[Sudden cardiovascular death in adults: Study of 361 autopsy cases]. / La mort subite cardiovasculaire de l'adulte : étude autopsique de 361 cas.

AIMS OF THE STUDY: To describe epidemiological aspects of sudden cardiovascular death and to specify the etiopathogenic characteristics. PATIENTS AND METHOD: Our study is retrospective and descriptive. It included 361 cases of sudden cardiovascular death, which underwent autopsy in forensic medicine department of Monastir during eight years, from 1st January 2004 to 31st December 2011. RESULTS: The incidence of sudden cardiovascular death was 9 per 100,000 person. A marked male predominance was noted. The mean age was 55.75 years. In our series, myocardial infarction represents the leading cause of sudden cardiovascular death, 57.8% of cases. Other etiologies were hypertrophic cardiomyopathy (4.7%), heart failure (1.9%), arrhythmogenic right ventricular dysplasia (2.8%), valvular disease (2%), cardio-myo-pericarditis (1.9%), hydatid cyst of the heart (0.8%), ruptured aneurysm (2.5%), pulmonary embolism (1.9%) and aortic dissection (1.3%). A sudden cardiovascular death at work was found in 25 cases. These cases pose essentially a problem of imputability. CONCLUSION: Sudden cardiac death is usually the complication of underlying heart disease, sometimes overlooked. Several risk factors are involved. Sudden cardiac death in healthy heart or death caused by arrhythmia is an important entity seeking the intervention of several actors (forensic doctor, cardiologist, geneticist, media…) for prevention.

[Arrhythomgenic right ventricular dysplasia and sudden death: An autopsy and histological study]. / Dysplasie arythmogène du ventricule droit et mort subite : étude autopsique et histologique.

Arrhythmogenic right ventricular dysplasia (ARVD) is cardiomyopathy where normal myocardial tissue is replaced with fibrofatty tissue. Histological examination performed on myocardial biopsy or on autopsy samples are used to confirm the diagnosis. However, in many cases, the diagnosis cannot be made on a simple macroscopic and histological study and requires genetic analysis and molecular biology. In this work, we propose to describe the main macroscopic and histological findings of ARVD through the study of an autopsy series. We report 12 autopsy cases of sudden death in ARVD collected in the Department of Forensic Medicine of the University Hospital Fattouma Bourguiba Monastir (Tunisia) during a period of 20years. Microscopic examination was performed on 5microns thick histological sections. All slides were reviewed by two operators in a double blind (physician pathologist, pathologist) and in each, the percentage of adipose tissue, fibrosis and infarction in the right ventricle, left ventricle and interventricular septum, the presence or absence of inflammatory infiltrate, the presence or absence of signs of degeneration of myocytes were noticed. ARVD was found in 12 cases (1.8% of sudden cardiac death). The age ranged between 13 and 67years (mean age: 45.3years). The death occurred in half of the cases during exercise. Macroscopic examination of the RV showed the presence of a wall thinning (thickness<3mm) in 9 cases. Histological study highlight RV adipose infiltration in all cases with a percentage between 15% and 60%, fibrotic lesions were observed in only 9 cases with an average percentage of 10.25% and signs of degeneration of myocytes were noted in 10 cases. In concordance with what has been reported in the literature, there is still no consensus regarding the criteria to be adopted to pose with certainty the diagnosis of ARVD and the presence of adipose tissue remains the criterion more suggestive.

[Cardiac troponin I and the post-mortem diagnosis of myocardial damage]. / Intérêt du dosage post-mortem des troponines I cardiaques dans l'identification des lésions myocardiques.

UNLABELLED: The aim of this study is to analyse the diagnostic efficacy of post-mortem dosage of cardiac troponine I in cadaver fluids in detection of myocardial damage. MATERIAL AND METHODS: Our study is prospective, interesting 72 corps autopsied at the Department of Forensic Medicine of the University Hospital Fattouma Bourguiba of Monastir-Tunisia. Were excluded from the study, resuscitated cases and those examined more than 48h after death. Levels of cardiac troponine I were measured in pericardial fluid, cardiac blood and peripheral blood. Statically significant correlations between different variables levels of cardiac troponine I and cardiac damage were studied. Receiver-operator characteristic (ROC) curves were generated and areas under the curves were determined. SPSS (version 12.0) et MedCalc statistical software (version 11.0) were used for statistical analysis. Results were considered to be statistically significant when P<0.05. MAIN RESULTS: Cardiac troponin I levels in pericardial fluid, cardiac and peripheral blood are correlated significantly between subject with and without observable signs of myocardial damage with a P value respectively at 0.0007, 0.0009 and 0.004. ROC curves analysis showed that the pericardial fluid have the best sensibility and specificity with a cut-off level at 108ng/ml and an area under the curve at 0.925. CONCLUSION: Our data indicate that cardiac troponin I may be a powerful aid in the diagnosis of myocardial damages. This biological test can be used in triaging sudden deaths before to external examination versus complete autopsy.

