Klebsiella (16/28 vs 6/37, P=0.001) and may be associated with infections caused by GNB producing extended-spectrum beta-lactamases (P=0.07). Gram-positive cocci infections were correlated to the non-occurrence of thrombopenia (P=0.02). Postoperative peritonitis was also significantly associated with thrombopenia (P=0.03). The mortality rate in our patients was 12.7% (22.8% in neonates). There was an association between thrombopenia and death in univariate analysis (11/25 vs 19/172, P<0.001). Multivariate logistic regression analysis did not confirm thrombopenia as an independent predictive factor of mortality in children. CONCLUSION: Because of the relatively high proportion of resistant GNB, an empiric antibiotic therapy combining a carbapenem and an aminoglycoside may be indicated in infected critically ill children developing thrombopenia.

Psychometric properties of the Tunisian-Arabic version of the Women's Health Questionnaire.

OBJECTIVES: The Women's Health Questionnaire has been developed for the assessment of symptom perception in mid-aged women. It explores a range of psychological and physical symptoms and is one of the most used health-related quality of life measures. It was developed in the English language and is available in several other languages. The aim of this study was to evaluate the psychometric properties of the Tunisian-Arabic version of the questionnaire. METHODS: A Tunisian-Arabic translation of the original version of the Women's Health Questionnaire (36-item WHQ) was produced using the forward-backward translation method recommended by the designers. A total of 1231 women were anonymously recruited from the general population using the quota method of sampling. All women were administered the WHQ as part of a broader questionnaire; 1150 records were finally retained for analysis. Psychometric evaluation was performed for the original version of the WHQ (36 items) and then for the 23-item revised version proposed by the MAPI Research Institute. RESULTS: The acceptability and comprehensibility of the scale were good. The 36-item version showed overall good reliability, but some subscales lacked internal consistency. The validity was explored by principal component analysis and showed significant differences with the original English instrument and some deficiencies in its dimensional structure. The validity of the 23-item revised version was better. Finally, we suggest some adjustments to improve the reliability and validity of the instrument. CONCLUSION: The Tunisian-Arabic version of the WHQ is globally reliable and valid, but we recommend the use of an improved shortened version, more specific to mid-aged women.

[The tobacco cessation consultation of the Salah-Azeiz Tunis cancer center: one year results]. / La consultation d'aide au sevrage tabagique de l'institut de cancérologie Salah-Azeiz de Tunis : résultats à un an.

BACKGROUND: To reduce tobacco smoking is, in Tunisia, a public health priority. The tobacco cessation consultation is one of the interventions to fight against the tobacco epidemic; it is a new activity developed in the Salah-Azeiz Tunis cancer centre. The objective of this work is to evaluate the impact of the consultation on the smokers after one year of activities and to analyse the prognostic factors of tobacco cessation in order to improve the efficacy of such an activity in the future, in Tunisia. METHODS: The cessation methods were based on cognitive and behavioral therapies associated with nicotine patch, delivered free of charge. During one year (July 2003 to June 2004), 340 smokers were attended. Data on their smoking status and psychological characteristics were collected using a standardized questionnaire. RESULTS: The patients were mostly men (79%), these smokers did not present important anxiety-depressive troubles, 68% thought that they were able to quit easily. The majority (57%) smoked more than 20 cigarettes a day and was nicotine-dependent (Fagenström >7). Half of this population had already intended to stop, they declared to smoke mostly because of stress. The global cessation rate after a median follow-up of 32 weeks is 27%. The cessation rate lasting six months for 83 patients followed regularly was 23%. The good prognostic factors of cessation, after multivariate analysis, were (when taking out from the model the regular follow-up), to be confidant on the possibility to stop (OR=0.87 [0.78-0.97]). On the contrary, a high score (>7) for Fagerström test (OR=1.9 [1.1-3.4), the use of smoking to fight against stress (OR=1.08 [1.0-1.2) and a smoking environment at home (OR=4.5 [1.1-18.9]) were prognostic of a failure in quitting smoking. CONCLUSION: These results show that the cessation rate, which is still too low as compared with the literature, could be increased by a better follow-up of smokers associated with an information campaign on the existing possibilities to quit smoking in Tunisia.

