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Initial medical certificate is a descriptive medical and legal document whose purpose is to prove the existence of a damage and to enable the victim to access his or her right. The purpose of our study was to study the content and to evaluate the writing quality of initial medical certificates. We conducted a retrospective and descriptive study over an 18-month period, from January 2017 to June 2018. We collected data from 450 initial medical certificates at the Forensic Medicine Department of the Charles Nicolle University Hospital in Tunis. The quality of the initial medical certificates was assessed using a template that allowed to assign them a score out of 30. A mean score was mainly assigned to initial medical certificates Template scores ranged between 9.5 and 27.5/30 with an mean of 18.59/30. General practitioners and specialist physicians, such as ophthalmologists, neurosurgeons and doctors using the support provided by the Ministry of Health wrote better certificates. Similarly, we noted better quality of writing when certificates dealt with intentional assaults and injuries. Our study shows that the majority of initial medical certificates does not conform to editorial guidelines. These shortcomings are probably related to the fact that doctors have never received adequate medical-legal training.

Infliximab (IFX) is a chimeric monoclonal antibody which has proven its efficacy in the treatment of inflammatory diseases. However, its efficacy can be limited by the development of anti-IFX antibodies (ATI) resulting in a therapeutic failure of IFX. ATI plasmatic monitoring is then indicated to optimize IFX treatment. The aim of this study was to validate an ELISA (enzyme linked immuno sorbent assay) method of ATI plasmatic monitoring. Methods Assessment of performance was based on the study of correlation and concordance (Bland Altman method) of the absorbances measured by the two readers. ELISA kit validation was made by calculating the accuracy and the exactitude. Results We collected 23 samples. Their mean age was 46 years and sex ratio M/W was 0.92. In nine cases, plasmatic AIT were positive and in 14 cases, they were not detected. Correlation between the two readers showed a correlation coefficient r2 of 99.95%. Concordance limits of the confidence interval 95% were [-112.768%-41.425%] with a bias of -35.671%. Repeatability and reproductibility were checked by a positive control and coefficients of variation were respectively of 5.574% and 14.184%. Limits of detection and quantification were respectively of 0.046 and 0.086. The positive predictive value was 0.5 and the negative predictive value was 1. The sensitivity was 100% and the specificity was 83%. Conclusion The assessment of the performance of the tested microplate reader and the validation of the tested ELISA kit showed good results allowing ATI routine measurement to optimize therapeutic management of patients treated by IFX.

Epithelial-mesenchymal transition (EMT) is a process by which differentiated epithelial cells undergo a phenotypic conversion and acquire a mesenchymal phenotype, including elongated morphology, enhanced migratory and invasion capacity, and greatly increased production of extracellular matrix (ECM) components. This phenomenon plays a pivotal role in embryonic development, wound healing and tissue regeneration. It has also been involved in organ fibrosis. Some studies suggest that following injury, renal tubular epithelial cells undergo reprograming in mesenchymal cells, and thus constitute an important source of de novo myofibroblasts invading the renal interstitium and contributing to fibrosis. However, an increasing number of studies raise doubts about the existence of this process in vivo. The role of EMT in the development of renal fibrosis remains a matter of intense debate and may depend on the model studied. In this review, we describe the role of EMT in the development of fibrosis of renal graft, and then we propose approaches for detecting and treating renal fibrogenesis by targeting TEM.

Evaluate the anti-erythrocyte and anti-HLA immunization rates in hemoglobinopathies.Cross-sectional study (October 2009-March 2010) on 83 patients followed for hemoglobinopathies. The irregular antibodies research is realized by two techniques: indirect Coombs and enzymatic technique on gel cards. The search for anti-HLA class I antibodies is done by complement dependent lymphocytotoxicity.The mean age was 30 years (14-64 years), the sex ratio M/F is 0.84. Our series included 42 cases of sickle cell disease (29 homozygous sickle cell anemia and 13 sickle-thalassemia) and 41 cases of thalassemia syndromes (26 major and 15 intermediate). The anti-erythrocyte alloimmunization rate is 10.84% without difference between thalassemia syndromes and sickle cell disease. The autoimmunization rate (22.89%) is higher in thalassemia syndromes (41.46%) than in the sickle cell disease (7.14%) (P0.001). The anti-HLA immunization rate is 31.6% without difference between thalassemia syndromes and sickle cell disease. The young age, transfusion at a young age and the total number of transfusions are the factors that increase the risk of anti-erythrocyte autoimmunization. No clinicobiological parameter does influence the anti-erythrocyte and anti-HLA alloimmunization. There is no significant association between anti-erythrocyte and anti-HLA immunization.The erythrocyte and anti-HLA anti-immunization rates are high in our series. Preventive strategy is needed to ensure optimal blood safety.

