Experiences of and perspectives on genetic testing for breast/ovarian cancer in and outside of the customary clinical setting.

Recently, genetic testing has begun to move from the customary clinical setting (with restrictive entry criteria) into the offices of GPs and the homes of consumers (Williams-Jones, 2003). This research aimed to look at participants' experiences of genetic testing for hereditary breast and ovarian cancer in a clinical environment, and subsequently ascertain potential psychosocial issues associated with genetic testing outside the customary clinical setting. Semi-structured interviews were conducted with eight female participants who had undergone genetic testing within a clinical setting. Transcripts were analysed using Interpretative Phenomenological Analysis. Three super-ordinate themes emerged. Participants' 'battle for control' reflected a perceived loss of control due to their cancer experiences. The 'psychological impact of having experienced/witnessed cancer' highlighted the psychological burden that many participants and their family members lived with. Finally, 'scepticism towards testing outside the clinical setting' was expressed by all participants; they were suspicious of this method of testing. These themes highlighted the potential psychological strain of undergoing genetic testing outside the clinical setting. They also highlighted the wariness with which participants approached the possible introduction of testing outside the customary clinical setting. Psychosocial implications of genetic testing outside the clinical setting were discussed in light of these findings.

External breast prostheses in post-mastectomy care: women's qualitative accounts.

A good-quality external breast prosthesis and prosthesis-fitting service is an integral part of the recovery process post-mastectomy. However, this is an area of care that has minimal information or research available. The aim of this research was to investigate women's experience of the provision, fitting, supply and use of breast prostheses in Ireland. To ascertain women's own personal and subjective experiences, five focus groups with 47 women recruited through national cancer advocacy/support organizations and four Follow-up Breast Clinics throughout Ireland were conducted. As a result, five main themes emerged: (1) The fitting experience--Fitting? (2) Post-mastectomy products--Having? (3) Cost--Affording? (4) Information--Knowing? and (5) Adaptation--Accepting? The emerging themes pinpointed the impact of the fitting experience, fitting environment and the qualities of a prosthesis fitter on a woman's experience in obtaining a first or replacement breast prosthesis; the importance of the physical characteristics of the prosthesis and mastectomy bras; cost, affordability and entitlements; a lack of and perceived difficulty in getting information; and the myriad of personal and social impacts of a breast prosthesis for the woman. These findings are integral for the development of standards of practice in the fitting and supply of external breast prostheses in post-mastectomy care.

Experiences in the provision, fitting and supply of external breast prostheses: findings from a national survey.

A good-quality external breast prosthesis and prosthesis-fitting service is integral to recovery post-mastectomy. However, this area of care has minimal information or research available. The aim of this study was to investigate women's experience of the provision, fitting, supply and use of breast prostheses in Ireland. Three national surveys were undertaken with women (n = 527), breast care nurses (BCNs) (n = 32) and retail prosthesis fitters (n = 12). The findings identified the importance of the prosthesis for shape, appearance to self, appearance to others, sense of well-being, self-confidence and femininity. Dissatisfaction with weight, comfort and movement of the prosthesis was identified. Cost and travel distance were found to influence the replacement of the prosthesis. Dissatisfaction emerged with the display and choice of products, and brochure availability at the prosthesis fitting. Women preferred to be fitted for the first silicone prosthesis by a BCN in a hospital setting whereas for the replacement prosthesis they preferred a trained fitter at a specialized prosthesis supplier. BCNs and retail fitters identified the need for service guidelines and increased availability of professional development opportunities in prosthesis-fitting. These findings contributed to the development of standards of care for breast prosthesis-fitting services to benefit women and to provide guidelines for those providing the service.

Reduce the rads: a quality assurance project on reducing unnecessary chest X-rays in children with asthma.

