HER2 expression in breast cancer primary tumours and corresponding metastases. Original data and literature review

The aim of this study was to evaluate whether the HER2 expression in breast cancer is retained in metastases. The HER2 expression in primary tumours and the corresponding lymph node metastases were evaluated in parallel samples from 47 patients. The HercepTest was used for immunohistochemical analyses of HER2 overexpression in all cases. CISH/FISH was used for analysis of gene amplification in some cases. HER2 overexpression (HER2-scores 2+ or 3+) was found in 55% of both the primary tumours and of the lymph node metastases. There were only small changes in the HER2-scores; six from 1+ to 0 and one from 3+ to 2+ when the metastases were compared to the corresponding primary tumours. However, there were no cases with drastic changes in HER2 expression between the primary tumours and the corresponding lymph node metastases. The literature was reviewed for similar investigations, and it is concluded that breast cancer lymph node metastases generally overexpress HER2 to the same extent as the corresponding primary tumours. This also seems to be the case when distant metastases are considered. It has been noted that not all patients with HER2 overexpression respond to HER2-targeted Trastuzumab treatment. The stability in HER2 expression is encouraging for efforts to develop complementary forms of therapy, for example, therapy with radionuclide-labelled Trastuzumab.     

Maternal anxiety in late pregnancy: effect on fetal movements and fetal heart rate

AIM: To determine whether maternal state and trait anxiety levels affect fetal movements or fetal heart rate (FHR) in the third trimester. SUBJECTS: Forty-one healthy pregnant nulliparous women not on medication and with a singleton pregnancy. STUDY DESIGN: Maternal anxiety was assessed using the Spielberger State- Trait Anxiety Inventory (Form Y) at 36 gestational weeks. The fetuses of the women were examined at 37-40 gestational weeks with ultrasound observation of fetal movements and cardiotocography (CTG). The results of the fetal examinations were compared between women with low and high anxiety scores (low scores being defined as scores below the median and high scores as scores equal to or above the median of the study population), and correlation analyses between anxiety scores and the outcome variables were performed. OUTCOME MEASURES: The presence and duration (expressed as a percentage of the total examination time) of FHR patterns A, B, C, and D, the percentage duration of fetal movements in each FHR pattern, baseline FHR and FHR variability in each FHR pattern. RESULTS: The presence of FHR patterns A, B, C, and D, the duration of FHR patterns A, B, and C, FHR variability in FHR patterns A, B, and C, baseline FHR and the percentage duration of fetal movements in each FHR pattern did not differ between women with low and high state and trait anxiety scores. In fetuses with FHR pattern D, the duration of FHR pattern D increased with increasing maternal trait anxiety scores, (rho=0.88; p=0.008), and FHR variability in FHR pattern D increased with maternal state and trait anxiety scores (r=0.86, p=0.01; r=0.96, p=0.001). CONCLUSION: Maternal anxiety does not seem to affect fetal movements or baseline FHR in late pregnancy, but there is a possible association between maternal anxiety and the duration of FHR pattern D and FHR variability in FHR pattern D.     

Applying phenomenography in nursing research

AIMS: This paper examines phenomenography, a research approach designed to answer certain questions about how people make sense of their experience. The research approach, developed within educational research, is a content-related approach investigating the different qualitative ways in which people make sense of the world around them. The outcomes of phenomenographic research are different content-related categories describing the differences in other people's ways of experiencing and conceiving their world. METHODS: The research approach is presented by describing the underlying ontological and epistemological assumptions, describing the research method in detail and providing some examples of phenomengraphic studies in health care and nursing research. The possibilities for applying the methodology to nursing research are discussed, illustrated by research examples. Finally, the future role of the approach within nursing research is discussed. CONCLUSION: The emphasis on differences in the phenomenographical research approach makes it distinct from other research approaches, and accordingly, it seems to be reasonable to incorporate knowledge of this kind in the professional education of health care personnel.     

Recombinant factor VIII SQ--stability of VIII: C in homogenates from porcine, monkey and human subcutaneous tissue