[Severe microbial keratitis: report of 100 cases]. / Les abcès graves de la cornée: à propos de 100 cas.

PURPOSE: To study predisposing factors, clinical aspects, and microbiological diagnosis in severe microbial keratitis, and to discuss the therapy and visual outcome. MATERIAL: and methods: A prospective and retrospective study concerning patients presenting microbial keratitis hospitalized in department B of the Hedi Raies Ophthalmology Institute (Tunis, Tunisia), from August 1996 to November 2004. RESULTS: One hundred patients with microbial keratitis were hospitalized (45 females and 55 males; ranging in age from 11 to 87 years). The principal predisposing factors were ocular surface pathology (30%), ocular trauma (28%), prior ocular surgery (17%), and contact lens wear (8%). The corneal scraping culture was positive in 42% of cases, isolating Gram-positive bacteria (48.6%), Gram-negative bacteria (29.7%), and fungi (21.6%). The majority of our patients (93%) had broad-spectrum topical antibiotics with therapeutic success in 53.8% of cases. Systemic antifungal agents were indicated in 17 cases. Surgery was necessary in 25.8% of cases: therapeutic keratoplasty in five cases and deleted keratoplasty in nine cases. Final visual acuity was equal to or better than at admission in 81% of cases. Anatomic loss of the eye was observed in eight cases (evisceration, six cases; enucleation, two cases). CONCLUSION: microbial keratitis is a frequent and severe pathology that can lead to blindness. Only early and adapted management can improve the prognosis of severe microbial keratitis.

The design of cationic lipids for gene delivery.

Synthetic gene delivery vectors are gaining increasing importance in gene therapy as an alternative to recombinant viruses. Among the various types of non-viral vectors, cationic lipids are especially attractive as they can be prepared with relative ease and extensively characterised. Further, each of their constituent parts can be modified, thereby facilitating the elucidation of structure-activity relationships. In this forward-looking review, cationic lipid-mediated gene delivery will mainly be discussed in terms of the structure of the three basic constituent parts of any cationic lipid: the polar headgroup, hydrophobic moiety and linker. Particular emphasis will be placed on recent advances in the field as well as on our own original contributions. In addition to reviewing critical physicochemical features (such as headgroup hydration) of monovalent lipids, the use of headgroups with known nucleic-acid binding modes, such as linear and branched polyamines, aminoglycosides and guanidinium functions, will be comprehensively assessed. A particularly exciting innovation in linker design is the incorporation of environment-sensitive groups, the intracellular hydrolysis of which may lead to more controlled DNA delivery. Examples of pH-, redox- and enzyme-sensitive functional groups integrated into the linker are highlighted and the benefits of such degradable vectors can be evaluated in terms of transfection efficiency and cationic lipid-associated cytotoxicity. Finally, possible correlations between the length and type of hydrophobic moiety and transfection efficiency will be discussed. In conclusion it may be foreseen that in order to be successful, the future of cationic lipid-based gene delivery will probably require the development of sophisticated virus-like systems, which can be viewed as "programmed supramolecular systems" incorporating the various functions required to perform in a chronological order the different steps involved in gene transfection.

Forensic medicine in Tunisia.

Tunisia is an Arab northern African country which counts 10 millions citizens. In Tunisia, there is a small number of forensic practitioners (20) distributed over four University and two regional Hospitals. Forensic activity is under the supervision of Tunisian Ministry of Public Health. The first forensic medicine department was set up in the Faculty of Medicine of Tunis (the capital) in the sixties, after which three other departments were founded in medical faculties and in their respective university hospitals (Sfax, Sousse and Monastir). These departments provide forensic medical education and research beside their daily practice. Forensic medical practice is divided in forensic pathology and clinical forensic medicine. In forensic pathology, we have to deal with violent or suspected deaths beside natural deaths. The clinical forensic medicine activity covers mainly forensic traumatology. Other fields of forensic sciences are in progress and ought to be developed all over the country. A forensic medical curriculum is provided in the four Tunisian Faculties of Medicine and in their University Hospitals. Nevertheless, the number of trainees remains small and could not currently satisfy the country needs.