OBJECTIVES: To quantify and then reduce the number of unnecessary chest X-rays (CXR) being performed on children presenting with asthma. METHODS: A retrospective review of case notes of all children, aged 1-15 years, who presented with asthma and had a CXR performed. The setting was two General Hospitals that see all children presenting to an emergency department in the region. The period of review was before and after the development and implementation of a simple guide for staff, with an education programme, outlining when CXR were deemed unnecessary (known asthmatic, primary diagnosis asthma, improving with treatment, pneumothorax not suspected, and not in Intensive Care Unit). RESULTS: In the 12 months prior to the education programme, 466 children presented with asthma: 260 had a CXR, of which 211 (81.1%) were unnecessary. During the 6 month period following implementation of the programme 197 presented with asthma: 72 had a CXR, of which 56 (78%) were deemed unnecessary. However the percentage of all children presenting with asthma who had an unnecessary CXR fell from 45.3% (211/466) to 28.4% (56/197): P = 0.00005. There was also a decrease in the admission rate from 46% before to 31% after the period of education. CONCLUSION: This study determined that an unacceptably high rate of unnecessary CXR was being ordered in children presenting to hospital with asthma. It also showed how a clinically and statistically significant reduction in the overall number of CXR could be achieved, through a simple and easy to implement educational programme. Further measures are needed in addition to ongoing education in order to improve on this achievement.

Training in general paediatrics: is it time for change?

OBJECTIVE: To determine current Australian general paediatrician's perceptions regarding the adequacy of their training particularly in the new morbidity (NM) area (developmental, behavioural and psychosocial). To ascertain if there is a perceived need to change training in this area, the level of support for change and to canvass opinion on how to achieve change. METHODS: Australian general paediatricians were surveyed by mail in April 2002. The data obtained from those trained before and after the 1992 changes to training were compared by chi(2) analysis. RESULTS: The response rate was 76%. More than one in five new referrals were for NM problems according to 62% of the respondents. The majority (67%) of respondents reported that they were poorly or very poorly trained for NM work in contrast to a majority (82%) who rated that they were well or very well trained for general paediatric work (P < 0.001). Respondents believed that they were poorly or very poorly trained in the use of stimulants (74%), selective serotonin reuptake inhibitors (SSRIs) (93%), tricyclic antidepressants (TCAs) (79%) and clonidine (86%), despite a third of scripts being for one of these medications. The majority of all general paediatricians (90%) want changes to advanced training. Seminars/tutorials, organized visits to general paediatricians' rooms and a mandatory 12 month NM term were the most highly supported options for change. CONCLUSIONS: In view of the prevalence of the NM problems, the perception of inadequate training and the overwhelming support for change it is time for new models of training to be developed and tested.

Abolishing the bag: a quality assurance project on urine collection.

OBJECTIVE: To audit practice in diagnosis of urinary tract infection (UTI) and implement a protocol to reduce the number of falsely diagnosed or misse

The death programme in cultured sympathetic neurones can be suppressed at the posttranslational level by nerve growth factor, cyclic AMP, and depolarization.

We have examined whether sympathetic neurones that have lost the potential to be rescued by protein and RNA synthesis inhibitors after a period of nerve growth factor (NGF) deprivation are irreversibly committed to die. We found that 15 h after withdrawal of NGF from 7-day cultures of neonatal rat superior cervical ganglion neurones, 50% of the neurones lost the potential to be rescued by cycloheximide but that NGF rescued most of the neurones. By 22 h after NGF withdrawal, only 10% of the neurones were rescued by inhibition of macromolecular synthesis with cycloheximide, puromycin, or actinomycin D, but as many as 60-80% of the neurones were rescued by NGF. This is after the time at which a DNA "ladder," consistent with cell death by apoptosis, was first detected (18 h). As long as 27 h of NGF withdrawal was required before 50% of the neurones lost the potential to be rescued by NGF. The survival-promoting agent 8-(4-chlorophenylthio)cyclic AMP (CPTcAMP) or depolarization with 50 mM KCl (HK) rescued neurones with kinetics similar to those of NGF, and rescue by all three agents did not require protein synthesis. Thus, NGF, CPTcAMP, and HK can rescue neurones deprived of NGF at much later times than either protein or RNA synthesis inhibitors by acting at the posttranslational level, a finding suggesting that initiation of the cell death programme in sympathetic neurones is not an irreversible step.