The aim of this paper was to investigate whether a formulation-based approach to understanding and addressing stability could generate a subcutaneous factor VIII preparation for patients as an alternative to the existing intravenous products. The low bioavailability of subcutaneously administered factor VIII could have several causes: proteolytic degradation of the protein in the interstitium; adsorption to tissue, in particular to acidic phospholipids such as L-alpha phosphatidyl-L-serine (phosphatidylserine); the absence of free von Willebrand factor in the interstitium; phagocytosis by macrophages in the interstitium or in the lymph nodes; and coagulation could be initiated upon injection. This study was undertaken to investigate the first three factors in-vitro (i.e., proteolytic degradation, adsorption to tissue and the protective effect of von Willebrand factor). The influence of some other macromolecular stabilisers and protease inhibitors was also investigated. The stability of factor VIII activity (VIII: C) was investigated in homogenates from porcine, monkey and human subcutaneous tissue. Possible coagulation was prevented in these studies by the presence of both citrate and antithrombin. An exploratory in-vivo study was performed in the pig; plasma samples were assayed with a factor VIII:Ag (90kDa) ELISA. The decrease in VIII:C appeared to be more pronounced in homogenates from monkey and human tissues than in porcine homogenate. The results from human tissue homogenate resembled the degradation profile seen in monkey homogenate. Both the von Willebrand factor and phosphatidylserine/phosphatidylcholine (PS/PC) liposomes showed a significant stabilising effect on VIII:C in the tissue homogenates. The qualitative pattern was similar in porcine, monkey and human tissue. A combination of several protease inhibitors seemed to have a protective effect on the stability of VIII: C albeit at high concentrations of inhibitors and the effect was less than that of PS/PC. An exploratory in-vivo study was performed in the pig with phosphatidylserine in two formulations; either in the form of PS/PC liposomes or together with Polysorbate 80 in the form of mixed micelles (phosphatidylserine/P80). Including phosphatidylserine in the formulations appeared to increase the availability, of subcutaneously administered r-VIII SQ in the pig. However, further studies are necessary, preferably in the monkey where in-vitro studies indicate a closer resemblance to the human. In conclusion, a proposed inactivation mechanism for r-VIII SQ in subcutaneous tissue could be adsorption to phospholipid surfaces followed by proteolytic degradation. However, additional studies are required due to the multitude of factors influencing the subcutaneous absorption route. A combination of protease inhibitor(s) together with phosphatidylserine-containing liposomes are suggested for further investigation, preferably in a monkey animal model.     

Patients with coeliac disease have a characteristic gliadin antibody pattern

By use of an immunoblotting technique we have investigated the specificity of circulating IgG antibodies with respect to reactions with the alpha-, beta-, gamma- and omega-fractions of gliadin in patients with coeliac disease and in patients with diarrhoea of other causes. Untreated coeliac patients show a characteristic reactivity against polypeptides in the gamma-fraction, with an Mr of 35 and 45 kilodaltons, but only minor reactivity against the other fractions. One coeliac patient exclusively had antibodies to a 80 kilodalton component. Such a reaction pattern was not observed in other groups of patients with diarrhoea, as they had only weak reactions against the gamma-fraction but a stronger reaction against the other fractions. This might indicate that enterocytes of coeliac patients specifically take up distinct polypeptides of gamma-gliadin and by transcellular transport present them to immunocompetent cells. The results also suggest that there are distinct components of gliadin that provoke symptoms in different coeliac patients, indicating a heterogenecity of the disease. The study might lead to new diagnostic methods and to elucidation of the pathogenetic mechanisms behind coeliac disease.     

Peptide quantitative structure-activity relationships, a multivariate approach

The variation in amino acid sequence within sets of peptides is described by three principal properties, z1, z2, and z3, per varied amino acid position. These principal properties are derived from a principal components analysis of a matrix of 29 physicochemical variables for the 20 coded (in mRNA) amino acids. The scales z1, z2, and z3 are used to construct informative sets of analogues for exploring and developing quantitative structure-activity relationships (QSAR) of peptides. For the QSARs, the multivariate partial least squares (PLS) method is used. Multivariate QSARs are developed for four families of peptides, and it is shown how these QSARs can predict the activity of new peptide analogues.     

HIV and AIDS related knowledge,sources of information,and reported need for further education among dental students in Sudan- a cross sectional study

Background  

Information on the HIV and AIDS-related knowledge among dental students provides a crucial foundation for efforts aimed at developing an appropriate dental curriculum on HIV and AIDS, and for attracting the attention of dental school educators towards the subject.     

Flexibility of the use of residual tibial anterior motor units during walking in neuromuscular diseases

The use of tibial anterior (TA) motor units in lower motoneurone disorders was studied during comfortable walking that was the main function of TA. The findings were compared to those in normal subjects. The loss of TA power was compensated either by increases of recruitment and firing rate of residual TA units or by a change from the normal plantigrade gait pattern to the infantile digitigrade pattern putting less strain on TA. Moderately paralysed subjects usually maintained plantigrade gait by excessive use of residual TA units but tended to change to digitigrade gait on fatigue thus economizing with remaining TA power. Severely paralysed subjects used digitigrade gait but plantigrade gait could be restored by application of a toe using string, i.e. the string might increase the strain on TA instead of decreasing it.