Pancreatic autoantibodies in Tunisian children with newly diagnosed type 1 diabetes.

We analyzed 86 children with newly diagnosed type 1 diabetes for antibodies to islet cells (ICA), glutamic acid decarboxylase (GADA), second-islet antigen (IA-2A), and insulin (IAA) in order to evaluate the prevalence of immune-mediated type 1 diabetes, as well as to recognize which autoantibody combination is more frequently associated with the disease. A positive result for one or more diabetes-related antibodies evaluated was found in 78 children (90.7%). With regard to single autoantibody testing, ICA were found to be positive in 49 patients (57%), GADA in 56 (65.1%), IA-2A in 37 (43%), and IAA in 43 (50%) patients. Combining the determination of at least two autoantibodies, GADA and/or IAA were better detectable than other antibody combination, being positive in 70 patients (81.4%). GADA and IA-2A represent also a useful screening combination; being positive in 65 patients (75.6%). Our data indicate that the vast majority of cases of type 1 diabetes in children may be considered as immune-mediated and that multiple autoantibody analysis improves identification of the disease.

[Breast cancer prognosis in Salah Azaiez Institute of Cancer, Tunis]. / Pronostic du cancer du sein à l'Institut de Carcinologie Salah Azaïez de Tunis.

We estimated survival rate at 9 years of all (470) women with breast cancer diagnosed at Salah Azaïez Institute of Cancer in Tunis to identify the main prognosis factors. Data were collected on residence, socioeconomic level, circumstances of discovery of the tumour, histological type, tumour size, presence of metastases, extension of the tumour, treatment and survival. Comparison of survival curves was done with Log Rank test. Cox model was used for multivariate adjustments and calculation of the hazard ratio (HR) (relative risk of death). There was a survival rate of 61% at 5 years and of 51% at 9 years. Tumour size >5 cm was significantly associated with lower survival as was capsular rupture. After stratification for tumour size and age, only surgery and radiotherapy were significantly associated with improved survival.

[Health transition in Tunisia over the past 50 years]. / La transition sanitaire en Tunisie au cours des 50 dernières années.

We describe the dramatic demographic, socioeconomic and health changes witnessed in Tunisia over the past 50 years. Demographically, the gross mortality rate and the infant mortality rate have gone from 19 per 1000 and 150 per 1000 respectively in 1956 to 5.7 per 1000 and 26.2 per 1000 now, and life expectancy at birth going from 50 to 72 years for the same period. Socioeconomically, the urban population has risen from 25% to 62%, the literacy rate from 15% to 73%, and the per capita income has increased 5-fold in real terms. Epidemiologically, the infectious and perinatal diseases prevailing in the 1960s have decreased whereas chronic and degenerative diseases have risen. The proportion of the GNP related to health expenditure has risen from 3.8% to 6.2%. The implication of these changes on the Tunisian health system and the need to adapt in terms of curative care and prevention of risks are discussed.

[Life years lost and epidemiological transition in the Sfax region (Tunisia)]. / Années de vie perdues et transition épidémiologique dans le gouvernorat de Sfax (Tunisie).

