Growing older with post-traumatic stress disorder.

WHAT IS KNOWN ON THE SUBJECT?: The needs of older people with long-term mental illness are not very well addressed in policy and research. Older people are not a homogenous group and people ageing with long-term mental illness have potentially unique or specific needs. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: A unique example of the idiosyncratic and contextual nature of individual strengths and the abilities in managing personal recovery when experiencing long-term mental illness. Emotional exhaustion experienced after long-term mental health compromises the ability to manage feelings, potentially a special feature of life time mental ill health. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Recognition that the hard work involved in successfully managing long-term personal recovery may be important in preventing suicide in later life. The need to understand a person's life story to make sense of their experience of mental illness and to recognize long-term mental illness to later life as part of a persons' established identity. The importance of appreciating the place of early memories for understanding older person's mental health in their present. ABSTRACT: Introduction Ageing with mental illness is a neglected area of research and policy. People who grow older to later life with ongoing mental health problems may not have their needs well understood. This understanding is important if mental health services are to ensure direct or indirect age discrimination is avoided. Aim This paper aims to explore issues relating to later life and ageing with mental illness focused on the story of Bernard (who was 84 years of age at the time of writing) who lived with a diagnosis of post-traumatic stress disorder (PTSD). Method The paper is co-authored by Bernard and the researcher he originally told his story to as a participant in a biographical research study exploring mental ill health through the life course. In the original research study, Bernard completed a curriculum vitae (CV) of his life which informed two personalised interviews. An edited version of this is presented in this paper. Implications for practice are discussed in the context of life course, recovery, self-help and preventing suicide. The narrative illustrates how time, memory and meaning interweave and how ageing with mental illness become part of a person's ongoing identity.

SU-E-T-312: Optically Stimulated Luminescent Dosimeter Performance in High Dose Rate Brachytherapy.

PURPOSE: To investigate the use of optically stimulated luminescent dosimeters (OSLDs) for high dose rate (HDR) Ir-192 brachytherapy. While common in megavoltage radiotherapy applications, the performance of OSLDs using kilovoltage energies, high dose gradient and high dose rate regions ubiquitous to HDR has not been demonstrated. METHODS: Commercially available nanoDotTM (Landauer, Glenwood, IL) OSLDs - 5mm diameter and 0.2mm thickness - were irradiated using an Ir-192 source in various geometries to determine dose rate dependence. Angular geometries were created using a circular applicator designed for accelerated partial breast irradiation by Accuboost®. RESULTS: Response remained linear for high doses and was independent of dose rate. Specifically, the OSLDs were shown to be linear with dose up to 200 cGy then became slightly supra-linear up to 600 cGy. There was a slight angular dependence for OSLDs which becomes significant in 'edge-on' scenarios. An asymmetry in this angular dependence was discovered, but was attributed to cable curvature, point source approximation, and positioning within its plastic casing. CONCLUSIONS: Clinical HDR doses of 300 cGy fall within the linear, dose-rate-independent region. Angular independence can be maintained by avoiding extreme 'edge-on' measurement geometries. Because of re- readability, OSLDs can serve as a permanent record or alternatively be annealed within a few hours using conventional fluorescent light. Lastly, OSLDs are produced for only $5 each. Due to these features, in conjunction with the dosimetric performance, OSLDs should be considered a reliable tool for in vivo HDR brachytherapy measurements.

SU-E-T-176: Improved Collimator Scattering Factor (Sc) Measurements for Small Fields Using Build-Up Caps in Robotic Radiosurgery.

