Low-voltage DEP microsystem for submicron particle manipulation in artificial cerebrospinal fluid.

In this paper, we present a new low voltage biochip for micro and nanoparticle separation. The proposed system is designed to detect the concentration of particles after being separated through reconfigurable DEP-based electrode architecture. The described system in this work is focusing on the particle frequency dependent separation. Experimental results in artificial cerebrospinal fluid (ACSF) show that each particle has its own crossover frequency. Thus based on the crossover frequency, particles are attracted to the electrode's surface, while others are pushed away. Five different particles are tested with different diameters in the range of 500 nm to 4 µm. All separation process is controlled by a CMOS chip fabricated using 0.18 µm technology from TSMC and powered with 3.3 V. Efficient particle separation is observed with low voltage, below 3.3V unlike other techniques in the range of kV. The proposed platform includes an advanced PDMS based assembly technique for fast testing and prototyping in addition to reconfigurable electrode architecture.

Hybrid modeling method for a DEP based particle manipulation.

In this paper, a new modeling approach for Dielectrophoresis (DEP) based particle manipulation is presented. The proposed method fulfills missing links in finite element modeling between the multiphysic simulation and the biological behavior. This technique is amongst the first steps to develop a more complex platform covering several types of manipulations such as magnetophoresis and optics. The modeling approach is based on a hybrid interface using both ANSYS and MATLAB to link the propagation of the electrical field in the micro-channel to the particle motion. ANSYS is used to simulate the electrical propagation while MATLAB interprets the results to calculate cell displacement and send the new information to ANSYS for another turn. The beta version of the proposed technique takes into account particle shape, weight and its electrical properties. First obtained results are coherent with experimental results.

Contribution of Hla-B51 in the susceptibility and specific clinical features of Behcet's disease in Tunisian patients.

BACKGROUND: Many researchers have tried to investigate the association of HLA-B51 with the severity and the clinical features of BD with conflicting results. METHODS: We aimed at investigating the association of HLA-B51 with demographical and clinical manifestations as well as the severity of BD, by studying 178 native Tunisian BD patients, fulfilling the International Study group criteria for the BD classification recruited from the Department of Internal Medicine, Rabta Hospital in Tunis and compared with 125 native Tunisian healthy age and sex matching volunteers. RESULTS: According to our findings, the frequency of HLAB 51 was significantly higher in BD patients than in controls (p<0.001). Positive pathergy test (PPT) (p = 0.01) and retinal vasculitis (p = 0.045), were significantly more frequent in HLA B51(+) patients, while the frequency of arterial aneurysms (p = 0.009) and neurological involvement, especially the parenchymal involvement (p<0.001), were significantly and clearly higher in HLA B51(-) patients. The patients without HLA B51 had a significantly less severe disease (p = 0.001). Discussion/conclusion We conclude that HLA B51 is a predisposing marker for BD in our population as in most ethnic groups. It seems to be associated with a subgroup of BD patients characterized by a higher frequency of ocular involvement and PPT, but a lower frequency of arterial aneurysm and neurological involvement, and a less severe disease course.

Electrode robustness in artificial cerebrospinal fluid for dielectrophoresis-based LoC.

In this paper, we present hybrid microelectronics / microfluidic Lab-on-Chip (LoC) platform intended for implantable medical microsystems for neurotransmitter detection. In vitro experiments were achieved using artificial cerebrospinal fluid (ACSF) from Tocris Bioscience where microspheres were immersed to test the behaviour of the designed LoC. One of main features of the proposed LoC platform is its thin thickness, including micro-channels and silicon CMOS chip. The latter is integrated into the glass top-layer of the LoC measuring 0.5 mm. The size of the device is 9 mm × 5 mm. the electrode architecture is composed of 8×2×2 L-shaped electrodes in a 650 µm channel width and 4 sites for interdigitited electrodes. 32 L-shaped electrodes were connected to a electronics circuit for cells manipulation using dielectrophoresis (DEP). The described LoC achieved an efficient separation within a concentration of 50 µl of a solution of microspheres, distilled water (DW) and 500 µl of ACSF. Beyond this concentration, electrode destruction was observed.

Dielectrophoresis-based integrated Lab-on-Chip for nano and micro-particles manipulation and capacitive detection.

We present in this paper a new Lab-on-Chip (LoC) architecture for dielectrophoresis-based cell manipulation, detection, and capacitive measurement. The proposed LoC is built around a CMOS full-custom chip and a microfluidic structure. The CMOS chip is used to deliver all parameters required to control the dielectrophoresis (DEP) features such as frequency, phase, and amplitude of signals spread on in-channel electrodes of the LoC. It is integrated to the LoC and experimental results are related to micro and nano particles manipulation and detection in a microfluidic platform. The proposed microsystem includes an on-chip 27-bit frequency divider, a digital phase controller with a 3.6° phase shift resolution and a 2.5 V dynamic range. The sensing module is composed of a 3 × 3 capacitive sensor array with 10 fF per mV sensitivity, and a dynamic range of 1.5 V. The obtained results show an efficient nano and micro-particles (PC05N, PA04N and PS03N) separation based on frequency segregation with low voltages less than 1.7 V and a fully integrated and reconfigurable system.

