Sperm fluorescent in situ hybridisation study of interchromosomal effect in six Tunisian carriers of reciprocal and Robertsonian translocations.

Carriers of structural chromosomal anomalies, translocations and inversions are at increased risk of aneuploid gametes production. Besides the direct effect on the involved chromosomes, these rearrangements might disturb the segregation of other structurally normal chromosomes during meiosis. Such event is known as interchromosomal effect. In this study, six male carriers of translocations, four reciprocals and two Robertsonians, were investigated. In addition, seven fertile men with normal 46,XY karyotypes and normal sperm characteristics were enrolled as a control group. Spermatic fluorescent in situ hybridisation specific for chromosomes X, Y, 18, 21 and 22 was carried out. The Mann-Whitney U-test was used to compare the aneuploidy rates between patients and controls. All translocation carriers showed significantly increased frequencies of disomy of all investigated chromosomes, and diploid gametes compared with the control group (p < .05). However, disomy XY was not significantly different between controls and patients (p > .05). We have also observed a considerable interindividual variability in disomy and diploidy rates. These results confirm that the interchromosomal effect seems to exist and could contribute to higher rates of abnormal prenatal aneuploidy, resulting in a small increase in the risk of miscarriage and birth of children with congenital abnormalities and a potential reduction in fertility.

NOBOX is a strong autosomal candidate gene in Tunisian patients with primary ovarian insufficiency.

Premature ovarian insufficiency (POI) affects approximately 1% of women before the age of 40. Genetic contribution is a significant component of POI. In this context, heterozygous mutations in NOBOX, BMP15 and GDF9 have been reported. The objective of our study was to evaluate the prevalence of these genes mutations in 125 unrelated Tunisian patients diagnosed with POI. The screening of NOBOX gene revealed three missense mutations (p.Arg117Trp; p.Gly91Trp and p.Pro619Leu) in eight patients. These mutations were not found in a 200 ethnically matched women without fertility problem. The sequencing of BMP15 and GDF9 gene revealed only previously reported variants. In contrast to previous studies, the prevalence of BMP15 variations is not higher than in the control population. Conversely, 6.4% of the cases present a NOBOX mutations; this high prevalence strengthens the consideration of NOBOX gene as strong autosomal candidate for POI.

Multiscale analysis of Klf10's impact on the passive mechanical properties of murine skeletal muscle.

Skeletal muscle is a hierarchical structure composed of multiple organizational scales. A major challenge in the biomechanical evaluation of muscle relates to the difficulty in evaluating the experimental mechanical properties at the different organizational levels of the same tissue. Indeed, the ability to integrate mechanical properties evaluated at various levels will allow for improved assessment of the entire tissue, leading to a better understanding of how changes at each level evolve over time and/or impact tissue function, especially in the case of muscle diseases. Therefore, the purpose of this study was to analyze a genetically engineered mouse model (Klf10 KO: Krüppel-Like Factor 10 knockout) with known skeletal muscle defects to compare the mechanical properties with wild-type (WT) controls at the three main muscle scales: the macroscopic (whole muscle), microscopic (fiber) and submicron (myofibril) levels. Passive mechanical tests (ramp, relaxation) were performed on two types of skeletal muscle (soleus and extensor digitorum longus (EDL)). Results of the present study revealed muscle-type specific behaviors in both genotypes only at the microscopic scale. Interestingly, loss of Klf10 expression resulted in increased passive properties in the soleus but decreased passive properties in the EDL compared to WT controls. At the submicron scale, no changes were observed between WT and Klf10 KO myofibrils for either muscle; these results demonstrate that the passive property differences observed at the microscopic scale (fiber) are not caused by sarcomere intrinsic alterations but instead must originate outside the sarcomeres, likely in the collagen-based extracellular matrix. The macroscopic scale revealed similar passive mechanical properties between WT and Klf10 KO hindlimb muscles. The present study has allowed for a better understanding of the role of Klf10 on the passive mechanical properties of skeletal muscle and has provided reference data to the literature which could be used by the community for muscle multiscale modeling.