PURPOSE: The Monte Carlo calculation algorithm in the MultiPlan (Accuray, Palo Alto, CA) treatment planning system used for CyberKnife (Accuray) robotic radiosurgery requires in-air measurements. In this study, results were compared for the impact of build-up caps using a diode detector for small field in-air measurements. METHODS: Two acrylic caps custom-made for the SFD diode detector (IBA, Germany) of two thicknesses were compared against free-in-air measurements. The 1.5 and 5 cm thicknesses correspond to Dmax and a depth beyond the range of electron contamination, respectively. A Blue Phantom (IBA) was used to position the diode 80 cm SAD. Measurements were made for all 12 fixed cones ranging from 5 to 60 mm. RESULTS: For the 5 mm cone, there is a 15.6% and 20.0% difference in the Sc factor between the 1.5 cm and 5 cm buildup caps, respectively, versus the free-in-air measurement. For the 7.5 mm cone, the difference is 6.3% and 10.4% for the 1.5 cm and 5 cm buildup caps, respectively, versus the free-in-air measurement. While generally decreasing, the Sc factor for either buildup cap does not agree within 2% to free-in-air measurements until the cone used is larger than 40 mm. Overall, the two buildup caps yield similar Sc factors and the differences observed are attributed to electron contamination. CONCLUSIONS: The Monte Carlo calculation algorithm used by the CyberKnife planning manual does not refer to any build-up caps. This study has shown that, particularly for small fields, there are large differences in Sc factors measured with and without buildup caps. In general, for fields smaller than 10 mm, build-up caps should be carefully chosen, especially in commissioning data.

WE-F-211-01: The Evolving Landscape of Scientific Publishing.

The dissemination of scientific advances has changed little since the first peer-reviewed journal was published in 1665 - that is, until this past decade. The print journal, delivered by mail and stored on office shelves and in library reading rooms around the world, has been transformed by immediate, on-demand access to scientific discovery in electronic form. At the same time, the producers and consumers of that scientific content have greatly increased in number, and the balance between supply and demand has required innovations in the world of scientific publishing. In light of technological advances and societal expectations, the dissemination of scientific knowledge has assumed a new form, one that is dynamic and rapidly changing. The academic medical physicist must understand this evolution to ensure that appropriate decisions are made with regard to journal submission strategies and that relevant information on new findings is obtained in a timely manner. Medical Physics is adapting to these changes in substantive ways. This new scientific publishing landscape has implications for subscription models, targeted access through semantic enrichment, user interactivity with content, customized content delivery, and advertising opportunities. Many organizations, including the AAPM, depend on scientific publishing as a significant source of revenue, but web-based delivery raises the expectation that access should be free and threatens this model. The purpose of this symposium is to explore the factors that have contributed to the current state of scientific publishing, to anticipate future directions in this arena, and to convey how medical physicists may benefit from the expanded opportunities, both as authors and as readers. LEARNING OBJECTIVES: 1. To appreciate the importance of scientific and clinical practice communication for the advancement of the medical physics field 2. To understand the roles of the Editorial Board and the Journal Business Management Committee in the promotion and advancement of Medical Physics 3. To explore technology-driven content delivery mechanisms and their role in facilitating content access and driving content usage 4. To understand the potential benefits and pitfalls of various economic and editorial models of scientific publications and the recent shifts away from the traditional role of libraries.

A role for inflammatory mediators in the IL-18 mediated attenuation of LTP in the rat dentate gyrus.

Pro-inflammatory cytokines are known to be elevated in several pathological conditions that are associated with deficits in cognition. We have previously demonstrated that interleukin-18 (IL-18) inhibits long-term potentiation (LTP) in the dentate gyrus in vitro. In this study we have examined the involvement of the inflammatory mediators COX-2 and iNOS in IL-18-mediated inhibition of LTP. The effect of an anti-inflammatory PPARgamma agonist was also investigated. We report that the impairment of LTP by IL-18 is significantly attenuated by prior application of the COX-2 inhibitor, SC-236 and the iNOS inhibitor 1400W. These agents had no effect on paired pulse depression in the dentate gyrus. Furthermore, application of the PPARgamma agonist ciglitazone also attenuated IL-18-mediated inhibition of LTP. We discuss a role for p38 MAP kinase in these effects. This study provides novel evidence for the involvement of inflammatory mediators in IL-18-mediated inhibition of LTP in the rat dentate gyrus in vitro.

Prevalence of Chlamydia trachomatis in sexual contacts of gonorrhoea.

