Breast compression techniques in screening mammography - A Maltese evaluation project.

INTRODUCTION: In screening mammography, the radiographer should be responsible for providing mammograms of high diagnostic value, possibly without subjecting clients to a painful experience. This skill is demonstrated via the technique of breast compression and is explored in this study by analysing insights about methods and underlying principles in regards to this procedure. METHODS: One-to-one semi-structured interviews were conducted with radiographers who perform screening mammography in Malta. For data analysis, a descriptive phenomenological approach following a simplified version of Hycner's (1985) method was adopted. RESULTS: Five general themes were extracted from the data; meeting the client, preparing the client, the mammography procedure, pain from compression and client turnout. It was determined that the participants alter their breast compression technique according to the client rather than following a rigid step-by-step process and that explanation and requesting client feedback are essential to obtain cooperation. Additionally, mammography positioning and compression application are tailored in a way that encourage compliance, however not at the expense of degrading image quality. Ultimately, it is also believed that a proper breast compression technique positively influences client turnout. CONCLUSION: The results of this study demonstrate that radiographers should be flexible in their approach in order to carry out a successful breast compression technique. However, it has also been shown that such effectiveness in practice is gained from experience rather than initial training. If exposed to this study's findings, new mammographers would be able to form a robust core of knowledge before embarking on the challenging specialisation of mammography.

Familial factors in diabetic nephropathy: an offspring study.

AIMS: Familial clustering of diabetic nephropathy in patients with Type 2 diabetes suggests that inherited factors predispose to diabetic nephropathy, but the nature of these factors is uncertain. The aim of the study was to compare the prevalence of known risk factors for nephropathy in non-diabetic offspring of Type 2 diabetic patients with and without nephropathy and in control subjects. METHODS: Three groups of patients were recruited with 40 or 41 subjects in each group. These were subjects having one Type 2 diabetic parent with nephropathy (DN); subjects having one parent with Type 2 diabetes without nephropathy (DnoN), and non-diabetic unrelated control subjects with no personal or parental history of diabetes (Control subjects). RESULTS: The median (interquartile range) albumin/creatinine ratio (ACR) was 1.40 (0.96-2.90) mg/mmol in DN; 0.94 (0.50-1.46) mg/mmol in DnoN and 1.22 (0.66-1.83) mg/mmol in Controls (ANOVA: P = 0.03). ACR was higher in group DN than in DnoN (P < 0.006) and in Control subjects (P < 0.03), but there was no difference between DnoN and Control subjects. Twenty-four-hour ambulatory blood pressure monitoring showed mean daytime systolic blood pressure to be significantly higher in group DN than in DnoN (P < 0.02) or Control subjects (P < 0.01) (ANOVA: P = 0.004). Fasting insulin, HOMA-IR, interleukin-6 (IL-6) and C-reactive protein (CRP) were similar in the three groups. CONCLUSION: Our data provide further evidence that genetic factors are important in determining urinary albumin excretion and renal disease associated with Type 2 diabetes and suggest that genes that affect systemic arterial blood pressure but not those relating to insulin resistance or inflammation are likely to be implicated.

Polymerase chain reaction for diagnosis of genital herpes: a missed opportunity?

This study audited the utilization of herpes simplex virus polymerase chain reaction (HSV PCR) in the investigation of recurrent anogenital ulceration at the Mortimer Market Centre. Clinic guidelines for use of HSV PCR were modified in April 2003 to expand PCR use. Ninety-six case-notes belonging to patients presenting with recurrent anogenital ulceration between 1 April and 16 October 2003 were reviewed and 59 were suitable for inclusion. Details of the investigations carried out at each visit were recorded. HSV PCR was used according to guidelines in eight of the 59 cases studied. This audit showed under-utilization of HSV PCR testing with poor adherence to clinic guidelines when cases of suspected recurrent genital herpes were investigated. This led to under-diagnosis and delay in diagnosis. This audit stresses the importance of informing all clinical staff of the improved sensitivity and relative affordability of HSV PCR compared with HSV tissue culture.

