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[Screening for breast cancer].

On the "why", "whom" and "how" of breast screening for carcinoma, the following answers can be provided: Why? As there is no primary prevention, secondary prevention by early diagnosis is the only way to reduce breast cancer mortality. On the other hand, breast cancers discovered by screening can be conservatively treated more often than when they become symptomatic; this is especially important in young patients. For whom? Every woman over the age of 35-40 should be accepted for breast cancer screening. In countries such as Switzerland it is unthinkable to impose screening or even to send personal invitations for screening to the population. Only repeated information through newspapers, TV and conferences will induce women to come for screening. The costs would be paid for by the patient, as medical insurances do not cover this type of preventive medicine. How? Only screening through mammography with or without breast palpation, performed by paramedical personnel, can be considered, because of the cost. It should be done outside the senologic consultation setup for symptomatic patients where a doctor is in charge of the clinical consultation. As Doctor Van der Linde said at the end of his talk at the last Convention of the Swiss Senology Society in Lausanne, pilot projects for breast screening in Switzerland should be started. The Swiss Cancer Society has lately created a commission for early detection of breast cancer to study ways of launching a project.

Adult↗

Should you clone your dog? An animal rights perspective on somacloning.

This paper use the Missyplicity Project's detailed Code of Bioethics as a starting point for discussion of animal rights perspectives on cloning. Although funded by a couple in order to clone their pet dog, the project has more important collateral goals and forms part of a general line of research, that, if successful, promises enormous clinical benefits to humans. A particular type of animal rights perspective is described and used to evaluate this project. This perspective accepts a 'principle of axiological anthropocentrism' (PAA), according to which only human beings have certain interests, or a kind of value, which is of pre-eminent moral significance. The best-known animal rights views (those of Singer and Regan) are shown to be consistent with the PAA. This perspective also denies that potential characteristics qualify their possessors for the same type of moral respect as actualized characteristics. The balancing of potential benefits against risks to research subjects is discussed and it is concluded that, from the particular ethical perspective adopted in this paper, cloning research of this general type is not particularly problematic; and, given its stringent Code of Bioethics, only an abolitionist perspective could condemn the Missyplicity Project in particular.

Animal Experimentation↗

Twinning project: Israel and Georgia--the birth of a diabetes-in-pregnancy centre in Georgia.

AIMS: To determine the effectiveness of a joint Israeli-Georgian twinning project aimed at introducing modern methods of perinatal care to Georgian women with pregestational diabetes mellitus. METHODS: A Diabetes-in-Pregnancy Centre was established in Georgia (in the former USSR). Thirty-two women with Type 1 diabetes mellitus participated in the first stage of the study (January 1997-June 1998). All were maintained under strict metabolic surveillance starting at least three months prior to conception and were given organized instruction in methods of self-monitoring of glucose levels, insulin dose adjustment, dietary management and close fetal surveillance throughout pregnancy. A second stage of the project was started in January 1998 and aimed at the diagnosis of gestational diabetes mellitus (GDM). RESULTS: Of the 32 women, 20 had had a total of 44 prior pregnancies without proper perinatal care (1990-96); only five (11.3%) ended in the birth of a healthy infant. On entry to the study, all 32 patients had unsatisfactory metabolic indices. HbA1c levels decreased significantly from the preconception period (P<0.001) and were maintained at the lower level throughout pregnancy; insulin doses decreased significantly until the third trimester (P<0.01) and then increased (P<0.001). Since January 1997, 21 women have become pregnant. Eighteen have given birth, 12 (67%) by Caesarean section and six (33%) by vaginal delivery. Gestational age at birth was 36-39 weeks, and birth weight ranged from 2300 to 4100 g. The only neonatal complications were mild respiratory distress syndrome and hypoglycaemia. There were no significant maternal complications in the 236 women screened, eight were diagnosed as having GDM and 12 impaired glucose tolerance. They were actively managed to a successful outcome. CONCLUSIONS: The establishment of the Diabetes-in-Pregnancy Centre in the Republic of Georgia has significantly reduced the prior high pre-programme perinatal morbidity and mortality as well as the incidence of maternal complications in pre-GDM as well as in GDM.