Does lowering hyperhomocysteinemia by folic acid beneficial for oculo-Behcet's disease? A pilot study.

OBJECTIVE: To determine the effect of folic acid supplementation in Behçet's disease (BD) patients with ocular involvement associated with hyperhomocysteinemia (Hhcys). PATIENTS AND METHODS: 19 BD patients, all with uveitis and/or retinal vasculitis associated with Hhcys (plasma hcy > 15 micromol/l) were prospectively included. Patients were divided into 2 groups. Group 1 consisted of 11 patients that received folic acide (15 mg/d) in addition to their previous standard treatment. Group 2 included 8 patients treated only with their previous standard treatment. Visual acuity and uveitis attacks were assessed initially and monthly at each visit in all groups. Mean Visual acuity and frequency of uveitis attacks were evaluated quarterly. RESULTS: In group 1, the mean plasma hcys level was significantly lower after than before the treatment period (27.7 vs 13.1 micromol/l; p= 0.04) while it did not vary significantly in the same period in Group 2 patients. Frequency of uveitis attacks was significantly lower after than before treatment at each quarter in groupl and mean visual acuity in this group increased from 4.33 to 5.44 decimals. During the treatment period, the mean number of uveitis attacks, converted to frequency per 12 months were significantly lower in group 1 than in group 2. During this period, the VA slightly increased in group 1 and decreased in group 2 but the difference was not significant. CONCLUSION: Our results indicate that folates supplementation is useful for BD patients with Hhcys.

[Cutaneous manifestations as the initial presentation of Wegener's granulomatosis]. / Atteintes cutanées révélatrices d'une granulomatose de Wegener.

INTRODUCTION: Wegener's granulomatosis is a rare systemic vasculitis, characterized by involvement of the upper airways, lungs and kidneys; other organs may also be affected. Cutaneous lesions occur frequently during the disease course but seldom as its initial presentation. Digital necrosis and splinter hemorrhages of fingernails are described, but very rarely. CASE: We report the case of a 55-year-old man presenting multisystemic Wegener's granulomatosis with mucosal and cutaneous involvement at initial presentation: tongue and labial ulcers, digital necrosis, splinter hemorrhages of fingernails, and purpura. The PR3-ANCA titer was high. Imaging and the histological findings of both cutaneous and renal biopsies suggest a diagnosis of Wegener's granulomatosis. He was treated with prednisone, cyclophosphamide, and cotrimoxazole. Cutaneous and mucosal symptoms disappeared 6 weeks after treatment began. DISCUSSION: The particularity of this case is the association of four separate cutaneous manifestations of Wegener's granulomatosis - two of them very rare - as the initial presentation of this multisystemic disease.

Protracted superficial Wegener granulomatosis in a child.

Wegener granulomatosis is a rare, chronic, multisystemic vasculitis affecting mainly the upper and lower respiratory tracts together with glomerulonephritis, but the disease may involve any other organ. Protracted superficial form is a rare variant of the disease. We report a case of protracted superficial Wegener granulomatosis in a 16-year-old boy in whom the disease started with recurrent digital ulcers at age 7 years. Later, he developed nodules and papules associated with upper airway involvement and ocular keratitis without lung or renal involvement. C-ANCA was positive. The patient was treated with oral prednisone. Similar cutaneous and mucosal lesions developed during two relapses of the disease without renal or respiratory involvement.

[Ureteral stenosis in Wegener's granulomatosis. Case report]. / Sténose urétérale au cours de la granulomatose de Wegener. Une observation.

INTRODUCTION: Ureteral stenoses in Wegener's granulomatosis are rare. They usually involve the pelvic portion of the ureter and are caused by vasculitic lesions or granulomatous inflammation. CASE: A 38-year-old woman with Wegener's granulomatosis was treated with corticosteroids and monthly intravenous cyclophosphamide pulses. After 4 months, urinary retention developed, accompanied by lumbar pain, associated with protenuria and hematuria, and related to bilateral ureteral stenoses. Treatment by endoscopic dilatation and double J stents led to with clinical and radiological improvement, while the medical treatment continued. CONCLUSION: Hematuria in patients with Wegener's granulomatosis suggests renal involvement, but ureteral stenoses must also be considered when these patients present hematuria or urinary tract infections. Surgery should be reserved for those patients in whom medical treatment is not rapidly effective.