The British national and local clinic guidelines recommend epidemiological treatment for Chlamydia trachomatis (CT) in patients with gonococcal infection but not their contacts. We aimed to determine the prevalence of CT amongst all gonorrhoea contacts attending over a 30 months period through a retrospective notes review. Of 223 contacts, gonorrhoea was diagnosed in 110 (49.3%) while CT was diagnosed in 54 (24.2%). CT was significantly more prevalent in younger people [(37.8% of contacts <25 years versus 9.6% of contacts >/=25 years (P = 0.000)]. All patients with CT identified as heterosexual except one. Amongst heterosexuals, there was no significant difference in the prevalence between males and females, being 31.6% and 27.8% respectively (P = 0.5995). CT was prevalent in 29.1% of N. gonorrhoeae positive contacts and 19.5% of N. gonorrhoeae negative contacts (p = 0.0935). The high prevalence suggests that epidemiological treatment for CT in gonorrhoea contacts is indicated.

Are we getting the message across? Trends among young men attending an inner city young people's clinic.

BACKGROUND: A young people's clinic has been running at the Archway Sexual Health Clinic since 1997. This offers a weekly walk-in service to both young men and women under 20 years old. OBJECTIVES: To review the audit data of over 7 years' experience from the dedicated young people's clinic at the Archway Sexual Health Clinic, the "Arch." METHODS: These data were collected by retrospective notes review of a consecutive series of all male attendees over a 7 year period from 1997 to the end of 2003 with collection of data in Microsoft Excel database. RESULTS: These figures show an overall increase in attendee numbers, but also a relative rise in the numbers of young men using the service. A high number of bacterial sexually transmitted infections were detected. In 2001 and 2003 respectively, 14.5% and 17.8% of the young men using the service were diagnosed with Chlamydia trachomatis. A user survey aimed to identify factors that may be encouraging the young men to access the service. CONCLUSIONS: Responding to the views of young men using the service has played a part in service development. Initiatives at the "Arch" such as the condom policy and choice of gender of staff may be factors encouraging increasing attendances. Continuing to work with other agencies to develop ways to engage young men are recommended. Word of mouth recommendation cannot be underestimated in publicising the service.

A role for c-Jun N-terminal kinase in the inhibition of long-term potentiation by interleukin-1beta and long-term depression in the rat dentate gyrus in vitro.

Recent evidence has emphasised the importance of mitogen-activated protein kinase activation in the modulation of hippocampal synaptic plasticity. Whilst extracellular-regulated kinase activation is now regarded as a critical step in the induction of long-term potentiation (LTP), activation of p38 and c-Jun N-terminal kinase (JNK) is associated with its inhibition. Here, the effects of the novel JNK inhibitor anthra[1,9-cd]pyrazol-6(2H)-1 (SP600125) were investigated on the inhibition of LTP by cytokines interleukin-1beta, interleukin-18 and tumour necrosis factor-alpha in the dentate gyrus. Perfusion of SP600125 alone prior to tetanic stimulation of the medial perforant path did not significantly affect baseline synaptic transmission, post-tetanic potentiation or the magnitude of induced LTP. When SP600125 was perfused onto slices prior to application of cytokines, this resulted in a complete reversal of the cytokine-mediated inhibition of LTP. Moreover, the magnitude of LTP attained in these slices was significantly greater than that obtained in vehicle control slices. Next, we investigated the effects of the JNK inhibitor on the impairment of pharmacologically isolated N-methyl-D-aspartate receptor-mediated potentials (NMDA-EPSPs) by interleukin-18. Whilst not affecting baseline amplitude when perfused alone, prior perfusion of SP600125 alleviated the depressive effect of interleukin-18 on NMDA-EPSPs. Finally, we examined the possibility of JNK involvement in the induction of long-term depression (LTD) in the dentate gyrus. Perfusion of SP600125 prior to low-frequency stimulation of the perforant path resulted in a significant attenuation of induced LTD, which suggests that JNK activation is a critical mediator of LTD in the dentate gyrus. These results directly implicate, for the first time, differential activation of JNK in the modulation of distinct forms of hippocampal synaptic plasticity. Whereas acute over-activation of JNK by pathophysiological concentrations of cytokines is detrimental to LTP, physiologic activation of JNK appears necessary for the induction of LTD.

An urban epidemic--an audit of an inner city young persons' clinic.