The IgA nephropathy (IgA-N) is considered the most common form of primary glomerulonephritis and its pathogenic mechanisms are very complex. The study of several genes which encode for immunoregulator molecules in inflammatory and immunological responses during the disease, allowed to describe some number of polymorphisms would be involved in the molecular expression, the road marking, the synthesis and\or the binding to the receptors. So an abnormality of the molecular function associated with its polymorphism would be suggested in the genetic predisposition to the disease.To determine interleukin 1 (IL1), interleukin1 receptor antagonist (IL1 Ra), CTLA-4 and Apo1/Fas genes polymorphisms frequencies in IgA-N in order to estimate the impact of these polymorphisms in the disease susceptibility.The polymorphism of a single nucleotide (SNP) at (-889) IL1 a of 21 IgA-N patients and 100 healthy blood donors, as controls, was studied by PCRSSP. The SNPs of the IL1 ß (+3954), CTLA-4 (+49) and l'Apo1/Fas were analyzed by PCR RFLP and finally the polymorphism of the IL1 Ra gene was determined by a PCR VNTR (variable number tandem repeat).Investigation of IL1a/ß and Apo1/Fas polymorphisms showed no differences in genotypes and alleles frequencies between IgA-N patients and controls. However, genotype AA of CTLA-4 exon1 (+49) was significantly higher in patients (47.62%) than in controls (9.1%) p0.001. Nevertheless, the clinical, histological and biological characteristics of IgA-N were similar in AA CTLA-4 genotype patients compared to AG or GG genotype patients. We fund also, a significant increased frequency of 1/1 IL1 Ra genotype in IgA-N patients (95.24%) compared to controls (54%) (p0.001) (p0.001).We conclude that the susceptibility to IgA-N seems to be associated with the presence of CTLA-4 AA and IL1 Ra 1/1 genotypes in Tunisian population. However, the lack of association between IL1 a/ß and Apo1/fas genes polymorphisms should be further investigated by large population based studies.

Antiphospholipid syndrome is revealed by Budd Chiari syndrome in 5% of the cases. Antiphospholipid syndrome is characterized by venous or arterial thrombosis, foetal loss and positivity of antiphospholipid antibodies, namely lupus anticoagulant, anticardiolipin antibodies and anti-beta2-glycoprotein I. Anticardiolipin antibodies was reported in auto-immune thyroid disorders, particularly in Grave's disease. Antiphospholipid syndrome associated to Grave's disease was reported in only three cases.To describe a case report of association of Grave's disease and antiphospholipid syndrome.We report the first case of Grave's disease associated with antiphospholipid syndrome, revealed by Budd Chiari syndrome.Our observation is particular by the fact that it is about a patient presenting a Grave's disease associated with antiphospholipid syndrome revealed by Budd Chiari syndrome. This triple association has never been reported in literature. Although association between antiphospholipid syndrome and Grave's disease was previously described, further studies evaluating the coexistence of these two affections in the same patient would be useful.

Hepatitis C viral (HCV) infection has been shown to lead to auto-immune phenomena.We review the prevalence of serological auto-immune disorders associated to HCV infection and to clarify their clinical significance.Literature review.The serological immune response to HCV infection may include the development of cryoglobulinemia, rheumatoid factor, anticardiolipin, antinuclear, anti-liver-kidney-microsome 1 and anti-smooth muscle antibodies. Serological auto-immune manifestations were explained by the lymphotropism of HCV and the polyclonal activation of B cells. Interferon-based treatment of HCV infection may precipitate or exacerbate the associated auto-immune disease.In patients with serological auto-immune disorders associated with HCV infection, a very careful analysis of clinical and biological features is needed. Application of classification criteria of systemic auto-immune diseases and testing more specific antibodies can resolve this point.

Chronic viral hepatitis C is often associated with various autoimmune disorders. We report two patients infected by genotype 1b hepatitis C virus associated with primary biliary cirrhosis. These patients had anicteric cholestasis associated with cytolysis and positivity of M2 antimitochondrial antibodies at a titre of 1/200. Liver biopsy revealed chronic hepatitis in one case and histological pattern of primary biliary cirrhosis in the other. One patient was treated by antiviral therapy; the other only by ursodesoxycholic acid because of the association with hemolytic anemia. Association between primary biliary cirrhosis and chronic viral hepatitis C is uncommon and associated with diagnostic and therapeutic challenges.