Adult↗

A model for type II collagen fibrils: distinctive D-band patterns in native and reconstituted fibrils compared with sequence data for helix and telopeptide domains.

The periodical D-band pattern is generally considered a unique ultrastructural feature shared by all fibril-forming collagens, which correlates with the intrafibril, paracrystalline array of tropocollagen monomers. Distinct band patterns have been reported, however, for collagen stained long-spacing (SLS) crystallites of genetic types I, II, and III. Moreover, D-band patterns of negatively stained, native type II collagen fibrils were found to be not identical to those of type I in our previous research. Because of (a) these distinctive features, (b) tropocollagen heterotrimeric conditions (type I) vs homotrimeric conditions (type II), and (c) different lengths and poor homology between extrahelical telopeptides, the molecular array or telopeptide conformation within the extensively studied type I collagen fibrils could be not the same as those in the very much less intensively studied type II collagen fibrils. In this investigation, a distinctive positive-staining D-band pattern was found for type II collagen fibrils obtained from human cartilages. A fibril model was developed by analyzing actual D-band patterns, and matching them against simulated patterns based on the primary structure of extrahelical and helical domains in human type II tropocollagen. In particular, a more prominent b(1) band was apparent in native type II collagen fibrils than in type I. This distinctive feature was also observed for native-type collagen fibrils reconstituted from purified type II collagen, i.e., free from associated minor type XI collagen. On modeling possible monomer arrays, the best fit between microdensitograms and simulation traces was found for 234 amino acid staggering, as is also the case for type I collagen fibrils. On comparing this model with an analogous one for type I collagen fibrils, there was a higher intraband distribution of charged residues for band b(1), consistent with the higher electrondensity observed for this band in type II collagen fibrils. N- and C-telopeptide displacement in the model corresponded to D-locations of a c(2) subband, which we named c(2.0), and band a(3), respectively. In simulation profiles, c(2.0) -like and a(3) -like peaks mimicked the corresponding peaks in microdensitograms when molecular reversals were adopted at positions 10N-12N, 12C-14C, and 17C-19C for N- and C-telopeptides. Hydrophobic interactions and algorithmic predictions of protein secondary structure, according to Chou and Fasman and Rost and Sander criteria, were consistent with these conformational models, and suggest that an additional molecular reversal may occur at positions 3N-5N. These telopeptide "S-fold" conformations, interpreted as axial projections of tridimensional conformation, may represent starting points for further investigation into the still unresolved tridimensional conformation of telopeptides in monomers arrayed within type II collagen fibrils.

Amino Acid Sequence↗

Retinal ganglion cell death during optic nerve regeneration in the frog Hyla moorei.

In the frog Hyla moorei we have estimated there to be between approximately 450,000 and 750,000 cells in the retinal ganglion cell layer. Optic axon counts and retrograde transport of horseradish peroxidase (HRP) indicated that 72-76% of these were ganglion cells. Cells of this type were distributed as a temporally situated area centralis within a horizontal visual streak. Cell and optic axon counts showed that there was an approximately 40% loss of ganglion cells during optic nerve regeneration. Ganglion cells appeared chromatolysed by 6-8 days after an extracranial nerve crush but there was no indication of cell death until 15 days. By this stage anterograde transport of HRP indicated that axons had reached the chiasma. Death was first seen in the area centralis, extended along the streak, and finally was observed in the periphery by 65 days; cell counts demonstrated that at this time the wave of death was almost complete. We have previously shown by electrophysiological visual mapping (Humphrey and Beazley, '82) and confirmed in this study that visuotectal projections were retinotopically organized during regeneration. Multiunit receptive fields were initially large but progressively refined starting in nasal field (temporal retina) to restore a normal projection. The similar sequences whereby the visuotectal projection became refined and death took place in the retinal ganglion cell layer suggested that death may be related to a process of organization within the regenerating projection. In normal animals primary visual pathways revealed by anterograde transport of HRP were essentially similar to those of Rana pipiens and R. esculenta. Regenerating axons generally remained within optic pathways. Exceptions were a retinoretinal projection which was not completely withdrawn even after 1,028 days and a direct projection to the ipsilateral tectum via an inappropriate part of the optic tract.