In 1996 a young persons' clinic was set up at the Archway Sexual Health Clinic. A retrospective case note review of all attendees for 7 months in 1999 was performed to assess the demography and incidence of sexually transmitted infections (STIs) amongst attenders of the clinic. There were 567 attendances, comprising 364 individuals (331 women and 33 men). Ten per cent of attendees were less than 16 years of age, and 48% were 16-18 years. Fifty-eight per cent were from ethnic minorities. Chlamydial and gonococcal infection was identified in 21.3% and 8.4%, respectively. Thirty-five per cent of new presentations by women involved pregnancy testing, 28.6% were positive. The introduction of the clinic has been successful judged both by the amount of attendances and diseases diagnosed. Specific provision of services for this group needs to be addressed by all sexual health providers.

Hepatic and renal failure associated with amiodarone infusion in a patient with hereditary fructose intolerance.

Hereditary fructose intolerance is a rare inherited metabolic disorder. Although fructose intolerance usually presents in the paediatric age group, individuals can survive into adulthood by self.manipulation of diet. Hospitalisation can become a high.risk environment for these individuals because of loss of control of their strict dietary constraints and the added danger of administration of medications containing fructose, sucrose and sorbitol. We report a case of hereditary fructose intolerance in an adult presenting with hepatic and renal failure associated with an amiodarone infusion and explore the possibility of polysorbate 80 as a cause of this patient's hepatic and renal failure.

The pro-inflammatory cytokine interleukin-18 impairs long-term potentiation and NMDA receptor-mediated transmission in the rat hippocampus in vitro.

The effects of the pro-inflammatory cytokine interleukin-18 (IL-18) were investigated on both normal and isolated N-methyl-D-aspartate (NMDA) receptor-mediated field excitatory post synaptic potentials (fEPSP) and on the induction of long-term potentiation (LTP) in the rat dentate gyrus in vitro. Bath perfusion with IL-18 (100 ng/ml) for 20 min prior to high-frequency stimulation had no significant effect on baseline synaptic transmission or paired pulse depression, but did impair the induction of LTP (115.7+/-8.8% versus 150.8+/-8.1% in vehicle control slices, n=6, P<0.05 at 60 min). Further analysis demonstrated that IL-18 significantly depressed the amplitude of pharmacologically isolated NMDA receptor-mediated fEPSP (NMDA-fEPSP; 77.4+/-4.3% of baseline compared to controls at 1 h; P<0.05, n=7), an effect that may underlie the impairment of LTP by IL-18. This action of IL-18 on LTP and NMDA-fEPSPs was attenuated in full by pretreatment of slices with exogenously applied IL-1 receptor antagonist (IL-1ra, 100 ng/ml), the naturally occurring antagonist of IL-1 type 1 receptors. This ability of IL-1ra to block the inhibitory effects of IL-18 is likely to be receptor-specific as no reversal of the tumour necrosis factor-alpha-induced inhibition of LTP was seen with IL-1ra administration (110.7+/-5.4% versus tumour necrosis factor-alpha-treated slices; 107.4+/-8.7%, P=0.6, n=6). These are the first experiments providing evidence of a direct neuromodulatory role for IL-18 in synaptic plasticity.

Uptake of porcine rubulavirus (LPMV) by PK-15 cells.

BACKGROUND: The porcine virus denominated La Piedad Michoacan Virus (LPMV) is a member of the family Paramyxoviridae and is the cause of a disease in pigs present only in Mexico. The disease is characterized by meningoencephalitis and respiratory distress in young pigs, epididymitis and orchitis in boars, and reproductive failure and abortion in sows. METHODS: The cytopathology, morphology, and distribution of the hemagglutination neuraminidase (HN) and nucleoprotein (NP) proteins of LPMV were investigated following inoculation into PK-15 cells. The cytopathic effect was characterized by cytoplasmic vacuolation and the formation of syncytia and cytoplasmic inclusion bodies. RESULTS: In immunofluorescence assays using a monoclonal antibody (MAb) against the HN protein at 5-60 min post-infection (early infection), a diffuse immunofluorescence was observed near the cell membrane and adjacent to the nuclear membrane. At 24 h post-infection (late infection), a dust-like immunofluorescence was observed throughout the cytoplasm. LPMV-infected cells incubated with the MAb against the NP protein showed punctate cytoplasmic fluorescence during the early stages of infection. At the late infection stage, these fluorescent particles became larger and were seen predominantly in the cytoplasm of syncytia. This pattern was also apparent by immunohistochemical labeling and immunogold electron microscopy. The latter technique revealed that HN protein was diffusely distributed throughout the cytoplasm. When using the MAb against the NP protein, nucleocapsid organization was the most prominent feature and resulted in the formation of cytoplasmic inclusion bodies visible by light and electron microscopy. Immunogold labeling of purified nucleocapsids was shown by electron microscopy. Virus particles and nucleocapsids were morphologically similar to members of the Paramyxoviridae family. CONCLUSIONS: The morphologic characteristics of the virions and the distribution patterns of the HN and NP proteins in PK-15 infected cells indicate that the mechanisms of LPMV replication are generally similar to those of the members of the Paramyxoviridae family.

