[Development of a learning game for ophthalmic technicians: "Orthoptist Simulator"]. / Développement d'un jeu sérieux pour la formation des orthoptistes : « orthoptist simulator ¼.

INTRODUCTION: E-learning is a pedagogic approach that relies on the use of electronic media and devices as tools to improve access to training, communication and interaction, facilitating the adoption of knowledge, skills and/or behaviors. Learning games offer a learning and training environment using entertaining elements from video games in a real-life scenario. The objective of this work is the conception of a learning game for training ophthalmic technician students. METHODS: Design of a learning game, in collaboration with iLumens and the Dowino® corporation, allowing the performance of an orthoptic evaluation in a child without ocular pathology. RESULTS: We developed the "Orthoptist Simulator" a learning game that faithfully reproduces an orthoptic box with necessary tools to carry out an orthoptic evaluation with ocular motility examination. The game offers learning, training and self-evaluation modes. It allows the student to evaluate a young patient, take a history and perform the 17 most frequently used orthoptic tests. The student thus creates a report of the results of these tests to be transmitted to the ophthalmologist who requested the workup. CONCLUSIONS: To our knowledge, we have set up the first learning game for the training of future ophthalmic technicians, which is an innovative educational tool and complementary to traditional training. This game could also be used to train ophthalmology residents in ocular motility examination. This new instrument will require future evaluation to determine its real impact on training.

The mannose cap of mycobacterial lipoarabinomannan does not dominate the Mycobacterium-host interaction.

Pathogenic mycobacteria have the ability to persist in phagocytic cells and to suppress the immune system. The glycolipid lipoarabinomannan (LAM), in particular its mannose cap, has been shown to inhibit phagolysosome fusion and to induce immunosuppressive IL-10 production via interaction with the mannose receptor or DC-SIGN. Hence, the current paradigm is that the mannose cap of LAM is a crucial factor in mycobacterial virulence. However, the above studies were performed with purified LAM, never with live bacteria. Here we evaluate the biological properties of capless mutants of Mycobacterium marinum and M. bovis BCG, made by inactivating homologues of Rv1635c. We show that its gene product is an undecaprenyl phosphomannose-dependent mannosyltransferase. Compared with parent strain, capless M. marinum induced slightly less uptake by and slightly more phagolysosome fusion in infected macrophages but this did not lead to decreased survival of the bacteria in vitro, nor in vivo in zebra fish. Loss of caps in M. bovis BCG resulted in a sometimes decreased binding to human dendritic cells or DC-SIGN-transfected Raji cells, but no differences in IL-10 induction were observed. In mice, capless M. bovis BCG did not survive less well in lung, spleen or liver and induced a similar cytokine profile. Our data contradict the current paradigm and demonstrate that mannose-capped LAM does not dominate the Mycobacterium-host interaction.

Autoantibodies in lupus nephritis patients requiring renal transplantation.

The goal of this nested case-control study was to compare autoantibody profiles in systemic lupus erythematosus (SLE) patients with lupus nephritis (LN), lupus nephritis patients requiring renal transplantation (LNTP) and a SLE control group without nephritis (CON). Sera were assayed for a variety of autoantibodies by addressable laser bead immunoassay (ALBIA) and enzyme-linked immunoassay (ELISA) and to dsDNA by Crithidia luciliae assay. The frequency of nucleosome autoantibodies was significantly greater in the LNTP group (79%) compared to the LN (18%) and CON (9%) groups (P < 0.0005). The frequency of other autoantibodies, including anti-dsDNA, did not differ significantly between groups. Among patients with LN, the odds of progressing to renal transplantation was 16-fold higher (OR 16.5 [95% CI 2.5, 125.7], P = 0.0005) in patients testing positive for anti-nucleosome antibodies compared to those who tested negative. Furthermore, the level of anti-nucleosome antibodies was significantly ( P < 0.00005) higher in the LNTP group (3.69 +/- 2.79) than the LN (0.51 +/- 0.51) and CON (0.34 +/- 0.44) groups. Review of 48 renal biopsies from 29 patients indicated that there was no difference in renal histological classification among patients with anti-nucleosome antibodies compared to those who tested negative. Our observations suggest that nucleosome autoantibodies are a biomarker for more severe SLE renal disease requiring transplantation.

Differences in response to anaesthetics and analgesics between inbred rat strains.