Tunisian endemic pemphigus foliaceus is associated with the HLA-DR3 gene: anti-desmoglein 1 antibody-positive healthy subjects bear protective alleles.

BACKGROUND: Pemphigus foliaceus is an autoimmune blistering skin disease that partly results from genetic factors, especially human leucocyte antigen (HLA) class II genes. OBJECTIVES: The aim of the study was to determine the HLA DR/DQ markers of susceptibility and protection in the Tunisian endemic form. METHODS: Genomic DNA from 90 patients with pemphigus foliaceus recruited from all parts of the country and matched by age, sex and geographical origin with 270 healthy individuals, was genotyped. RESULTS: Firstly, when the whole patient population was studied, DRB1*03, DQB1*0302 and DRB1*04 alleles were significantly associated with the disease while a significant decrease of, in particular, DRB1*11 and DQB1*0301 was observed in patients compared with controls. DRB1*0301 was the dominant allele in DR3-positive patients and controls, while DRB1*0402 was found in 42% of DR4-positive patients. Secondly, when the HLA DR/DQ allele distribution was studied after dividing patients according to their geographical origin, the southern group, which consisted exclusively of patients with the endemic form of the disease, showed the same associations as the whole pemphigus foliaceus population, particularly with DRB1*03. In the northern group, only the DRB1*04 and DQB1*0301 alleles were found to be associated. Interestingly, anti-desmoglein 1 antibody-positive healthy controls did not carry susceptibility alleles but, in contrast, most carried negatively associated alleles. CONCLUSIONS: These observations indicate that a particular genetic background characterizes the Tunisian endemic form of pemphigus foliaceus and that HLA class II genes control the pathogenic properties of the autoimmune response rather than the initial breakage of B-cell tolerance.

Anti-desmoglein 1 antibodies in healthy related and unrelated subjects and patients with pemphigus foliaceus in endemic and non-endemic areas from Tunisia.

BACKGROUND: Pemphigus foliaceus is an autoimmune blistering skin disease characterized by the production of pathogenic IgG autoantibodies directed against desmoglein 1. AIM: To determine the prevalence of anti-desmoglein 1 antibodies in healthy subjects and their distribution in the different regions of Tunisia and to better identify endemic areas of pemphigus foliaceus. METHODS: We tested, by enzyme-linked immunoserbent assay, sera of 270 normal subjects recruited from different Tunisian areas and 203 related healthy relatives to 90 Tunisian pemphigus foliaceus patients. Results Seventy-six patients (84.4%), 20 healthy controls (7.4%), and 32 relatives (15.76%) had anti-desmoglein 1 antibodies. In southern regions where pemphigus foliaceus is associated with a significant sex ratio imbalance (9 female : 1 male in the south vs. 2.3 : 1 in the north) and a lower mean age of disease onset (33.5 in the south vs. 45 years in the north), a higher prevalence of anti-desmoglein 1 antibodies in healthy controls was observed (9.23% vs. 5.71% in the north). Interestingly, the highest prevalence of anti-desmoglein 1 antibodies in healthy relatives (up to 22%) was observed in the most rural southern localities. More than half anti-desmoglein 1-positive healthy controls were living in rural conditions with farming as occupation, which suggests that this activity may expose the subjects to particular environmental conditions. CONCLUSION: These results show that the endemic features of Tunisian pemphigus foliaceus are focused in these southern areas more than in other areas and that both environmental and genetic factors contribute to the disease.

The Effect of Freezing Time on Muscle Fiber Mechanical Properties.