[Modulation of experimental myasthenia gravis by IVIg]. / Modulation de la myasthénie expérimentale par les IgIV.

Myasthenia Gravis (MG) is an autoimmune disease mediated by antibodies directed against the acetylcholine receptor (AChR). Treatment by IVIg is effective in acute forms of myasthenia gravis. In order to determine the in vivo effects of the various fractions of human immunoglobulins, we used an experimental model of myasthenia gravis in SCID mice. To this end, thymic cells from MG patients are transferred to these mice according to a well defined protocol. When establishing of the model, we noticed the appearance of anti-AChR antibodies and the loss of AChR expression at the muscle level. After treatment with IVIgG or IVIgM, the mice displayed a lower anti-AChR antibody titer compared to control mice (albumin treated) and the loss of the AChR number at the muscle was significantly reduced. These results obtained from one MG patient indicate that the human immunoglobulin preparations induce significant effects on pathogenic parameters in the SCID mouse model. Therefore this model is interesting to approach the mechanisms of action of human immunoglobulins and deserves further investigation.

Prevention of autoimmune attack by targeting specific T-cell receptors in a severe combined immunodeficiency mouse model of myasthenia gravis.

Myasthenia gravis (MG) is an autoimmune disease targeting the skeletal muscle acetylcholine receptor. We have previously demonstrated a selection bias of CD4+ T cells expressing the Vbeta5.1 T-cell receptor gene in the thymus of HLA-DR3 patients with MG. To evaluate the pathogenicity of these cells, severe combined immunodeficiency mice engrafted with MG thymic lymphocytes were treated with anti-Vbeta5.1 antibody. Signs of pathogenicity (eg, acetylcholine receptor loss and complement deposits at the muscle end plates of chimeric mice) were prevented in anti-Vbeta5.1-treated severe combined immunodeficiency chimeras. Pathogenicity was mediated by autoantibodies against acetylcholine receptor. Thymic cells depleted of Vbeta5.1-positive cells in vitro before cell transfer were nonpathogenic, indicating that Vbeta5.1-positive cells are involved in the production of pathogenic autoantibodies. Acetylcholine receptor loss was prevented by Vbeta5.1 targeting in HLA-DR3 patients only, demonstrating specificity for HLA-DR3-peptide complexes. The action of the anti-Vbeta5.1 antibody involved both the in vivo depletion of Vbeta5.1-expressing cells and an increase in the interferon-gamma/interleukin-4 ratio, pointing to an immune deviation-based mechanism. This demonstration that a selective and specific T-helper cell population is involved in controlling pathogenic autoantibodies in MG holds promise for the treatment of MG.

Normal human immunoglobulin suppresses experimental myasthenia gravis in SCID mice.

Serum IgM has been shown to participate in the control of IgG autoreactivity in healthy subjects. We have recently shown that an immunoglobulin preparation of pooled normal human IgM (IVIgM) contains anti-idiotypic antibodies against disease-associated IgG autoantibodies in autoimmune patients and protects rats from experimental autoimmunity. The aim of the present study was to asses the in vitro and in vivo immunomodulatory effects of IVIgM in comparison with IgG, in SCID mice reconstituted with thymic cells from a myasthenia gravis patient. Non-leaky SCID mice were injected i.p. with 60 x 10(6) thymic cells from a patient with myasthenia gravis and 1 day later boosted with 10(6) irradiated acetylcholine receptor (AchR)-expressing TE671 cells. On days 14, 21 and 28, mice were treated with IVIgM or with equimolar amounts of human serum albumin. The level of anti-AchR antibodies in the sera of three out of four IgM-treated animals was less than 1 nM. Further, there was a significant decrease in the loss of endplate AchR on the diaphragms of IgM-treated SCID mice. These findings indicate that pooled normal IgM exerts an immunoregulatory role in experimental myasthenia gravis, and suggests that IgM may be considered as an alternative approach in the therapy of autommune diseases.