Animals↗

The child's route into reading and what can go wrong.

Two strands of linguistic development critically important for successful reading acquisition are outlined. One of these ontogenetic roots concerns phonological development and projects onto word decoding. The other root concerns the development of vocabulary and syntax projecting onto reading comprehension. Language development starts very early in infancy when the child learns to categorize the speech sounds according to the pattern typical of the mother tongue. Equipped with these sound categories the child is ready to learn to understand and to use new words. The precise phonological representation of words will facilitate the important development of phonological awareness. The paper reviews some longitudinal research and training studies indicating the causal direction of the relation between phonological awareness and reading. Preventive implications are pointed out. The preventive power of the second strand of development is discussed with reference to vocabulary exposure in different social environments and to informal early literacy socialization. In particular, the benefits of the prototypical situation of reading aloud to children are discussed. Finally, the complexity of the causal relationships between different aspects of early language development and later reading is pointed out.

Awareness↗

Evaluation of reproducibility of solid-phase gastric emptying in healthy subjects.

Radionuclide gastric emptying studies are performed as a matter of clinical routine. Our aim was to evaluate the inter- and intra-individual variability and the reproducibility of gastric emptying studies in healthy young male volunteers using a single solid-phase, standard meal. The meal consisted of a pancake (500 KJ) tagged with technetium 99m sulphur colloid and no additional liquid. Continuous acquisitions of gastric activity in anterior projection were taken during 90 min, starting from the onset of the meal. Gastric emptying was evaluated three times in a 3-week period. Five different parameters were evaluated. Our results show that there is important inter- and intra-individual variability in normal volunteers. In spite of this variability, no significant difference between the different series of gastric emptying studies was observed.

Adult↗

[Integrated navigation. Preclinical evaluation and initial clinical experience].

BACKGROUND: Computer navigation systems have increasingly become part of the surgical routine due to the improvements of intraoperative visualization procedures. Because of limited space in the operating room and insufficient workflow, the project of integrated navigation had been started. METHODS: As the first step, the navigation system VectorVision2 and the second-generation fluoroscopic C-arm system Orbic 3D were integrated into one common trolley. In an experimental study the integrated navigation system was used to drill 160 pedicle screws. Afterwards the system was clinically evaluated in 11 surgical procedures. RESULTS: During the whole experimental study the system could be used for all 160 drilling procedures without any technical faults, causing a failure rate of 4.2%. For clinical evaluation the integrated navigation system was used in seven patients with navigated dorsal spine instrumentation, in three cases sacroiliac screws were placed, and in one case supra-acetabular screw osteosynthesis was performed for an acetabular fracture. In all cases the positioning of the screws was correct and no system failure occurred. CONCLUSIONS: The combination of the navigation system and the C-arm system in one common trolley is a major improvement of the surgical workflow. In the experimental study and the clinical trials the system worked extremely reliably and with high precision.

Acetabulum↗

Developmental dynamics of the bronchial (airway) and air sac systems of the avian respiratory system from day 3 to day 26 of life: a scanning electron microscopic study of the domestic fowl, Gallus gallus variant domesticus.

The lung buds were first conspicuous on day 3 of embryogenesis. They fused on day 4 and the common growth divided into left and right primordial lungs on day 5. Progressively, the lungs elongated, diverged, and advanced towards the respective dorsolateral aspects of the body wall, reaching their definitive topographical locations in the coelomic cavity on day 6. On day 7, they rotated, attached onto the ribs, gradually started to slide into them, and were deeply inserted by day 8. The primary bronchus (PB) first appeared as a solid cord of epithelial cells (day 4) that successively canalized as it invaded the surrounding mesenchyme, extending along the proximal-distal axis of the lung. From day 8, the secondary bronchi (SB) begun to sprout from the PB in a craniocaudal sequence. On day 9, the parabronchi (PR) started to bud from the SB, projecting into the adjacent mesenchyme. They commenced to canalize on day 10 and greatly increased in length, number, and diameter. By day 13, the PR had anastomosed profusely and totally masked the SB. The luminal surface of the PR was lined by a columnar epithelium from which the atria (day 15), infundibulae (day 16), and air capillaries (ACs) (day 18) developed. At hatching (day 21), the ACs were well developed and had anastomosed profusely with the blood capillaries. Of the air sacs (ASs), the abdominal ones appeared earliest (day 5) followed by the cervical ones on day 6. In quick succession, the other ASs were well formed by day 10. After hatching, no further consequential structures formed: only shifts in topographical locations and an increase in size and number occurred. Morphogenetically, the avian respiratory system differs from the mammalian one in certain key aspects: besides the ASs that are unique to it, the lung is exceptionally complex in structure and is essentially mature at the end of the embryonic life.