The purpose of this study was to investigate the effect of freezing time on the functional behavior of mouse muscle fibers. Passive mechanical tests were performed on single soleus muscle fibers from fresh (0 month) and preserved (stored at -20°C for 3, 6, 9 and 12 months) 3 month old mice. The Young's modulus and the dynamic and the static stresses were measured. A viscoelastic Hill model of 3rd order was used to fit the experimental relaxation test data. The statistical analysis corresponding to the elastic modulus of single muscle fibers did not differ when comparing fresh and stored samples for 3 and 6 months at -20 °C. From 9 months, fibers were less resistant and the mechanical properties were damaged. The primary goal of this study was to complete the gold standard process of muscle fiber preservation for subsequent mechanical property studies. We have demonstrated that muscle fibers can be stored at -20°C for up to 6 months without altering their mechanical properties.

[Study of the ploidy and cellular cycle of hidradenomas and hidradenocarcinomas: a series of 13 cases]. / Etude de la ploïdie et du cycle cellulaire des hidradenomes et des hidradenocarcinomes: a propos d'une série de 13 cas.

AIMS: To study by flow cytometry (FCM) the ploidy and the cellular cycle of nodular hidradenoma (NH) and hidradenocarcinoma (HC) and to assess the prognostic utility of this technique in such tumors. METHODS: We studied retrospectively 2 HC and 11 NH one of which was considered as an atypical NH. Monoparametric study by FCM was realized on paraffin-embedded material. The extracted cells were marked by Propidium's lodure and cellular cycle was analyzed by the software Mod-Fit LT. RESULTS: Our study showed eleven 100% diploid profiles, 10 of which had low S-phase varying between 2 and 12%. All of these 11 tumors were NH. S-phase was high (23.79%) in a single case that corresponded to the atypical NH. Two tumors showed aneuploid profiles; these corresponded to the 2 HC. CONCLUSION: The results of the cytometric study suit perfectly to those of the histopathologic examination. FCM could so help to establish the prognosis of these tumors. But further studies are necessary to determine the value of this technique.

Severe scorpion envenomation: pathophysiology and the role of inflammation in multiple organ failure.

Scorpion stings occur on every continent except Antarctica. The correlation between young age and severity of clinical manifestations after this envenomation is well-established. Several studies have emphasized the relevance of pro-inflammatory mediators in the pathophysiological manifestations of human scorpion envenomation. Moreover, there is a significant association between pro-inflammatory cytokine levels in the blood and the severity of scorpion envenomation. Release of these cytokines increases the severity of the visceral damage induced by the direct action of the venom and the activation of both the sympathetic and parasympathetic nervous systems.

[Bilateral proximal pulmonary embolism without associated hypoxemia. Case report]. / Embolie pulmonaire proximale bilatérale sans hypoxémie associée. À propos d'un cas.

INTRODUCTION: Pulmonary embolism is a classic complication in intensive care. It is characterized by hypoxemia secondary to perturbed ventilation/perfusion ratios. We report a case of proximal and bilateral pulmonary embolism that occurred without associated hypoxemia. A spiral computed tomography (CT) scan was performed to explore unexplained fever in a patient with a negative infectious investigation. We discuss the mechanisms underlying the absence of hypoxemia in this patient. CLINICAL CASE: A 43-year-old patient with no significant pathological history was admitted to intensive care for the management of multiple injuries following a road accident. During resuscitation, the patient developed a proximal and bilateral pulmonary embolism without signs of hypertension of the pulmonary artery or associated hypoxemia. The patient improved under treatment. DISCUSSION: This case shows that bilateral proximal pulmonary embolism may be associated with normal gas exchange. The absence of hypoxemia could be explained by the bilateral nature of the pulmonary embolism that led to balanced ventilation/perfusion ratios on both sides. Furthermore, bronchoconstriction was bilateral, explaining the maintenance of a stable ventilation/perfusion ratio on both sides. CONCLUSION: The presence of unexplained fever in a victim of multiple trauma, despite the absence of hypoxemia, suggests the diagnosis of pulmonary embolism.