Nerve Growth Factor is Required for Induction of c-Fos Immunoreactivity by Serum, Depolarization, Cyclic AMP or Trauma in Cultured Rat Sympathetic Neurons.

Nerve growth factor (NGF) induces transient Fos-immunoreactivity (Fos-IR) independently of any other factor, both in newly isolated rat sympathetic neurons and in established cultures after NGF deprivation. The same proportion of neurons that express Fos-IR in response to NGF also survive. In addition to direct stimulation of Fos-IR expression, the presence or recent exposure to NGF is required to obtain Fos-IR expression by other stimuli. In newly isolated neurons no Fos-IR is detected in response to stimulation by serum alone and a response to depolarization or cyclic AMP is obtained only if neurons are stimulated within a short period after ganglion excision. In established cultures none of these stimuli, nor the trauma of cutting neurites or spiking cell bodies with a microinjection needle induce Fos-IR unless NGF is present or had been removed for <8 - 16 h. The lack of response is not due to a general decrease in the rate of protein or RNA synthesis. These findings show that in regenerating sympathetic neurons NGF induces c-Fos and suggest that NGF may activate a master trigger that is required for c-Fos expression to be induced by other stimuli.

Partial transcription map of Marek's disease herpesvirus in lytically infected cells and lymphoblastoid cell lines.

Marek's disease herpesvirus (MDV) can cause either a productive-restrictive or lytic infection, a latent infection or can transform thymus-derived lymphocytes. RNA was extracted from infected chicken embryo fibroblasts (CEF) or from lymphoblastoid tumour cell lines. Some of the infected CEF were treated with 200 micrograms/ml cycloheximide to identify immediate early (IE) transcripts, and others with 1 microM 1-(2-fluoro-2-deoxy-B-D-arabinofuranosyl)-5-methyluracil (FMAU), an inhibitor of herpesvirus DNA synthesis to identify early transcripts. An extensive Northern blot analysis was carried out using DNA probes spanning almost the complete MDV genome. In the lytically infected CEF at least 66 discrete transcripts were detected, ranging in size from 9.1 kb to 0.6 kb. Eleven IE transcripts were identified, of which 8 were mapped in the genome segment consisting of the IRL, IRS, US and TRS. Six transcripts were identified as early genes. In the MD lymphoblastoid cell lines MDCC-HPI, a non-producer cell line, and MDCC-CU41, a non-expression cell line, 4 and 7 transcripts were detected, respectively. These RNAs were transcribed from IE genes located mainly in the repeat sequences flanking UL and US and in US. Treatment of the lymphoblastoid cell lines with 20 micrograms/ml 5-iodo-2-deoxyuridine resulted in the additional transcription of 1 RNA species in HPI and 9 in CU41. Most of the transcripts present in lytically infected cells were also detected in MDCC-CU36, a cell line with a high percentage of antigen-positive cells (expression cell line).

Gene sequence and mapping data from Marek's disease virus and herpesvirus of turkeys: implications for herpesvirus classification.

Purified DNAs from Marek's disease virus (MDV) and the herpesvirus of turkeys (HVT) were randomly sheared and cloned into the M13 bacteriophage. Two-hundred and ten MDV and 130 HVT clones were sequenced to give representative samples of the genome sequences. The predicted amino acid sequences from these gammaherpes-viruses were compared to known sequences from other herpesviruses using computer analysis. Thirty-five MDV and 24 HVT genes were identified by comparison with varicella-zoster virus (VZV), an alphaherpesvirus. However, only 14 MDV and seven HVT genes, giving generally lower homology scores, were found by comparison with Epstein-Barr virus (EBV), a gammaherpesvirus, indicating that MDV and HVT sequences bear greater similarity to VZV than to EBV sequences. A number of sequences were mapped by hybridizing labelled M13 clones to Southern blots of restriction fragments of MDV or HVT DNA. The results were consistent with the MDV and HVT genomes being collinear with VZV.