Reports of an association between epilepsy and coeliac disease (CD) are not new. Chapmann reported a prevalence of epilepsy in CD of 5.5% and accepted a figure of 0.5% for the community. Prevalence of coeliac disease among epileptic patients is not well established. The aim of this study is to determine the prevalence of CD in epileptic patients for this 49 epileptic patients (31 male and 28 female) were selected between January 96 et June 99 to underwent fibroscopy with intestinal biopsy. Anti body to gluten were measured in most patients. The patients with villous atrophy underwent cranial computed tomography. 4 of 49 patients (8.1%) were identified as having coeliac disease on the basis of a flat intestinal mucosa with increasing of LIE. 2 among this 4 patients had recurrent diarrhea. Any patient showed cerebral calcification associated with epilepsy and CD. Only one patient among 4, followed a gluten free-diet with a significant reduction in seizure frequency. This suggest that CD should be ruled out in all case of epilepsy of unexplained origin.

Congenital heart block (CHB) associated with maternal anti-SSA/SSB antibodies: a report of four cases. CHB detected in utero is strongly associated with maternal antibodies to SSA (Ro) and SSB (La). Their pathogenic role in the development of CHB has been established in several studies. The mothers of affected infants frequently had autoimmune disease (systemic lupus erythematosus, Sjögren's syndrome) or were entirely asymptomatic. It is very difficult to identify pregnant asymptomatic mothers carrying anti-SSA/SSB antibodies. We report four cases of infants born to asymptomatic mothers with anti-SSA/SSB antibodies, three of them developed isolated congenital cardiac heart block and one with no evidence of CHB. All three CHB are detected during pregnancy between 16 and 24 weeks of gestation. All maternal sera contained antibodies to SSA alone or the both SSA and SSB. Three of four subsequent pregnancies were complicated by heart block. One child affected died in utero. While the two other newborns with CHB required pacemaker insertion during the first 3 months of life. Although the association of anti-SSA/SSB with CHB is widely accepted, the precise mechanism by which these antibodies cause cardiac conduction abnormalities remains to be defined. Antibodies to SSA/SSB have been proposed to be a serologic marker for neonatal lupus syndrome and CHB. Fetal and neonatal diseases are presumed to be due to the transplacental passage of these IgG autoantibodies from the mother into the fetal circulation. Since these antibodies may have a pathogenic role in CHB, screening of infants with isolated CHB or neonatal lupus and their mothers for the presence of anti-SSA and anti-SSB is strongly recommended.

Cryoglobulins are immunoglobulins which reversibly precipitate at cold temperatures. They are usually accompanied with polymorphic clinical manifestations and biological abnormalities. Cryoglobulins are associated with various clinical disorders which include autoimmune diseases, lymphoproliferative and infectious disorders. Because of their low concentration, detection and quantitation of cryoglobulins need very rigorous conditions when collecting blood from patients.

Immunoblotting and ELISA methods are now employed for the detection of anti Ro/SSA and anti La/SSB antibodies sometimes more often than double immunodiffusion or counter-immunoelectrophoresis. We have developed an immunoblotting technique for the detection of anti Ro/SSA and anti-La/SSB antibodies. This assay named IB-Hela, which uses a Hela cell extract, was compared with the double immunodiffusion technique like two other commercial immunoassays (Elisa test from Sanofi-diagnostic Pasteur and Line immunoassay from Innogenetics). This evaluation shows a good agreement especially in the case of Ro/SSA antibodies detection. IB-Hela seems to be useful in the La/SSB detection with a better sensitivity than the double immunodiffusion technique. We conclude that the IB Hela is helpful for the search for anti-Ro/SSA and anti-La/SSB autoantibodies and that it can be used as an alternative method to the classical techniques of immunodiffusion and counter immunoelectrophoresis.

We report the case of a young Tunisian woman hospitalised for reasons of general ill health. A immunological check-up revealed autoimmune disturbances and in particular anti-ribosomal P antibodies. We discuss the possible relation of these antibodies to the hepatitis C infection from which the patient was also suffering.

We searched for antibodies to hepatitis C in a sample of 3079 Tunisians in the suburban area of Tunis. 30 people were positive by ELISA and 22 were confirmed by immunoblotting. This result represents a prevalence of 0.71% which is close to the values reported in European countries of the Mediterranean area.