[Epidemiological features and complications of central venous catheters in pediatric oncology: prospective study about 125 cases]. / Profil épidémiologique et complications des voies veineuses centrales en oncologie pédiatrique: à propos de 125 cas.

OBJECTIVE: To report the indications and early and late catheter-related complications in a Tunisian unit of paediatric oncology. PATIENTS AND METHODS: This prospective study has been performed in a paediatric oncology unit of the Salah Azaïz Institute between 1989 and 2005. It concerns 58 girls and 57 boys with a median age of 7.9 years(4 months to 18 years) treated for cancer disease predominantly lymphoma (22%), sarcoma (23.2%) or leukaemia (8.5%) proposed for insertion of a central venous catheter (CVC). RESULTS: Excluding 2 insertion failures (1.6%), we placed 123 CVC (double for 10 patients), 43 (35%) exteriorised (EC) and 80 (65%) connected to an implantable site (IS). Catheters were placed in the subclavian vein in 59.2% of cases vs 32% for internal jugular vein and 8.8% for femoral vein. Early complications included 15 cases of multiple punctures (12%), 4 cases of pneumothorax (3.2%) and 6 of arterial punctures (4.8%) originating a cervical subcutaneous haematoma in 1 patient (0.8%). Late complications were represented by infection in 7 cases (5.7%). We observed 2 cases of intracardiac catheter migration due to catheter disconnection from the IS (1.6%) and 2 cases of thrombosis (1.8%). The mean life of CVC was longer for IS (305.2 days) than for EC (64.4 days). CONCLUSION: Implantable sites are effective progress for venous access in children with cancer. They improved the quality of care in pediatric oncology.

Flexible thin-film battery based on graphene-oxide embedded in solid polymer electrolyte.

Enhanced safety of flexible batteries is an imperative objective due to the intimate interaction of such devices with human organs such as flexible batteries that are integrated with touch-screens or embedded in clothing or space suits. In this study, the fabrication and testing of a high performance thin-film Li-ion battery (LIB) is reported that is both flexible and relatively safer compared to the conventional electrolyte based batteries. The concept is facilitated by the use of solid polymer nanocomposite electrolyte, specifically, composed of polyethylene oxide (PEO) matrix and 1 wt% graphene oxide (GO) nanosheets. The flexible LIB exhibits a high maximum operating voltage of 4.9 V, high capacity of 0.13 mA h cm(-2) and an energy density of 4.8 mW h cm(-3). The battery is encapsulated using a simple lamination method that is economical and scalable. The laminated battery shows robust mechanical flexibility over 6000 bending cycles and excellent electrochemical performance in both flat and bent configurations. Finite element analysis (FEA) of the LIB provides critical insights into the evolution of mechanical stresses during lamination and bending.

Microglial chimaerism in human xenografts to the rat brain.

Neural tissue from human fetuses is currently used for intracerebral transplantation to treat patients with Parkinson's disease. The development of the human fetal tissue following grafting has been considered mostly, up to now, from the neuronal point of view in xenografts. Very little is known, in contrast, about nonneuronal, glial, or vascular cells in the grafts. Comparison of the data gathered on the development of grafted human neurons with those obtained in comparable studies using rat transplants has demonstrated species-specific features. We have therefore undertaken a series of studies dealing with nonneuronal cells in human-to-rat transplants to reveal other possible species-specificity of the human tissue. This study has, accordingly, been devoted to the immunohistochemical analysis of microglia of host and donor origins in a human to rat xenograft paradigm allowing clear distinction of the origin of the cells. Human neural tissue was transplanted as a cell suspension into the thalamus of adult rats. Amoeboid human microglia were observed in 1-, 2-, and 3-month-old transplants, but their density, already relatively low at the first stage, decreased further over time. Ramified human microglia were only occasional. In sharp contrast, host rat microglia rapidly invaded the transplant in the absence of any sign of necrosis. The rat cells exhibited first an amoeboid morphology but progressed at the later stages toward a more mature, ramified morphology. These results indicate that donor microglia are quite few in number at first and, at least, do not proliferate actively after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Primary osteosarcoma of the cervical spine: one case.