Neural induction in the absence of mesoderm: beta-catenin-dependent expression of secreted BMP antagonists at the blastula stage in Xenopus.

A growing body of work indicates that neural induction may be initiated prior to the establishment of the gastrula mesodermal organizer. Here, we examine neural induction in Xenopus embryos in which mesoderm induction has been blocked by Cerberus-short, a reagent that specifically inhibits Nodal-related (Xnr) signals. We find that extensive neural structures with cyclopic eyes and brain tissue are formed despite the absence of mesoderm. This neural induction correlates with the expression of chordin and other BMP inhibitors-such as noggin, follistatin, and Xnr3-at the blastula stage, and requires beta-Catenin signaling. Activation of the beta-Catenin pathway by mRNA microinjections or by treatment with LiCl leads to differentiation of neurons, as well as neural crest, in ectodermal explants. Xnr signals are required for the maintenance, but not for the initiation, of BMP antagonist expression. Recent work has demonstrated a role for beta-Catenin signaling in neural induction mediated by the transcriptional down-regulation of BMP-4 expression. The present results suggest an additional function for beta-Catenin, the early activation of expression of secreted BMP antagonists, such as Chordin, in a preorganizer region in the dorsal side of the Xenopus blastula.

Bone morphogenetic protein-3 is a negative regulator of bone density.

Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-beta (TGF-beta) superfamily. Many BMPs are produced in bone and show osteogenic activity, suggesting that they may be determinants of bone mass. BMP3 was originally purified from bone as osteogenin, which induces osteogenic differentiation. Recombinant BMP3 (rhBMP3) has no biological activity, however, leaving its role in skeletal growth unclear. Here we show that BMP3 is an antagonist of osteogenic BMPs: BMP3 dorsalizes Xenopus laevis embryos, inhibits BMP2-mediated induction of Msx2 and blocks BMP2-mediated differentiation of osteoprogenitor cells into osteoblasts. These effects appear to be mediated through activin receptors. Finally, Bmp3(-/-) mice have twice as much trabecular bone as wild-type littermates, indicating that BMP3, the most abundant BMP in adult bone, is a negative determinant of bone density.

Cerberus-like is a secreted BMP and nodal antagonist not essential for mouse development.

Mouse cerberus-like (cer-l) is a member of the Cerberus/Dan family of secreted factors. As other members of this family of proteins, Cer-l functions in the extracellular space, inhibiting signaling molecules. Here we show that the neural-inducing and mesoderm-inhibiting activities of Cer-l result from specific binding to BMP and Nodal molecules, respectively. These properties resemble the ones from the related factor Xenopus Cerberus. However, Xenopus Cerberus in addition to BMP4 and Nodal also binds to and inhibits Wnt proteins. We show that Cer-l does not directly inhibit Wnt signals. A null allele of the mouse Cer-l gene was generated by targeted inactivation in ES cells. Homozygous embryos show no anterior patterning defects, are born alive, and are fertile. Since mouse Cer-l and Xenopus Cerberus differ in biochemical activities, we propose the existence of additional members of this family of inhibitors, which may compensate for the loss of cer-l.

Predicting early adolescent substance use: do risk factors differ depending on age of onset?

This study was designed to identify different risk models associated with non-use, first use, and prior substance use among a group of early adolescents. A total of 582 students completed a self-report questionnaire at the beginning and end of sixth grade. Nine predictor variables were used in discriminant function analysis to classify adolescents into three groups. Five variables distinguished non-users (never used by the end of sixth grade) and new users (first used during sixth grade) from prior users (first used before sixth grade). Prior users were found to have weaker decision making skills, more susceptibility to peer pressure, more negative perceptions of school, less confidence in their skills, and an increased likelihood of being male. A second function indicated that new users were similar to prior users in that they had less positive peer relations, were more likely to come from single parent families, and had less knowledge about alcohol and drugs than did non-users. The similarities and differences between new and prior users have implications for future research and prevention programming.

Endodermal Nodal-related signals and mesoderm induction in Xenopus.