Antiphospholipids antibodies (AAP) were investigated in plasma of 62 patients with systemic lupus erythematosus, and studied for the possible interference of the excess in factor VIIIc-Von Willebrand factor (VWF-VIIIc) complex in the detection of lupus anticoagulants (LA) by the activated partial thromboplastin time (APTT). We used four commercial reagents and noted that each one exhibited a different level of sensitivity of LA; the most sensitive one allowed the detection of 16 LA positive plasmas while the less sensitive reagent detected only 6 positives. The Elisa test for IgG and IgM AAP detection was positive in 25 out of 62 plasmas (40%). Comparison of the Von Willebrand factor antigen level and the APTT values showed a significant negative corrélation with 2 reagents (r = 0.369, p0.01 and r = 0.272, p0.05 respectively) that were also the less sensitive to LA. The interference of an excess in VWF-VIIIc complex was further studied by the addition of purified factor VIII in 3 LA positive plasmas. Our results suggests that an excess of factor VIIIc could lead to false negative LA, using certain APTT reagents. We conclude that a more accurate LA detection require: sensitive reagents, a pool of normal plasmas selected with normal factor VIII level, as well as repeated testing of blood sampling withdrawn away of an inflammatory process to avoid false negative LA detection.

Antiphospholipids antibodies (AAP) were investigated in plasma of 62 patients with systemic lupus erythematosus, and studied for the possible interference of the excess in factor VIIIc-Von Willebrand factor (VWF-VIIIc) complex in the detection of lupus anticoagulants (LA) by the activated partial thromboplastin time (APTT). We used four commercial reagents and noted that each one exhibited a different level of sensitivity of LA; the most sensitive one allowed the detection of 16 LA positive plasmas while the less sensitive reagent detected only 6 positives. The Elisa test for IgG and IgM AAP detection was positive in 25 out of 62 plasmas (40%). Comparison of the Von Willebrand factor antigen level and the APTT values showed a significant negative corrélation with 2 reagents (r = 0.369, p \textless 0.01 and r = 0.272, p \textless 0.05 respectively) that were also the less sensitive to LA. The interference of an excess in VWF-VIIIc complex was further studied by the addition of purified factor VIII in 3 LA positive plasmas. Our results suggests that an excess of factor VIIIc could lead to false negative LA, using certain APTT reagents. We conclude that a more accurate LA detection require: sensitive reagents, a pool of normal plasmas selected with normal factor VIII level, as well as repeated testing of blood sampling withdrawn away of an inflammatory process to avoid false negative LA detection.

The anticardiolipin antibodies (aCL) are acquired inhibiting antibodies of the coagulation process. They interfere with the anionic phospholipids of the cellular membranous. These are frequently associated to the autoimmune diseases, especially the systemic lupus erythematosus (SLE), they expose the patient to thrombotic complications. In order to define the possible and prognostic predictive value of these aCL, a sequential research of these antibodies was performed on 12 patients suffering from SLE since 2 to 11 years. An average of one sample per year was drawn, either during an attack or in a routine control check. The detection of these IgG aCL did not appear to be related with be course of the disease. In fact, 3 of our patients, ill since respectively 2, 7 and 11 years, never showed any aCL. These aCL were positive during an attack in 80% of the cases. This positivity was associated to vascular thrombosis (2 cases), and cutaneous vascularity (6 cases) and, in one case, the presence of aCL was linked to inutero fetal death due to retruplacentary hematoma. This study confirms the association between aCL and thrombosis during systemic lupus erythematosus.

In this study, we have analyzed the clinical and serological features related to 16 Tunisian children in whom diagnosis of systemic lupus erythematosus was made before or at the age of 15. Renal involvement was found in 75% of cases and renal biopsies have mostly revealed severe histologic patterns. All of the patients who have been followed received corticosteroids and in some cases required additional cytotoxic drugs in order to control disease activity. Five children died in a context of a renal failure. This study of childhood lupus in Tunisia confirms that the clinical course of this disease in children is often aggressive.

The evolution of immunological parameters in mediterranean visceral leishmaniasis reveal a type III mixed cryoglobulin with rhumatoid factor activity and antileishmania antibodies. This cryoglobulin follows the clinical signs of the disease and disappear under treatment. The authors insist on the transitory character of this cryoglobulin which is in relation with polyclonal stimulation of the immune system by parasitical infection.