The authors report the case of a 31-year old woman who was operated upon for cervical bone tumour. The pathological study showed that it was a primary, highly differentiated osteosarcoma. The clinical picture was limited to a spinal cord compression syndrome without signs of inflammation. Radiological findings were non-specific. Treatment consisted of laminectomy, radiotherapy and chemotherapy. The course of the disease was marked by stabilization, then rapid aggravation 2 years after the operation. A review of the literature highlighted the rarity and relatively slow progression of primary osteosarcomas of the spine.

[Therapeutic results of 5-fluorouracil in multiple and unresectable facial carcinoma secondary to xeroderma pigmentosum]. / Résultats thérapeutiques du 5-fluorouracile dans les carcinomes multiples ou non resécables de la face secondaires au xeroderma pigmentosum (XP).

A prospective study was done to test the efficacy of 5-fluorouracil (topical and systemic) in multiple and unresectable histologically proven facial squamous cell carcinomas (SCC) secondary to XP. Twelve patients (7M/5F, mean age 19.8 years) with multiple facial SCC were treated between 1994 and 1997. 5-FU was used as a twice-a-day local application in the documented areas, by continuous infusion associated with cisplatin (2 patients) and short infusion combined with folic acid (3 patients). Evaluation was done by clinical examination every two months for topical therapy and after every cycle for systemic treatment. Median treatment duration was 12 months (2 to 36 months). Treatment was well tolerated excluding episodes of pruritus in the treated areas. We observed mainly superficial tumour regression followed by dryness and crusting. In 5 cases, we performed biopsies after treatment showing in one case an extensive fibrosis with absence of tumour. However in the remaining 4 cases, despite a superficial reduction of tumour and a reconstitution of the epidermis, viable and unmodified squamous cell carcinoma remained in the deeper dermis. In the 5 patients treated by systemic 5-FU, we observed 1 complete response and 3 partial responses. Despite a dissociation between a good cosmetic result and a relatively superficial effect, topical 5-FU represents a useful therapeutic option in multiple unresectable facial SCC in patients with XP. Systemic chemotherapy is recommended in the event of more extended or profound lesions.

[Hypothyroid dilated cardiomyopathy]. / Myocardiopathie dilatée d'origine myxoedémateuse.

Most patients with dilated cardiomyopathy have a poor prognosis due to progressive and irreversible myocardial dysfunction. Rarely, is a metabolic etiology responsive to specific therapy identified. Although many studies have confirmed that thyroid hormone deficiency is associated with a reversible decrease in myocardial contractility, it has remained controversial whether hypothyroidism alone can cause a dilated cardiomyopathy and clinical heart failure. In this study, we report the case of a patient with severe hypothyroidism and a dilated cardiomyopathy complicated by heart failure, which has receded after recovery to euthyroidism with L-thyroxin therapy. This case suggests that hypothyroidism should be evoked systematically when a dilated cardiomyopathy is diagnosed.

[Diagnostic and therapeutic thoracoscopy in 83 cases of chronic pleurisy]. / Thoracoscopie diagnostique et thérapeutique dans 83 cas de pleurésies chroniques.

From May 1983 to June 1985 the authors performed a thoracoscopy as a diagnostic and therapeutic objective in 83 patients with chronic recurrent pleurisy; amongst these patients, 69 had know intra or extra thoracic cancer and the other 14 presented with an isolated pleurisy. Eight other patients had pleural carcinomatosis proven by needle biopsy and had pleural talc introduced by thoracoscopy. The examination was performed under local anaesthesia with neuroleptanalgesia; a rigid 7 mm diameter thoracoscope was used; the biopsies were performed uniquely on the parietal pleura using tropical forceps. The outcome was uncomplicated with no deaths nor any serious complications due to the method. The sensitivity of the pleural biopsy was 91.5% or 76 positive biopsies out of 83. 73 biopsies were metastatic and 3 were tuberculous pleurisies. The macroscopic appearance was strongly suggestive of malignancy in 78 patients and appeared inflammatory in 13, of whom 9 cases were positive on biopsy. The authors performed a pleural talcage in every case; a lasting pleural adhesion was obtained in 66 patients but regrettably there were 14 failures, the effusion recurring after removal of the drain. The authors stress the reduced number of incidents of pleural effusion, which confirms the good tolerance of pleural endoscopy.