In Xenopus, mesoderm induction by endoderm at the blastula stage is well documented, but the molecular nature of the endogenous inductive signals remains unknown. The carboxy-terminal fragment of Cerberus, designated Cer-S, provides a specific secreted antagonist of mesoderm-inducing Xenopus Nodal-Related (Xnr) factors. Cer-S does not inhibit signalling by other mesoderm inducers such as Activin, Derrière, Vg1 and BMP4, nor by the neural inducer Xnr3. In the present study we show that Cer-S blocks the induction of both dorsal and ventral mesoderm in animal-vegetal Nieuwkoop-type recombinants. During blastula stages Xnr1, Xnr2 and Xnr4 are expressed in a dorsal to ventral gradient in endodermal cells. Dose-response experiments using cer-S mRNA injections support the existence of an endogenous activity gradient of Xnrs. Xnr expression at blastula can be activated by the vegetal determinants VegT and Vg1 acting in synergy with dorsal (beta)-catenin. The data support a modified model for mesoderm induction in Xenopus, in which mesoderm induction is mediated by a gradient of multiple Nodal-related signals released by endoderm at the blastula stage.

BMP-binding modules in chordin: a model for signalling regulation in the extracellular space.

A number of genetic and molecular studies have implicated Chordin in the regulation of dorsoventral patterning during gastrulation. Chordin, a BMP antagonist of 120 kDa, contains four small (about 70 amino acids each) cysteine-rich domains (CRs) of unknown function. In this study, we show that the Chordin CRs define a novel protein module for the binding and regulation of BMPs. The biological activity of Chordin resides in the CRs, especially in CR1 and CR3, which have dorsalizing activity in Xenopus embryo assays and bind BMP4 with dissociation constants in the nanomolar range. The activity of individual CRs, however, is 5- to 10-fold lower than that of full-length Chordin. These results shed light on the molecular mechanism by which Chordin/BMP complexes are regulated by the metalloprotease Xolloid, which cleaves in the vicinity of CR1 and CR3 and would release CR/BMP complexes with lower anti-BMP activity than intact Chordin. CR domains are found in other extracellular proteins such as procollagens. Full-length Xenopus procollagen IIA mRNA has dorsalizing activity in embryo microinjection assays and the CR domain is required for this activity. Similarly, a C. elegans cDNA containing five CR domains induces secondary axes in injected Xenopus embryos. These results suggest that CR modules may function in a number of extracellular proteins to regulate growth factor signalling.

The head inducer Cerberus is a multifunctional antagonist of Nodal, BMP and Wnt signals.

Embryological and genetic evidence indicates that the vertebrate head is induced by a different set of signals from those that organize trunk-tail development. The gene cerberus encodes a secreted protein that is expressed in anterior endoderm and has the unique property of inducing ectopic heads in the absence of trunk structures. Here we show that the cerberus protein functions as a multivalent growth-factor antagonist in the extracellular space: it binds to Nodal, BMP and Wnt proteins via independent sites. The expression of cerberus during gastrulation is activated by earlier nodal-related signals in endoderm and by Spemann-organizer factors that repress signalling by BMP and Wnt. In order for the head territory to form, we propose that signals involved in trunk development, such as those involving BMP, Wnt and Nodal proteins, must be inhibited in rostral regions.

The role of paraxial protocadherin in selective adhesion and cell movements of the mesoderm during Xenopus gastrulation.

Paraxial Protocadherin (PAPC) encodes a transmembrane protein expressed initially in Spemann's organizer and then in paraxial mesoderm. Together with another member of the protocadherin family, Axial Protocadherin (AXPC), it subdivides gastrulating mesoderm into paraxial and axial domains. PAPC has potent homotypic cell adhesion activity in cell dissociation and reaggregation assays. Gain- and loss-of-function microinjection studies indicate that PAPC plays an important role in the convergence and extension movements that drive Xenopus gastrulation. Thus, PAPC is not only an adhesion molecule but also a component of the machinery that drives gastrulation movements in Xenopus. PAPC may provide a link between regulatory genes in Spemann's organizer and the execution of cell behaviors during morphogenesis.

Comparison of neurite outgrowth induced by intact and injured sciatic nerves: a confocal and functional analysis.