CD44V6 in gastric carcinoma: a marker of tumor progression.

CD44 is a group of cell surface molecules involved in cell-cell and cell-matrix interactions. CD44 spliced variants (CD44V) have been found to enhance the metastatic potential of rat tumors. Tumors from the breast, colon, and thyroid express many alternatively spliced products; nonneoplastic tissues do not. Some authors suggest that CD44V5 and V6 may play a role in gastric carcinoma. The aim of the current study was to investigate the role of CD44V6 as a prognostic marker and predictor of metastatic potential in gastric carcinomas. One hundred fifty-five cases of gastric adenocarcinomas were studied: 36 cases of early (EGC), 19 cases of intermediate (MGC), and 100 cases of advanced gastric adenocarcinomas (AGC). A monoclonal antibody against CD44V6 (R&D) was used. CD44V6 expression was positively correlated with advanced stage (P = 0.05). Strong positivity was only detected in those cases of AGC with metastases. Patients with CD44V6 positive tumors revealed a lower 3- and 5-year survival rate (P = 0.0002). Immunohistochemical detection of CD44V6 could now be used as an indicator of tumor progression in biopsies of patients with gastric carcinoma.

Where goest the Peacock?

Since the treatment of the first patient in 1994, the Peacock system has maintained its presence as the dominant method of intensity-modulated radiation therapy (IMRT) delivery. Currently in use at nearly 80 institutions, over 8000 patients have been treated using the system. Peacock treatments have been delivered to sites throughout the body, including CNS, head & neck, prostate, liver, kidney, lung, mediastinum, and extremities. IMRT, however, is a young and rapidly evolving treatment methodology. As institutions have explored new ways of improving radiation therapy with intensity-modulated techniques, the requirements for the Peacock system have also expanded. More sophisticated planning algorithms have been implemented to satisfy these new requirements, as well as better tools for treatment verification and quality assurance. In addition, new delivery techniques are being examined to improve the ability of IMRT to increase target volume doses while limiting organ-at-risk doses. One such technique, using helical tomotherapy (Peacock is an example of sequential tomotherapy), is currently being evaluated at one institution. Both techniques use narrow, modulated delivery beams. However, helical tomotherapy requires continuous movement of the couch during radiation, similar to helical CT. This work reviews the development of tomotherapy with the Peacock system. It then looks at current IMRT treatment techniques using tomotherapy, and how the field has broadened since the first treatments were delivered. Finally, it looks at the future of tomotherapy techniques, and how these techniques will adapt to the changing requirements for radiation therapy.

Subtle alterations in growth medium composition can dramatically alter the percentage of unsaturated fatty acids in the yeast Saccharomyces cerevisiae.

The essence of the scientific method is the production of reproducible results in repeated experiments. Cells of the yeast strain DBY747 normally contain 36% unsaturated fatty acids but suddenly, and initially inexplicably, lipid analysis revealed 72% unsaturated fatty acids in the same strain at the same growth temperature. A comparative lipid analysis of DBY747 grown in YEPD and in a number of different types and batches of Yeast Nitrogen Base media revealed two heretofore unreported phenomena. We provide mass spectroscopy and yeast bioassay evidence suggesting that the increase in lipid unsaturation can be attributed to the presence of the plasticizing agent dioctylphthalate in YNB and bactopeptone packaged in 'new' plastic containers first introduced by Difco some 3-4 years ago. We also demonstrate that L-methionine plays an important role in determining the percentage of unsaturated fatty acids in cells grown in laboratory-produced YNB. The results illustrate a novel aspect of methionine metabolism while at the same time highlighting the need for more stringent control to be exercised by the companies that formulate and package defined media.