[Leflunomide in the treatment of rheumatoid arthritis]. / Le leflunomide (ARAVA) dans le traitement de la polyarthrite rhumatoide.

The aim of this study was to assess the effect and safety of leflunomide (LEF) in refractory RA and to review the literature on this subject. A one year prospective study was conducted on a group of patients (n:15). Mean duration disease was 6.46 years. Rhumatoid factor was present in 12 cases. Leflunomide was administered at a dos of 20mg/day following a loading dose of 100mg/day for three days. The efficacy of LEF was evaluated on clinical and biological parameters of RA evolutivity at one, 3, 6, 9 and 12 months. Our mean follow up period was about 8 months (2 to 12 months). Good prognostic indicators of disease progression were observed with LEF at one month and later in eleven cases with a good safety. Non serious adverse events were observed with LEF. Our result confirm that LEF may present another therapeutic choice that is efficacious for the long term treatment of refractory RA. Nonetheless, these results must be evaluated on a larger series.

[Benzylthiouracil induced ANCA-positive vasculitis]. / Vascularite à anticorps anticytoplasme de polynucléaires neutrophiles induite par le benzylthio-uracile.

INTRODUCTION: Several cases of vasculitis associated with antineutrophil cytoplasmic antibodies (ANCA) have been reported in patients treated with synthetic anti-thyroid drugs but only 2 cases have incriminated benzylthiouracil. OBSERVATION: A 36 year-old woman, 3 years after treatment with benzylthiouracil, rapidly developed progressive kidney failure, related to a pauci-immune extra-capillary glomerular nephropathy and necrotic vasculitis lesions. The search for p-ANCA was positive with anti-myeloperoxidase specificity. She was treated with corticosteroids and 6 monthly intravenous pulses of cyclophosphamide substituted by azathioprine. Renal failure and proteinuria significantly improved. However the high level of p-ANCA. CONCLUSION: ANCA vascularities are a rare but serious complication of treatment with synthetic thiouracile-type anti-thyroid drugs. The ANCA must be measured when confronted with a systemic manifestation during treatment.

[Hyperprolactinemia in systemic lupus erythematosus. A prospective study of 38 cases]. / L'hyperprolactinemie au cours du lupus erythemateux systemique. Etude prospective à propos de 38 cas.

OBJECTIVE: To study prospectively the serum prolactin concentrations among patients with systemic lupus erythematosus and their possible relationship to disease activity and manifestations. METHODS: Serum prolactin levels were measured by radioimmunoassay in 38 patients with systemic lupus erythematosus and 22 age matched controls. Patients with known secondary causes for hyperprolactinaemia, such as pregnancy, lactation, prolactinoma and taking medications known to induce prolactin secretion, were excluded from the study. Demographic, clinical and laboratory features of the patients were obtained. Patients were divided into two subgroups according to their disease activity. Mean prolactin levels from both groups were compared using student test, and prolactin from patients with systemic lupus erythematosus was correlated with variables of disease activity, including the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). RESULTS: Mean prolactin levels were higher in patients with systemic lupus erythematosus (15.4) than healthy controls (9.83); however, the difference did not reach statistical significance (p=). Hyperprolactinemia was found in 24 patients with systemic lupus erythematosus and 5 controls. The frequency of hyperprolactinaemia in systemic lupus erythematosus group was higher than healthy controls. No significant difference in mean prolactin levels was found between patients with active versus inactive disease (18.9 vs 18.5). CONCLUSION: Hyperprolactinaemia occurred significantly in patients with systemic lupus erythematosus, but did not correlate with disease activity.

[Jaccoud arthropathy and pyrophosphate arthropathy: a rare association]. / Arthropathie de Jaccoud et chondrocalcinose articulaire: une association rare.

Jaccoud's arthropathy (JA) is a chronic deformity affecting hands and feet, which are voluntarily correctable by the patients. JA was usually reported in association with rheumatic fever and systemic lupus erythematosus. We describe an exceptional association between a pyrophosphate arthropathy and JA of the hands. It is a 48-year-old woman, having a 13 years history of polyarthritis involving shoulders, elbows, hips and knees, and 4 years after, a progressive unlar deviation of the fingers of the hands. Calcium pyrophosphate dihydrate crystals were identified in the synovial knee biopsy. Hands x-rays as RMI don't identify erosions and confirmed the JA.

[Cardiac involvement in spondylarthropathies]. / L'atteinte cardiaque au cours des spondylarthropathies.