Is the short-term modulation if heart rate in teleost fish physiologically significant? Assessment by spectral analysis techniques

Heart rate is an important physiological variable in the control of cardiac output, even in fishes, where the importance of stroke volume has been overemphasized. Except for the myxinoids, the fish heart is innervated by cranial nerve X and the nature of this innervation is mainly inhibitory by parasympathetic fibers, although a sympathetic contribution has also been demonstrated. In mammals, cardiac innervation is not only responsible for the control of mean heart rate but it also modulates the beat-to-beat heart rate changes. These beat-to-beat changes are known as heart rate variability (HRV) and appear to be related to fluctuations in respiration and blood pressure. In this paper we demonstrate the link between cardiac innervation and HRV in several species of teleosts because HRV is greatly decreased after vagotomy or atropinization. In contrast, after abolishing the sympathetic influence with propranolol, only slight changes in total HRV are observed, indicating the restricted importance of the adrenergic innervation in determining phasic changes in HRV despite the significant tonic effect which has been demonstrated. Thus, it appears unlikely that the sympathetic influence will be present in any measured spectral component as suggested previously. Furthermore, clear spectral patterns do not always exist and this may be due to the erratic influence of respiration which is clearly faster than heart rate in all fish species studied. This differs from the slow ventilation frequency displayed by many mammalian species that exerts an influence on a beat-to-beat basis (respiratory sinus arrhythmia). Spectral patterns could also be affected by changing levels of circulating catecholamines, although this is still unproved.

Is the short-term modulation of heart rate in teleost fish physiologically significant? Assessment by spectral analysis techniques.

Heart rate is an important physiological variable in the control of cardiac output, even in fishes, where the importance of stroke volume has been overemphasized. Except for the myxinoids, the fish heart is innervated by cranial nerve X and the nature of this innervation is mainly inhibitory by parasympathetic fibers, although a sympathetic contribution has also been demonstrated. In mammals, cardiac innervation is not only responsible for the control of mean heart rate but it also modulates the beat-to-beat heart rate changes. These beat-to-beat changes are known as heart rate variability (HRV) and appear to be related to fluctuations in respiration and blood pressure. In this paper we demonstrate the link between cardiac innervation and HRV in several species of teleosts because HRV is greatly decreased after vagotomy or atropinization. In contrast, after abolishing the sympathetic influence with propranolol, only slight changes in total HRV are observed, indicating the restricted importance of the adrenergic innervation in determining phasic changes in HRV despite the significant tonic effect which has been demonstrated. Thus, it appears unlikely that the sympathetic influence will be present in any measured spectral component as suggested previously. Furthermore, clear spectral patterns do not always exist and this may be due to the erratic influence of respiration which is clearly faster than heart rate in all fish species studied. This differs from the slow ventilation frequency displayed by many mammalian species that exerts an influence on a beat-to-beat basis (respiratory sinus arrhythmia). Spectral patterns could also be affected by changing levels of circulating catecholamines, although this is still unproved.

Computing heart rate variability using spectral analysis techniques: HRVUAB, a ready-to-use program.

The application of spectral analysis techniques to study the nervous modulation of the vertebrate heart have given interesting results in clinical studies although nearly nothing is known in lower vertebrates. A program to compute this heart rate variability is described in detail and preliminary results are shown. Data is first statistically qualified and fragmented in smaller segments, each being further processed through linear trend removal and normalization before the application of the Fast Fourier Transform algorithm to estimate the interval spectrum. All consecutive periodograms are averaged and the interval spectrum plotted and saved.

[Hodgkin's disease of the lung with cavitation and apparently primary. Apropos of a case]. / Maladie de Hodgkin à localisation pulmonaire excavée apparemment primitive. A propos d'un cas.

The authors report a rare and diagnostically difficult clinical case of primary pulmonary Hodgkin's disease, with cavitation. They stress the diagnostic difficulties which they encountered: Indeed four stages are described in this case in which different diagnoses were considered as follows, a primary or secondary lung cancer, non-specific pulmonary suppuration, atypical hydated disease (as is frequently seen in Algeria) and finally pulmonary tuberculosis. The diagnosis of Hodgkin's disease was not considered until post-mortem. A review of the literature has called attention to the great rarity of cavitating Hodgkin's disease (only 53 cases in the world published). A clinical, radiological and anatomical study of the principal case published enhances the commentary on this rare case. In addition the pathogenesis of this granulomatous necrosis in Hodgkin's disease is discussed.