Air Sacs↗

Support group programme for relatives of terminally ill cancer patients.

GOALS: In order to improve the support for family of terminally ill patients who cared for a dying relative at home, a project with a group programme was started. This article is an evaluation of the programme. The aims of this study were to describe the opinions of participants in a support group programme about the programme and how they felt they had benefited from it. PATIENTS AND METHODS: All subjects (n=39) who completed the programme answered five open-ended questions, and 12 of them were interviewed in semi-structured interviews that were analysed using the phenomenographic method. RESULTS: Three main categories were identified in the interviews: (1) Practical condition and external circumstance--which condition had to be met for participation in the programme. (2) Group effects--the subjects felt that the programme was helpful in several respects, they perceived the programme being an important complement to the palliative home care, they benefited from mutual experiences shared among group members, the programme was also beneficial to the patients and was perceived to have had a health-promoting effect on the relatives. (3) The disease--the issue of how much the patients disease affecting the relatives situation were raised in the groups. CONCLUSION: The results showed the value of the programme for relatives of terminally ill patients nursed in their home. The subjects emphasised the importance of the opportunity to meet people who are in a similar situation.

Adult↗

Identification of the chromosome 12 translocation breakpoint region of a pleomorphic salivary gland adenoma with t(1;12)(p22;q15) as the sole cytogenetic abnormality.

Cell line Ad-312/SV40, which was derived from a primary pleomorphic salivary gland adenoma with t(1;12)(p22;q15), was used in fluorescence in situ hybridization (FISH) analysis to characterize its translocation breakpoint region on chromosome 12. Results of previous studies have indicated that the chromosome 12 breakpoint in Ad-312/SV40 is located proximally to locus D12S8 and distally to the CHOP gene. We here describe two partially overlapping yeast artificial chromosome (YAC) clones, Y4854 (500 kbp) and Y9091 (460 kbp), which we isolated in the context of a chromosome walking project with D12S8 and CHOP as starting points. We present a composite long-range restriction map encompassing the inserts of these two YAC clones and show by FISH analysis that both YACs span the chromosome 12 breakpoint as present in Ad-312/SV40 cells. Subsequently, we have isolated cosmid clones corresponding to various sequence-tagged sites (STSs) mapping within the inserts of these YAC clones. These included cRM51, cRM69, cRM85, cRM90, cRM91, cRM110, and cRM111. In FISH studies, cosmid clones cRM85, cRM90, and cRM111 appeared to map distally to the chromosome 12 breakpoint, whereas cosmid clones cRM51, cRM69, cRM91, and cRM110 were found to map proximally to it. These results assign the chromosome 12 breakpoint in Ad-312/SV40 to a DNA region of less than 165 kbp. FISH evaluation of the chromosome 12 breakpoints in five other pleomorphic salivary gland adenoma cell lines indicated that these are located proximally to the one in Ad-312/SV40, at a distance of more than 0.9 Mbp from STS RM91. These results, while pinpointing a potentially critical region on chromosome 12, also provide evidence for the possible involvement of 12q13-q15 sequences located elsewhere.

Adenoma, Pleomorphic↗

Computer-CT planning of the electron boost in definitive breast irradiation.