Differences in response to analgesic and anaesthetic drugs can partly be attributed to variations in the genetic background of experimental animals. This study was carried out to determine differences in the response of inbred rat strains to a selection of analgesics and drugs used in anaesthetic protocols. A cross between the most contrasting strains can then be phenotyped in future studies in order to localize quantitative trait loci (QTLs) involved in analgesic/anaesthetic drug sensitivity. Eight inbred strains (n = 6 rats/strain) were selected for the study: the pigmented ACI, BN and COP strains and the albino F344, LEW, SHR, WAG and WKY strains. Each rat was injected intravenously with two analgesics (buprenorphine 0.05 mg/kg and nalbuphine 1 mg/kg) and three drugs used in anaesthetic protocols (propofol 25 mg/kg, medetomidine 50 microg/kg and ketamine 10 mg/kg), respectively, using a crossover design. Analgesic responses were assessed using an analgesiometric procedure. The sleep time of the rat and, where applicable, the interval between injection and loss of righting reflex were used to determine the anaesthetic response. Six out of eight strains responded significantly different from each other to the analgesic effect of buprenorphine with the ACI strain as hyper-responder. The tail withdrawal latency at 55 degrees C of the F344 and WKY rats using buprenorphine was not significantly different from baseline tail withdrawal latencies. In this study, all strains were non-responsive to the analgesic effects of nalbuphine. The response to all three drugs used in anaesthetic protocols differed significantly among the strains. The F344 and BN strains were relatively resistant to the sedative effects of medetomidine. Use of ketamine was abandoned in the ACI and BN strains when the first two animals of both strains died soon after induction. With all three drugs the sleep time of albino rats was significantly longer compared with that of the pigmented ones. We conclude that the results from this study can be used in future studies where QTLs for the sensitivity to anaesthetic/analgesic drugs are localized.

Among therapy modalities of end-stage renal disease, renal transplantation improves survival in patients with amyloidosis.

The aim of this study was to investigate the results of renal transplantation in amyloidosis patients compared with those on hemodialysis. We compared a group of 25 patients with systemic amyloidosis and end-stage renal disease (ESRD) treated with renal transplantation with a control group of 30 patients with systemic amyloidosis and ESRD treated with hemodialysis. Overall 1-, 2-, and 5-year survival rates were 86.9%, 82.6%, and 78.2%, respectively, for patients, who had renal transplantations versus 60.7%, 50%, and 46.4%, respectively, for patients on hemodialysis treatments (P < .001). Among the control group 15 patients died at 9.4 +/- 7.5 months after starting hemodialysis. Among transplantation group five patients died during follow-up (mean 12.3 +/- 13.6 months); the major cause of death was infection. Only 18 patients experienced recurrences after renal transplantation; their 5-year survival rate was 84.2% versus 50% for patients who had no recurrence (P < .001). Patients with amyloid recurrence also had better long-term survival rates than patients in hemodialysis group (P < .001). In conclusion amyloidotic patients maintained on chronic dialysis have a high mortality rate. Better survival was noted for patients who had renal transplantations despite recurrences. These results encourage transplantation in amyloid renal end-stage disease.

Posttransplant tubulointerstitial nephritis: clinicopathological correlation.

As a cause of graft dysfunction, tubulointerstitial nephritis (TIN) seems to be the third most common pathology after rejection and cyclosporine nephrotoxicity. Among 540 needle biopsies obtained from 280 renal transplant patients between 1996 and 1999, acute TIN was detected in 23 patients (8%). The cause of acute TIN was secondary to bacterial infection in 17 patients and secondary to cytomegalovirus (CMV) infection in three patients. The remaining three cases showed granulomatous pyelonephritis due to Mycobacterium tuberculosis (n = 2) and Candida albicans (n = 1). During follow-up, 13 of 23 patients (56.5%) showed at least one acute rejection episode. The average number of urinary tract infection (UTI) episodes in the 23 patients was 1.4 +/- 07. We observed that the number of UTI episodes showed a significant association with the development of chronic allograft nephropathy (P = .03) and graft loss (P < .01). Twelve patients (52.2%) lost their grafts during 5 years posttransplantation. Only 6 of 17 patients with bacterial TIN lost their graft at a mean time of 52.5 +/- 14 months. But all patients with CMV TIN or granulomatous TIN lost their grafts at a mean time of 31 +/- 3.1 months and 39 +/- 3 months, respectively (P < .05). In conclusion, these results support the pathological role of tubulointerstitial nephritis as a pathway of graft rejection or renal allograft deterioration among recipients after transplantation.