Mechanisms regulating axon growth in the peripheral nervous system have been studied by means of an in vitro bioassay, the tissue section culture, in which regenerating neurons are grown on substrata made up of tissue sections. Sections from intact and degenerated sciatic nerves proved to be different in their ability to support neurite outgrowth of embryonic chick sensory neurons from both qualitative and quantitative points of view. On denervated nerve sections, the total length of neurites elaborated per neuron was almost twice that found on intact nerve sections. In addition, confocal microscopy revealed a striking difference between intact and denervated nerve substrata: on denervated nerve sections, neurites grew inside the internal structures of endoneurial Schwann cell tubes, within the underlying tissue sections, whereas on intact nerve sections neurites extended along endoneurial basal laminae but never entered Schwann cell tubes. Perturbation experiments were used to analyze some of the molecular determinants that control neurite outgrowth in this system. Antibodies directed against the beta1-integrin subunit inhibited neurite extension on both normal and degenerated rat sciatic nerve tissue. Strikingly, however, differential inhibition was observed using antibodies directed against extracellular matrix molecules. Anti-laminin-2 (merosin) antibodies drastically reduced both the percentage of growing neurons and the total length of neurites on denervated nerve sections, but they did not modify these parameters on sections of normal nerve. Taken together, these results suggest that laminin-2/merosin promotes neurite outgrowth in peripheral nerve environments but only after Wallerian degeneration, which is when axons are allowed to extend within endoneurial tubes.

Cleavage of Chordin by Xolloid metalloprotease suggests a role for proteolytic processing in the regulation of Spemann organizer activity.

The Xolloid secreted metalloprotease, a tolloid-related protein, was found to cleave Chordin and Chordin/BMP-4 complexes at two specific sites in biochemical experiments Xolloid mRNA blocks secondary axes caused by chordin, but not by noggin, follistatin, or dominant-negative BMP receptor, mRNA injection. Xolloid-treated Chordin protein was unable to antagonize BMP activity. Furthermore, Xolloid digestion released biologically active BMPs from Chordin/BMP inactive complexes. Injection of dominant-negative Xolloid mRNA indicated that the in vivo function of Xolloid is to limit the extent of Spemann's organizer field. We propose that Xolloid regulates organizer function by a novel proteolytic mechanism involving a double inhibition pathway required to pattern the dorsoventral axis: [formula in text].

Antibodies directed against the beta 1-integrin subunit and peptides containing the IKVAV sequence of laminin perturb neurite outgrowth of peripheral neurons on immature spinal cord substrata.

Neuron-substratum interactions regulating axon growth in the developing central nervous system of the rat have been studied by means of an in vitro bioassay: the tissue section culture. We have previously shown that purified chicken sensory or sympathetic neurons grown on natural substrata consisting of cryostat sections of neonatal rat spinal cord elaborate numerous long neurites [Sagot et al. (1991) Brain Res. 543, 25-35]. Perturbation experiments, in which neuron-substratum interactions are modified by antibodies and peptides, have allowed us to analyse some of the molecular determinants which control neurite outgrowth in this system. Antibodies directed against the beta 1-integrin subunit, one of the neuronal receptors for extracellular matrix molecules, reduced the percentage of growing neurons by about 30% and the length of neurites by about 50%. In contrast, antibodies directed against laminin-1 or fibronectin, two extracellular matrix proteins transiently expressed in various areas of the developing central nervous system, were unable to block neurite outgrowth. Paradoxically, a peptide containing the IKVAV sequence, which mimics an active sequence of the laminin alpha 1 chain responsible for neurite extension, also blocked neurite outgrowth on neonatal spinal cord substrata. These results indicate that integrin receptors containing the beta 1 subunit may play a role in regulating axon growth in the developing nervous system. Among the putative extracellular matrix ligands for these receptors, laminin and fibronectin do not appear as prominent candidates in the neonatal spinal cord. However, our data also suggest that the developing central nervous system may contain neurite outgrowth-promoting proteins carrying the IKVAV sequence, different from laminin-1.