Treatment planning of the electron boost in breast irradiation at this institution is performed by using information from CT scanning and from surgical clips used to define the tumor bed. A refinement of this technique, taking into account the surgical axis of approach, using computer-CT planning is now implemented. The location of the scar and the clips are digitized using a computer to define the tumor bed dimensions. With 3-D computer software a line, simulating the surgical axis and the central ray of the electron beam, is drawn between the deepest clip and the surgical scar. This beam's eye view along the surgical axis is projected onto a screen as a starting point. Appropriate gantry angle, treatment table position, beam energy, and precise shaping of the electron field borders with a 2 cm margin around the clips and the scar are determined. Simulation films comparing clinically set-up fields and computer-CT planned fields were reviewed. In only 5 of 17 patients did the clinically set-up field have adequate inclusion of the tumor bed within the treatment volume. Computer-CT planned fields ensured adequate inclusion of the tumor bed in all, including the remaining 12. In 7 patients obvious increased sparing of normal breast tissue was seen with computer-CT planned fields. This technique enables accurate placement of a shaped electron field and further refinement of electron boost treatment planning. This is especially true in situations in which the tumor bed is located at a site distant from the lumpectomy scar rather than directly beneath it and in cases where the tumor bed lies deep within the breast.

Breast Neoplasms↗

Insights in metabolism and toxin production from the complete genome sequence of Clostridium tetani.

The decryption of prokaryotic genome sequences progresses rapidly and provides the scientific community with an enormous amount of information. Clostridial genome sequencing projects have been finished only recently, starting with the genome of the solvent-producing Clostridium acetobutylicum in 2001. A lot of attention has been devoted to the genomes of pathogenic clostridia. In 2002, the genome sequence of C. perfringens, the causative agent of gas gangrene, has been released. Currently in the finishing stage and prior to publication are the genomes of the foodborne botulism-causing C. botulinum and of C. difficile, the causative agent of a wide spectrum of clinical manifestations such as antibiotic-associated diarrhea. Our team sequenced the genome of neuropathogenic C. tetani, a Gram-positive spore-forming bacterium predominantly found in the soil. In deep wound infections it occasionally causes spastic paralysis in humans and vertebrate animals, known as tetanus disease, by the secretion of potent neurotoxin, designated tetanus toxin. The toxin blocks the release of neurotransmitters from presynaptic membranes of interneurons of the spinal cord and the brainstem, thus preventing muscle relaxation. Fortunately, this disease is successfully controlled through immunization with tetanus toxoid, a formaldehyde-treated tetanus toxin, but nevertheless, an estimated 400,000 cases still occur each year, mainly of neonatal tetanus. The World Health Organization has stated that neonatal tetanus is the second leading cause of death from vaccine preventable diseases among children worldwide. This minireview focuses on an analysis of the genome sequence of C. tetani E88, a vaccine production strain, which is a toxigenic non-sporulating variant of strain Massachusetts. The genome consists of a 2,799,250 bp chromosome encoding 2618 open reading frames. The tetanus toxin is encoded on a 74,082 kb plasmid, containing 61 genes. Additional virulence-related factors as well as an insight into the metabolic strategy of C. tetani with regard to its pathogenic phenotype will be presented. The information from other clostridial genomes by means of comparative analysis will also be explored.

Journal Article↗

V meeting of the European forum on antiphospholipid antibodies.

The "V Meeting of the European Forum on Antiphospholipid Antibodies" was organized in Barcelona, Catalonia, Spain, on December 2-3, 2005. This biannual meeting becomes a real forum for the interchange of information on current research on the field antiphospholipid antibodies and the antiphospholipid syndrome, as well as a starting point for many new research projects. About 170 physicians and researchers from a great variety of medical specialities (internists, rheumatologists, hematologists, obstetricians, pediatricians, neurologists, cardiologists, immunologists, and biologists, among others) coming from 20 European countries attended the sessions. This report summarizes the main studies and new research projects presented during this Forum Meeting.

Animals↗

On development of medical informatics education via European cooperation.

In this paper, we show different activities of the European Center for Medical Informatics, Statistics and Epidemiology (EuroMISE Center) of Charles University and Academy of Sciences in the field of medical informatics, statistics and epidemiology education and training. The development of these activities started within the TEMPUS-PHARE project in 1993 and they are continuing with the support of another project, particularly the IT EDUCTRA (Information Technologies Education and Training) (Fourth Framework Programme) project. New approaches using the Internet as well as newly developed programmes are described.