[Prevalence and clinical aspects of superficial mycosis in hospitalized diabetic patients in Tunisia]. / Prevalence et aspects cliniques des mycoses superficielles chez le diabétique tunisien en milieu hospitalier.

OBJECTIVES: The prevalence of mycotic infection seems to be higher among diabetic patients than in the non-diabetic population. The aims of this study were to determine the frequency of mycosis and to compare clinical and fungal results. PATIENTS AND METHODS: This transversal study included 307 type 1 and 2 diabetic patients admitted between January 1998 and January 2000. A dermatologist examined all patients. The mean age was 44 +/- 17 years and the duration of diabetes 8 +/- 6 years. Patients with suspected lesions underwent mycological examination. RESULTS: Clinical signs of presumed fungal infection were found in 61% of patients, but mycosis was confirmed only in 30%. Fungal foot infection accounted 38% of the patients, mostly due to dermatophytes (94%). The commonest localizations of dermatophytes were interdigital (60%) followed by onychomycosis (30%). The main fungal agent was Trichophyton rubrum. The main risk factors for fungal infections were the age of patients (P = 0.0003) and duration of diabetes (P < 0.05). Interdigital foot localization of dermatophytes was correlated to age (P < 0.0001) and to the male gender (P < 0.01). The frequency of dermatophytes in nails was higher in type 2 diabetic patients (P < 0.01). Vulvovaginal candidosis and interdigital dermatophytes were more frequent in obese than in non-obese patients. The accuracy and specificity of direct examination were respectively 85% and 79%. CONCLUSION: The high frequency of mycosis in diabetic patients at hospital is demonstrated. The main risk factors were age, male gender and obesity.

[Hydatid pulmonary embolism. Two case reports]. / Embolies pulmonaires hydatiques. A propos de deux cas.

Hydatid pulmonary embolism is an uncommon condition resulting from the rupture of a hydatid heart cyst or the opening of a visceral hydatid cyst (often in the liver) into the venous circulation. We report two cases of hydatid pulmonary embolism following rupture of a hydatic cyst in the right ventricle. One case progressed to chronic cor pulmonale. We examine the pathophysiological mechanisms as well as the clinical, therapeutic and evolutive aspects.

A simplified immunohistochemical classification of skeletal muscle fibres in mouse.

The classification of muscle fibres is of particular interest for the study of the skeletal muscle properties in a wide range of scientific fields, especially animal phenotyping. It is therefore important to define a reliable method for classifying fibre types. The aim of this study was to establish a simplified method for the immunohistochemical classification of fibres in mouse. To carry it out, we first tested a combination of several anti myosin heavy chain (MyHC) antibodies in order to choose a minimum number of antibodies to implement a semi-automatic classification. Then, we compared the classification of fibres to the MyHC electrophoretic pattern on the same samples. Only two anti MyHC antibodies on serial sections with the fluorescent labeling of the Laminin were necessary to classify properly fibre types in Tibialis Anterior and Soleus mouse muscles in normal physiological conditions. This classification was virtually identical to the classification realized by the electrophoretic separation of MyHC. This immunohistochemical classification can be applied to the total area of Tibialis Anterior and Soleus mouse muscles. Thus, we provide here a useful, simple and time-efficient method for immunohistochemical classification of fibres, applicable for research in mouse.