Genetic mapping of a major susceptibility locus for juvenile myoclonic epilepsy on chromosome 15q

The epilepsies are a group of disorders characterised by recurrent seizures caused by episodes of abnormal neuronal hyperexcitability involving the brain. Up to 60 million people are affected worldwide and genetic factors may contribute to the aetiology in up to 40% of patients. The most common human genetic epilepsies display a complex pattern of inheritance. These are categorised as idiopathic in the absence of detectable structural or metabolic abnormalities. Juvenile myoclonic epilepsy (JME) is a distinctive and common variety of familial idiopathic generalised epilepsy (IGE) with a prevalence of 0.5-1.0 per 1000 and a ratio of sibling risk to population prevalence (lambda(s)) of 42. The molecular genetic basis of these familial idiopathic epilepsies is entirely unknown, but a mutation in the gene CHRNA4, encoding the alpha4 subunit of the neuronal nicotinic acetylcholine receptor (nAChR), was recently identified in a rare Mendelian variety of idiopathic epilepsy. Chromosomal regions harbouring genes for nAChR subunits were therefore tested for linkage to the JME trait in 34 pedigrees. Significant evidence for linkage with heterogeneity was found to polymorphic loci encompassing the region in which the gene encoding the alpha7 subunit of nAChR (CHRNA7) maps on chromosome 15q14 (HLOD = 4.4 at alpha = 0.65; Z(all) = 2.94, P = 0.0005). This major locus contributes to genetic susceptibility to JME in a majority of the families studied.     

Induced abortion in a Swiss canton from 1990 to 1993: implications for epidemiological surveillance

BACKGROUND: To describe abortion utilization in the Canton of Vaud (Switzerland) and to identify desirable changes in the data collection system to improve the epidemiologic monitoring METHODS: Retrospective survey of the 5600 abortion requests to the Canton Health Authority for resident women between 1990 and 1993. RESULTS: Nine women out of 1000 residents requested an abortion, but the abortion rate was higher among women of foreign origin compared to Swiss women (17/1000 vs. 6/1000, p < 0.0001). The proportion of terminated recognized conceptions was 127/1000, and the ratio of IVG to livebirths was 0.18. The abortion rate was lower during adolescence (6/1000) or after 40 years of age (1.8/1000), whereas the proportion of terminated conceptions was highest at these ages (527/1000 and 312/1000). Abortion utilization in Canton of Vaud is among the lowest. CONCLUSIONS: Although these indicators do reflect a satisfactory accessibility and use of family planning services, improvements could be made. A better knowledge of the causes (motives, contraceptive method, reproductive history) and of the consequences of abortion (psycho-social implications, medical complications) would allow to design more focused prevention strategies and to fit health services to current needs. Updating the 1942 Swiss legislation is also desirable.     

Use of the polymerase chain reaction in the diagnosis of leprosy

A case is described in which a pericardial branch of a nongrafted left internal mammary artery communicated directly with the distal left anterior descending artery, following saphenous vein bypass grafting. This type of collateralization following coronary artery bypass surgery seems to be very rare, and perhaps could protect the myocardium from severe ischemia.     

Characterizing replication intermediates in the amplified CHO dihydrofolate reductase domain by two novel gel electrophoretic techniques

Using neutral/neutral and neutral/alkaline two-dimensional (2-D) gel techniques, we previously obtained evidence that initiation can occur at any of a large number of sites distributed throughout a broad initiation zone in the dihydrofolate reductase (DHFR) domain of Chinese hamster ovary (CHO) cells. However, other techniques have suggested a much more circumscribed mode of initiation in this locus. This dichotomy has raised the issue whether the patterns of replicating DNA on 2-D gels have been misinterpreted and, in some cases, may represent such noncanonical replication intermediates as broken bubbles or microbubbles. In an accompanying study (R. F. Kalejta and J. L. Hamlin, Mol. Cell. Biol. 16:4915-4922, 1996), we have shown that broken bubbles migrate to unique positions in three different gel systems and therefore are not likely to be confused with classic replication intermediates. Here, we have applied a broken bubble assay developed from that study to an analysis of the amplified DHFR locus in CHO cells. This assay gives information about the number and positions of initiation sites within a fragment. In addition, we have analyzed the DHFR locus by a novel stop-and-go-alkaline gel technique that measures the size of nascent strands at all positions along each arc in a neutral/neutral 2-D gel. Results of these analyses support the view that the 2-D gel patterns previously assigned to classic, intact replication bubbles and single-forked structures indeed correspond to these entities. Furthermore, potential nascent-strand start sites appear to be distributed at very frequent intervals along the template in the intergenic region in the DHFR domain.     