OBJECTIVE: To assess the burden of disease in the Sfax region and identify the main diseases that are the cause of lost life years due to premature death. METHODOLOGY: The calculation of lost life years due to premature death was conducted using the demographic mortality data for the region obtained from the National Institute of Statistics combined with data on the classification of the causes of death collected through a survey on these causes conducted through a random sample taken from half of the deaths in the region. As described by Murray and Lopez, years of life lost as a result of premature death represent the difference between the age of death and an age corresponding to life expectancy falling between 65 and 85 years. RESULTS: Out of a total of 52,316 life years lost that were recorded 27,902 were in the male population and 24,414 in the female. The main diseases found in males which cause lost life years are accidents (24.9%), cardiovascular diseases (17.3%), communicable diseases (17%), respiratory diseases (10.8%), prenatal problems (59.5%), and cancer (7.5%). For women the main causes were cardiovascular diseases (26.5%), respiratory illness (15.5%), accidents (11.5%), communicable diseases (10.3%) and cancer (9.5%). RECOMMENDATIONS: These results marking the epidemiological transition in the region should serve to steer decision-makers to better rationalize and plan for health care costs and expenditure.

[Knowledge, attitudes and behaviours of women towards breast cancer screening]. / Connaissances, attitudes et comportements des femmes vis-à-vis du dépistage du cancer du sein.

The objective of this study was to describe knowledge, attitudes and behaviour of women towards breast cancer screening methods in two regions of north Tunisia. Thus 936 women from Ariana (urban region) and 993 women from Zaghouan (rural region) were selected and answered a questionnaire on their perception of the gravity of breast cancer, the vulnerability of women, the efficacy of screening and their use of screening. The use of screening was significantly more frequent in Ariana for both clinical breast examination and mammography, but screening use was modest. This low use of breast cancer screening contrasts with a positive attitude to breast cancer screening methods. The factors positively associated with use of screening were urban residence, age between 35 and 49 years, educational level and the perception that cancer treatment had advanced in Tunisia.

[Knowledge and practice of doctors and midwives working in primary health care regarding screening for cervical and breast cancers]. / Connaissances et participation des médecins et sages-femmes de première ligne vis-à-vis du dépistage des cancers du col utérin et du sein.

We assessed the knowledge and practices of breast and cervical cancer of 286 physicians and 126 midwives working in primary health care in Tunis who responded to an anonymous questionnaire. Questions were related to knowledge of the epidemiology and survival rates in the early stages of breast and cervical cancers, to training in this domain and to the degree of involvement in this screening. The knowledge of the two cancers was relatively modest among both physicians and midwives. The systematic practice of Pap smear was significantly more frequent among midwives than physicians. The same result was observed for systematic clinical breast examination. Lack of training about carrying out Pap smears and the large number of consultations were the main factors negatively associated with systematic Pap smear and clinical breast examination practice.

[Smoking dependence and symptoms of anxiety and depression among Tunisian smokers]. / Dépendance tabagique et troubles anxio-dépressifs chez le fumeur tunisien.

INTRODUCTION: The aim of this study was to describe the incidence of depression and anxiety, and their relationship with smoking dependence, in patients attending a Tunisian smoking cessation clinic. METHODS: We studied 72 Tunisian smokers attending the smoking-cessation clinic at the Charle Nicolle Hospital in Tunis. Nicotine dependence was assessed by the Fageström Test for Nicotine Dependence. Anxiety and depression symptoms were measured using the HAD (Hospital Anxiety Depression) Scale. RESULTS: The prevalence of anxiety and depression was 22.9% (16 patients) and 20% (14 patients) respectively with four patients (7.1%) exhibiting symptoms of both. Overall, 50% of the group had emotional morbidity with high HAD scores for depression or anxiety, or both. Smokers with symptoms of anxiety and/or depression had higher physical and psychological dependence, smoked more at times of stress, had a reduced quitting rate and endured more withdrawal symptoms than those smokers without anxiety or depression. CONCLUSIONS: The data of this survey from Tunisia, a country that has just put in place a tobacco control strategy, underline the high rates of anxiety and depression that exist in patients attending a smoking cessation clinic. It confirms the association between anxio-depressive disorders and a high level of smoking dependence.

[Anxiety and depressive disorders in tobacco dependence]. / Troubles anxieux et dépressifs dans la dépendance tabagique.