Czech Republic↗

An automated system for the analysis of G protein-coupled receptor transmembrane binding pockets: alignment, receptor-based pharmacophores, and their application.

G protein-coupled receptors (GPCRs) share a common architecture consisting of seven transmembrane (TM) domains. Various lines of evidence suggest that this fold provides a generic binding pocket within the TM region for hosting agonists, antagonists, and allosteric modulators. Here, a comprehensive and automated method allowing fast analysis and comparison of these putative binding pockets across the entire GPCR family is presented. The method relies on a robust alignment algorithm based on conservation indices, focusing on pharmacophore-like relationships between amino acids. Analysis of conservation patterns across the GPCR family and alignment to the rhodopsin X-ray structure allows the extraction of the amino acids lining the TM binding pocket in a so-called ligand binding pocket vector (LPV). In a second step, LPVs are translated to simple 3D receptor pharmacophore models, where each amino acid is represented by a single spherical pharmacophore feature and all atomic detail is omitted. Applications of the method include the assessment of selectivity issues, support of mutagenesis studies, and the derivation of rules for focused screening to identify chemical starting points in early drug discovery projects. Because of the coarseness of this 3D receptor pharmacophore model, however, meaningful scoring and ranking procedures of large sets of molecules are not justified. The LPV analysis of the trace amine-associated receptor family and its experimental validation is discussed as an example. The value of the 3D receptor model is demonstrated for a class C GPCR family, the metabotropic glutamate receptors.

Amino Acid Sequence↗

The value of marginality in a medical school: general practice and curriculum change.

OBJECTIVE: To report the process of introduction, development and sustenance of a curriculum for a department of general practice in the context of changing curricula required by the General Medical Council. SETTING AND CONTEXT: Tayside Centre for General Practice, the Department of General Practice within Dundee University Medical School. METHODS: Use of action research methodology common in educational and sociological research. Action research utilizes a range of data collection techniques which allow the participants in the research full opportunities to reflect on the data as it emerges and make developments accordingly. ANALYSIS: This took place as part of the process of the 5-year project. The analysis used as its starting point the sociological theory of the social construction of power within institutions. It offers the thesis that marginality seems to be a prerequisite in confronting institutional conservatism. CONCLUSIONS: Use of an action research model facilitated more effective change by providing a supportive atmosphere in which to tackle changes. The marginal status of the general practice group in relation to the medical school allowed creative negotiation of alliances within the medical school. Other groups within the medical school who are introducing new curricula can learn from this report.

Curriculum↗

Selective regeneration of the neuromuscular connections in the pteropod mollusc Clione limacina.

In the pteropod mollusc Clione limacina, two different groups of motoneurons innervate two physiologically identical wing muscles (dorsal and ventral). When motoneuron axons are crushed in the nerve of whole animals regeneration starts. In its course motoneurons initially project to both the correct and incorrect muscles. Then incorrect connections and neurites are eliminated and the original innervation is restored. Here we investigated neuromuscular regeneration when one of the muscles was removed or the muscle size was reduced. Motoneurons formed both correct and incorrect connections not only in vitro when the pedal ganglion was attached to only one of two wing muscles, but also in whole-animal 'no choice' experiments when only one muscle was available for reinnervation. In these experiments incorrect connections were stable and were not eliminated at the later stages, as happened in experiments in which both muscles were accessible. In whole-animal experiments with reduced size of the muscles, a normal pattern of regeneration was conserved although not all incorrect connections were eliminated. Thus, in the course of regeneration: (i) locomotor motoneurons make connections with both correct and incorrect muscles; (ii) if for some group of motoneurons the correct targets are unavailable, the incorrect connections survive and become stable; (iii) if both groups of motoneurons have a choice between the correct and incorrect targets, initial mixed innervation is replaced by purely correct innervation; (iv) elimination of incorrect synapses could be a result of the competition between correct and incorrect synapses of the same neuron.

Action Potentials↗