Does colchicine have an antifibrotic effect on development of interstitial fibrosis in renal allografts of recipients with familial Mediterranean fever?

Colchicine, which has been reported to inhibit fibrosis, has been successfully used to treat fibrotic disorders, such as liver cirrhosis, scleroderma, and idiopathic pulmonary fibrosis. We hypothesized that besides its ability to prevent amyloid deposition, colchicine may prevent the development of interstitial fibrosis (IF) in amyloidosis patients who had undergone renal transplantation. We evaluated the influence of colchicine therapy on the development of IF in 25 patients with systemic amyloidosis secondary to familial Mediterranean fever (group 1). Twenty-five nonamyloidotic patients who did not receive colchicine therapy served as controls (group 2). The incidences of recurrence and development of IF in the first, second, and third years after transplantation were evaluated from follow-up allograft biopsies. Only four patients showed amyloid recurrence in their renal allografts. IF developed in 44% (11/25) of group 1 patients and 80% (20/25) of group 2 patients during the 36 months posttransplantation (P < .01). Development of IF in the first, second, and third years posttransplantation was significantly greater among group 2 recipients than group 1 recipients (P < .01). The overall 1-, 2-, and 3-year graft survival rates for group 1 recipients were 96%, 92%, and 80%, and those for group 2 recipients were 96%, 88%, and 60%, respectively. Our results support the thesis that colchicine therapy may help prevent the development of interstitial fibrosis in renal allografts.

Hepatic stellate cells in biopsies from liver allografts with acute rejection.

BACKGROUND: [corrected] Hepatic stellate cells (HSCs) are nonparenchymal elements that play a major role in fibrogenesis due to various pathologies. HSCs are easily activated by certain injuries, which produce contraction and relaxation of HSCs, resulting in hepatic microcirculatory disturbances. The present study sought to analyze the expression of alpha-smooth muscle actin (alpha-SMA) positive HSCs in liver allografts during acute rejection episodes (ARE), determining whether it was related to the pathogenesis of this immune response. MATERIALS AND METHODS: Using immunohistochemistry and a semiquantitative scoring system, the expression of alpha-SMA in HSCs was analyzed in liver allografts with ARE (group 1, n = 64) or without ARE (group 2, n = 20). Normal liver tissue from transplant donors (group 3, n = 53) served as the control materials. RESULTS: Significantly more alpha-SMA positive HSCs were found in group 2 than in the other two groups (P < .05). The minimal difference observed between groups 1 and 3 was not statistically significant. As well, no statistical association was found between expression of alpha-SMA and the clinical parameters of age, gender, etiology of liver failure, donor type (partial or whole), posttransplantation period, and liver function tests. CONCLUSIONS: While these results represent preliminary findings, it may be possible that HSC expression is a protective mechanism during ARE in hepatic allograft patients. If this is true, enhanced expression of this protein may mitigate ARE in liver allograft patients.

Sociodemographic factors and age at natural menopause in Shiraz, Islamic Republic of Iran

With increasing life expectancy, menopause is an increasingly important aspect of women's health. We recorded the age at natural menopause among women in a population-based cross-sectional study in Shiraz, Islamic Republic of Iran, in summer 2000. Interviews with 948 randomly selected menopausal women showed the mean [st and ard deviation] age at menopause was 48.3 [5.3] years [95% CI: 48.0-48.6], median 49 years. The sociodemographic and health behaviour factors that were significantly related to early mean age of menopause were: never married [44.7 years], low income level [47.4 years], low social class [45.8 years], tobacco use [47.9 years] and non-consanguineous husb and [48.1 years]

Expression of receptor protein-tyrosine phosphatase alpha, sigma and LAR during development of the zebrafish embryo.

Receptor protein-tyrosine phosphatases (RPTPs) are key players in Drosophila development. To study the role of RPTPs in vertebrate development, we have cloned zebrafish (zf) RPTPs, including RPTP alpha (RPTPalpha), RPTP sigma (RPTPsigma) and LAR. These three RPTPs are broadly transcribed in early development. At 24h post fertilisation (hpf), all three genes are expressed in the nervous system in partially overlapping patterns. At 3 days post fertilisation zf-RPTPalpha and zf-LAR show similar expression patterns in the central nervous system (CNS), the pharyngeal arches, the pectoral fins and the spinal cord. Interestingly, zf-LAR is uniquely expressed in the neuromast cells, whereas zf-RPTPsigma expression is confined to the central nervous system.