Using Multimedia to Support Cooperative Editing

By Cooperative Editing we mean the coordinated manipulation of information by a group of authors. During the editing process the (co-)authors need to communicate their ideas, drafts and constraints (remotely or face-to-face) until a final version of the information is achieved. For the different phases of this process - discussion of ideas, editing, cross-checking - different media or media integration are adequate. Furthermore, analysing the transition from individual work to group work, within different human activities, two pitfalls are often detected if computer support is considered: a) technological communication difficulties, especially if the group is remotely located on heterogeneous hardware, associated with a fall in productivity and frequent social inadequacies of the group's computer support; b) the lack of integrated media processing tools available for group editing. In order to solve these problems, we suggest that Multimedia can be applied in two ways: to effectively support the necessary group communication links; and to enhance the expressiveness of the information edited. To test this statement we have been conceptualising and implementing a prototype system. Most of the techniques involved can be used in other tools that need multimedia capabilities or that support other specific types of group activities. The innovative aspects of the work are the use of multimedia techniques to support demanding applications, possibly on cross-platforms, and the integration of several concepts to support cooperation.     

Morphological and functional polymorphism within clonal thyroid nodules

Thirty-nine thyroid nodules, removed because of recent growth, were analyzed morphologically by serial histological sections for the classical histomorphological hallmarks of follicular cell replication and for immunohistochemically demonstrable overexpression of the growth-associated ras-gene product p21ras. Clonal analysis was performed using the highly informative probe M27 beta that detects polymorphisms on the locus DXS255 of the X-chromosome. Twenty-four nodules were of clonal and 15 nodules were of poly-clonal origin. Only 3 out of the 24 clonal nodules were histomorphologically uniform. In all others, the structural hallmarks of active growth and the P21ras growth-marker expression were remarkably heterogeneous throughout the tumors. There were no histomorphological characteristics distinguishing these clonal tumors from polyclonal nodules. Even if a clonal thyroid tumor may be originally homogeneous in respect to the parameters studied here, mechanisms must exist that create wide heterogeneity of growth and of morphogenetic potential among the individual follicular cells during further expansion of the nodule. Thus, clonal nodules are much more common in nodular goiters than hitherto assumed on grounds of the classical morphological criteria. The diagnosis of a true monoclonal nodule can no longer rely on morphological and functional criteria alone but requires molecular or cytogenetic analysis of clonality.     

Cooperative Hypermedia Editing with CoMEdiA

CoMEdiA is a groupware tool which enables co-authors to cooperatively produce hypermedia documents.CoMEdiA allows co-authors to communicate their ideas,drafts,guidelines,constraints and annotations to other co-authors.In uses a mix of communication patterns,media and document organization to enable co-authors to keep on exchanging information(remotely or face-to-face),improving passages and modifying notes until a final document is achieved.We did not concentrate on th depth but on the breath of the features.Our efforts were on integrating and corrdinating concepts from collaboration,multimedia and hyper organization rather than on making a specialized system in any of them.We began with the text medium and are now including bitmaps and raster images.Later sound and video will also be integrated.In this paper we describe and sustain the available capacites.     

Design flaw can convert commercially available continuous syringe pumps to intermittent bolus injectors

OBJECTIVE: To investigate if unexpected behaviour of neonatal and paediatric patients connected to syringe pumps could be explained by transient elevation of these devices. DESIGN: Five different commercially available syringe-pumps were set at an infusion rate of 1 ml/h and then subjected to a vertical displacement manoeuvre (height 1 m). The actual delivered infusion volumes in association with the displacement manoeuvre were measured by a high precision weight scale connected to a computer. SETTING: A medical technology laboratory in a university hospital. MEASUREMENTS AND RESULTS: Elevation of the devices resulted in a rapid bolus injection of 0.19-2.28 ml. Returning the devices to their original positions resulted in an aspiration into the system of 0.06-0.34 ml. The times both for bolus injection and for aspiration into the system were less than 1 min in all cases. The updown manoeuvre was followed by a period with zero infusion ranging from 8 to 105 min. CONCLUSIONS: Design flaws in the construction of syringe pumps can expose patients to substantial danger following vertical displacement if potent drugs are being infused. If potent drugs are infused, care should be taken not to change the vertical position of the syringe pump even for short periods of time. Before buying new equipment, the authors recommend that the delivery characteristics of these devices should not only be tested during ordinary bench testing but should also include the reaction to a vertical displacement manoeuvre.