The association between tobacco dependence and various forms of anxiety and depressive disorders is well established. The presence of these disorders constitutes a key cause of failure in subjects seeking to stop smoking. In addition to the clinically manifest forms of such anomalies, systematic screening for minor forms of these disorders was performed at the Centre for Tobacco Studies of Créteil, France; as well as the standard questionnaire concerning personal and familial history and current psychological well-being, subjects were asked to complete two self-questionnaires, the HAD (Hospital Anxiety Depression score) and the BDI (Beck Depression Inventory, abridged version) together with the MINI (structured mini-interview). In a series of 400 heavy smokers, sub-syndromes of such anxiety and depressive disorders were noted in 34% of subjects, and a combination of anxiety and depressive disorders was seen in 2/3 of these subjects, mainly general anxiety and social phobia, which were frequently preceded by depressive episodes. In these forms of tobacco dependence with anxiety and depressive disorder, relapse was very common in spite of nicotine substitution therapy (NST), usually as a result of a depressive episode that tended to subside very rapidly on resumption of cigarette smoking. Psychotropic therapy involving selective serotonin reuptake inhibitors (SSRIs) coupled with NST resulted in lasting success accompanied by an often unexpected and spectacular improvement in psychological status. These findings confirm the role of mood disorders in tobacco addiction in keeping with other types of addiction.

[Nicotine substitution therapy: 10 years later]. / Le traitement de substitution nicotinique dix ans après.

To be efficient, nicotine substitution therapy (NST) must be part of a global strategy comprising several stages. The first consists in evaluating and re-enforcing motivation, since smoking cessation is impossible unless the patient is clearly motivated. The second stage is the withdrawal period that lasts for several days or months. NST is the first medicinal treatment that has demonstrated its efficacy in controlled studies: it reduces the withdrawal syndrome and doubles the chances of success at the end of the standard 3-month treatment. Recent studies have shown that the results can be improved: by adapting the dose to the degree of dependency and by using higher doses and/or associating two types of nicotine substitutes; by prolonging NST for as long as the withdrawal syndrome persists; by treating the anxiety and depression, often present in heavy smokers. The third stage is aimed at avoiding relapses, by ensuring prolonged follow-up and treating the various possible causes: eating disorders and weight gain, acute or chronic stress, depression, environment.... At all the stages of care, behavioural and cognitive therapy enhances the chances of success.

[Depression, tobacco dependence and nicotine]. / Dépression, dépendance tabagique et nicotine.

The purpose of the study was to illustrate, through an observation, the association between depression and smoking dependence, as well as the considered anti-depressive properties of nicotine. Fageström Test for Nicotine Dependence was confirmed by the urinary cotinine dosage, and the expired Carbon Monoxide assessed the nicotine dependence. The anxio-depressive co-morbidity was determined through the cross-examination associated to the HAD test (Hospital Anxiety Depression Scale); then, in case of anomaly, by the depression inventory of Beck (13 items) and the structured interview: the Mini International Neuro Psychiatric Interview (MINI). Our patient, born in 1938, with the personal history of manic-depressive psychosis and alcoholic dependence severed in 1987, came to consult in 1995, after several smoking cessation attempts, followed every time by an extended and severe depression. He smoked 40 cigarettes per day, with a very high dependence (score of Fagerström = 10). The HAD and the Beck tests being normals; smoking cessation program has begun with nicotine patches. At the end of three months, he fell in a severe and resistant depression that continued during 2 years. Then, he stopped completely smoking. In 1997, a progressive treatment by nicotine-gum (NG) was proposed. Since the second week, while taking 2 to 3 NG per day, and without having modified his ADT, his psychological state improved, and in 3 months he recovered his previous psychological form. Confronted to literature data, this observation underlines the association between anxio-depressive states and the high level of smoking dependence. In the same way, the improving psychological effects of nicotine replacement, confirms the nicotine anti-depressive properties.