Receptor protein-tyrosine phosphatase signalling in development.

Receptor Protein-Tyrosine Phosphatases (RPTPs) belong to the superfamily of protein-tyrosine phosphatases and have the intrinsic ability to transduce signals across the cell membrane. We are beginning to understand the role of RPTPs in development of invertebrates, due to elegant genetic studies. In contrast, relatively little is known about the role of RPTPs in vertebrate development. Signalling by RPTPs has predominantly been studied in mammalian cell systems, which has led to important insights into potential ligands, into regulation of RPTP activity and into potential RPTP substrates. Here, we will introduce the RPTPs, and discuss the function of the LAR-subfamily of RPTPs. In addition, we focus on the function and signalling of the haematopoietic RPTP, CD45. Finally, we will discuss the structure and function of RPTPalpha, the RPTP that is the subject of our studies.

Pleiotropic effects of zebrafish protein-tyrosine phosphatase-1B on early embryonic development.

Protein tyrosine phosphorylation is an important mechanism of eukaryotic cell signalling which is regulated by protein-tyrosine kinases and protein-tyrosine phosphatases. Here we report the molecular cloning of the first zebrafish protein-tyrosine phosphatase, zf-PTP-1B, the homologue of human PTP-1B. Zf-PTP-1B was catalytically active and localised to the endoplasmic reticulum, like human PTP-1B. Zf-PTP-1B was maternally expressed in zebrafish embryos, and low ubiquitous expression was detected up to day 7 of development. Microinjection of zf-PTP-1B RNA induced pleiotropic, but reproducible developmental defects. Evaluation of the live embryos at 24 h post fertilisation indicated that zf-PTP-1B induced defects in somite formation. The phenotype was dependent on protein-tyrosine phosphatase activity of zf-PTP-1B, since embryos injected with catalytically inactive zf-PTP-1B-C213S developed normally. Co-injection of wild type and inactive zf-PTP-1B led to a rescue of the zf-PTP-1B-induced phenotype, suggesting that zf-PTP-1B-C213S had dominant negative activity. The zf-PTP-1B-induced phenotype suggests that proper tyrosine phosphorylation of key proteins is essential for early development, most notably somitogenesis.

Manual de descenso helitactico

Manual de descenso helitactico y rapell. Equipo general y de anclaje. Equipo individual. Metodos de engachar la soga al eslabon para un deslizamiento desde helicoptero con silla suiza para un hombre derecho. La instalacion de una argolla de acero en un helicoptero UH-1H.Nudos de amarre. Nudos y aparejos

Osteomyelitis of the jaws in pycnodysostosis.

Pycnodysostosis is a rare sclerosing bone disorder in which osteomyelitis of the jaws is a frequent complication. Treatment of osteomyelitis of the jaws in pycnodysostosis is difficult and may lead to large resections. A review of the literature and 3 new cases in which osteomyelitis was successfully treated by a combined surgical and antibiotic approach, are reported.

Serological and clinical evidence of toxoplasmosis on the Upper Leeward Islands.

Toxoplasma infections are common on the Upper Leeward Islands (Saba, St. Maarten and St. Eustatius, Neth. Antilles) as proved by clinical evidence and serological determinations in patients and in healthy people. In schoolchildren an overall positive percentage of 45.5% was found. On St. Eustatius the highest frequency of recent infections was in the youngest age groups, in contrast with findings in the Netherlands and in Germany.

Serological evidence of dengue virus activity in children on the Northern Leeward Islands (Netherlands Antilles).

An arbovirus serologic survey of school children on the Northern Leeward Islands (Saba, St. Eustatius and St. Maarten) using haemagglutination inhibition (HI) detected a high proportion of reactors to dengue types 1,2, and 3. Analysis in relation to age showed an increasing proportion to be positive with increasing age. The results of an all-age survey on St. Eustatius 1970 led to the hypothesis of possible dengue serotype 1 activity on St. Eustatius around 1900, whilst it is thought that dengue type 2 was endemic at other times. In view of the continuous high endemic dengue activity the (re)-appearance of dengue serotype 1 next to type 2 and 3 may be the prelude to the occurrence of the dengue shock syndrome.