Identification of a new glycoprotein of herpes simplex virus type 1 and genetic mapping of the gene that codes for it.

A type-specific monoclonal antibody, LP10, precipitated a glycoprotein with a molecular weight of approximately 59,000 from purified herpes simplex virus type 1. Although this glycoprotein was similar in size to glycoprotein D (gD), it was shown to be less abundant in both virions and infected cells, to migrate more rapidly in its precursor form, to incorporate glucosamine but not mannose, and to have a more stable precursor in tunicamycin-treated cells than the gD precursor (pgD). Immunoassays of cells infected with insertion recombinants and intertypic recombinants localized the gene coding for the target antigen of LP10 to the unique short (Us) region at map units 0.892 to 0.924 excluding gD. The target antigen of LP10 was then definitively mapped to the Us4 open reading frame by immunoprecipitation of a polypeptide synthesized by in vitro translation of a Us4-specific transcript prepared by using an SP6 cloning This newly identified glycoprotein product of the Us4 gene of herpes simplex virus type 1 is distinct from the previously identified gB1, gC1, gE1, and gH1.

Characterization of the 92,000-dalton glycoprotein induced by herpes simplex virus type 2.

Evidence is presented showing that the 92,000-dalton glycoprotein (g92K) induced by herpes simplex virus (HSV) type 2 has properties distinct from those assigned to any other HSV glycoprotein. First, the carbohydrate composition and extent of sulfation differ from those of glycoproteins D and E. Second, two clonally unrelated monoclonal antibodies, AP1 and LP5, shown in this paper to specifically immunoprecipitate g92K, do not react with any of the known processed forms of glycoproteins B, C, D, and E. Third, by using HSV type 1/HSV type 2 intertypic recombinants and a simple radioimmunoassay, the target antigen of the two monoclonal antibodies was shown to map in the same region as g92K (0.846 to 0.924). Fourth, the intertypic recombinant R12-3 was shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of infected cells to induce the HSV type 2 g92K and HSV type 1 gD and GE, whereas R12-1, which did not induce g92K, induced HSV-2 gE and an altered gD, providing genetic evidence that g92K is encoded, at least in part, by a different region of the genome from that encoding gD and gE.

Role of neutralizing antibodies and T-cells in pathogenesis of herpes simplex virus infection in congenitally athymic mice.

Congenitally athymic nude mice were infected with 10(4) p.f.u. herpes simplex type 1 (strain SC16). Following the passive transfer of neutralizing monoclonal antibodies (AP7, AP8 and AP12) it was observed that AP7 alone reduced the virus infectivity in the nervous system; AP8 and AP12 failed to protect mice probably due to poor in vivo binding to the neutralization site on the virus. Latent ganglionic infection could be established in nude mice following adoptive transfer of optimum number (2 x 10(7) cells/mouse) of immune lymph node cells from day 7 herpes virus-infected hairy immunocompetent donor mice. Moreover, in some of the immune lymph node cell protected nudes, latency could be maintained even in complete absence of neutralizing antibodies. Results of ear-ablation experiments revealed that removal of primary source of infection after day 5 of infection reduced the amount of virus in the ganglia and spinal cord. Acute neurological infection was not detected following transfer of protective anti-gp-D neutralizing antibody (LP2) in combination with removal of infected pinna. These data suggest that continuous seeding of virus occurs in related ganglia via the axonal route from infected ear pinna. It appears that local T-cell-mediated immune mechanisms are involved in maintenance of latency.