Cardiac involvement is a real manifestation of spondylarthropathies and include specially aortic regurgitation and conduction troubles. We present a prospective open study of fifty patients with spondylarthropathy (responded to Amor criteria) in order to evaluate the frequency of cardiac involvement, to see its type and if we can evaluate a group of patients able to this complication. We have included forty-four men and six women with a mean age of 38 years. The disease evolve for 8.8 years in mean. Ag HLA B27 was present in 70% of the cases. Thirty patients have ankylosing spondylitis, although twenty have a secondary spondylarthropathy: psoriasic rheumatism (12 cases), inflammatory bowel disease: Crohn's disease (4 cases), RCH (three cases) and Fiessenger le Roy-Reiter syndrome in one case. All the patients have had a cardiac check up with research of clinical cardiac manifestation, thoracic chest, trans-thoracic echographi, Halter rhythmic done in five cases only. Cardiac involvement is found in five cases (10%): aortic regurgitation in 3 cases (6%) and mitral regurgitation in 2 cases (4%). These valvular disease are well tolerated.

[TNF alfa modulators in the treatment of rheumatoid arthritis]. / Les modulateurs du TNFalpha dans le traitement de la polyarthrite rhumatoide.

Current slow-acting anti-rheumatic drugs available at now for rheumatoid arthritis fail in majority of cases and have an inconstant chondro-protective effect. Improvements in our knowledge of its pathogenesis and advances in molecular biology have made possible to develop selective immunotherapy approaches. Tumor necrosis factor alfa (TNF alfa) is an important inflammatory mediator that play a crucial role in rheumatoid arthritis. This studies summarizes clinical essays that evaluate beneficial effects and tolerance of anti TNF alfa antibodies. This study showed the clinical, biological and radiological efficacy of these therapeutic agents. But some doubts persist concerning their long term side effects particularly infections, neoplasm or auto immune ones. High price of this treatment should evaluate report cost benefice to appreciate the better utilisation of these drugs.

[Radiologic progression of rheumatoid arthritis lesions treated with methotrexate]. / La progression des lesions radiologiques au cours de la polyarthrite rhumatoïde sous méthotrexate.

Methotrexate is the treatment of reference in rheumatoid arthritis (RA) because it has proved effective in this pathology. Its clinical efficacy is largely admitted but its radiological efficacy is still in certain. The other aim is to look for other clinical and radiological indices that influence these score evolution in patients treated by Methotrexate. Our study is an open prospective study about thirty RA defined about ACR criterions that don't receive other treatment followed up for 6 months. The methotrexate is administered at least 12 months (12 to 72 months) we evaluate its efficacy by Larsen score and Cohin indices. Remission has been reported in 80% of patients according to Larsen score and in 63.3% of patients according to Cohin indices. Its more efficace if admitted as a first treatment and for at least 12 months in young patients (under 40 years) with an arthritis evolution below 10 years and is at stage 0 or 1 of steinbroker but these data are not statistically significant first for patient age and ancientness of RA.

Autologous hematopoietic stem cell transplantation for mediastinal extramedullary plasmocytoma.

Extramedullary plasmocytoma (EMP) is a rare cell neoplasm most frequently localised in the upper respiratory tract. We report the case of a 43 year-old-man, with an unusual presentation of EMP developing in the mediastinum, two years after a diagnosis of solitary plasmocytoma of the bone which was successfully treated by local irradiation. In this aggressive presentation, we decided to perform an autologous hematopoietic stem cell transplantation. Two months after transplantation, CT scan showed disappearance of the mediastinal mass and immunofixation of the serum was normal. Selected cases of diffuse EMP, could benefit from intensive treatment followed by autologous hematopoietic stem cell transplantation.

[Articular manifestations of adult Still's disease]. / Les manifestations osteoarticulaires dans la maladie de Still de l'adulte.

Adult onset Still's disease is a rare systemic disorder of unknown etiology occuring in young adults. The diagnosis is difficult and based upon Yamaguchi's criteria after exclusion of infectious diseases, hemotologic process or autoimmune diseases. Clinical manifestations are various. Functional prognosis depends essentially on articular involvement. We report a retrospective and multicenter study of 26 cases of adult still's disease collected during 10 years. Arthralgia are constant and arthritis are observed in third of the cases. Radiologic joint alterations are found in five cases. A literature review was done with emphasis on clinical and radiological characteristics of articular manifestations.

[MRI findings in pituitary-hypothalamic axis Langerhans cell histiocytosis]. / Apport de l'IRM dans le diagnostic de l'histiocytose langerhansienne hypothalamo-pituitaire.

Pituitary-hypothalamic axis Langerhans cell histiocytosis is an uncommon entity. It is a rare disease in adults. The CT and MR study provides us the best anatomo-topographic evaluation and determine the precise size of the lesion which are necessary to the treatment. We report a case of hypothalamic involvement by Langerhans cell histiocytosis accompanied by lesions in bone affecting a 31-year-old woman. The clinical, histiotological and CT/MR findings of histiocytosis X are described in this article.