Experiences of UK African-Caribbean prostate cancer survivors of discharge to primary care.

Objective: Black men are three times more likely to develop prostate cancer (PCa), to do so at a younger age and to experience a more aggressive form than White men. This study aims to understand the experiences of African-Caribbean men with respect to their discharge to primary care following successful PCa treatment and the challenges associated with survivorship.Design: Eight African-Caribbean men, who had been successfully treated for PCa, were recruited through the charity BME Cancer Communities. They participated in a focus group, which took place on the premises of the charity and was audio-recorded. The recording was transcribed and the data were analysed employing thematic analysis.Results: Three overarching themes were developed: Discharge - misconceptions and uncertainties; Survivorship - challenges and ways of coping; Black men and PCa: real and potential discrimination. Participants expressed concerns regarding the lack of information and clarity about what discharge meant, the quality of follow-up care, especially the levels of specialist knowledge among GPs, and the impact of side-effects, particularly erectile dysfunction (ED). Participants linked ED with stereotypes of Black male sexuality, particularly in relation to difficulties of expressing their emotions and psychological distress. African-Caribbean men face particular challenges in dealing with the side-effects of treatment for PCa, which are linked to socially-constructed ideas of masculinity.Conclusion: There needs to be a greater focus in primary care on understanding these issues and providing individualised culturally-sensitive care. In particular, GPs should be aware of sensitivities concerning help-seeking related to culturally-mediated understandings of masculinity.

Experiences of adolescent lung transplant recipients: A qualitative study.

Many young transplant recipients experience psychological distress and adjustment difficulties, yet there is little research investigating lung transplantation from the recipients' perspective. This qualitative study aimed to explore experiences of young people who underwent lung transplantation. Semi-structured interviews were conducted with six lung transplant recipients (aged 15-18). Interviews were analysed using IPA, a qualitative research approach examining how people make sense of their major life experiences. The analysis revealed three master themes: "Living with Dodgy Lungs" outlined how participants dealt with their experiences, managing through accepting or discussing their feelings with others, although talking was often difficult. "The Big Deal" reflected participants' experiences of the process, their expectations, and the contrast of their lives pre- and post-transplant. Inherent in their accounts was the profound meaning ascribed to transplantation, the emotional turmoil, and impact on their lives. "A Sense of Self" illustrated participants' developing identities within their social contexts and at times isolating experiences. The results highlight key areas where adolescent lung transplant recipients could be supported by clinicians, enabling the promotion of psychological well-being. Examples include supporting identity integration post-transplant, facilitating social inclusion, considering alternative means of support, and involving adolescents in healthcare decisions.

How do nurses experience working with adolescents with a diagnosis of 'personality disorder' or 'emerging personality disorder'?

Nurses experience adults with a diagnosis of 'personality disorder' ('PD') as challenging, but nothing is known of their experiences working with young people with a diagnosis of 'PD' or 'emerging PD'. This study aimed to explore the experiences of nurses with this group. Six nurses were interviewed individually and the transcripts analysed employing interpretative phenomenological analysis. Two themes were identified: emotional impact, and conflict and need for support. Participants described powerful emotional responses and heavy time demands as particular challenges. They also reflected on tensions that arose in the wider team and service context. The importance of reflective space, training and the need for specialist approaches, such as therapeutic input, was emphasized by all participants. The study's findings suggest that while there are some similarities to adult services, there are also issues specific to nursing adolescents with 'PD', which merit further attention, including the implications of the lack of diagnostic clarity for treatment approaches and the difficult interpersonal dynamics of the condition. Recommendations for practice include additional training in relation to the theoretical understanding of diagnosis itself and in working therapeutically with young people with the diagnosis, employing approaches that have been found to be useful in adult services.

Investigation of intrathecal transport of NPT002, a prospective therapeutic based on phage M13, in nonhuman primates.

Presently, there are no effective treatments for conditions characterized by protein misfolding, such as Alzheimer's, Parkinson's, and other diseases involving CNS. Since misfolding occurs at the earliest stage of the disease, it is likely to be involved in subsequent pathological developments. It has been found that NPT002 (bacteriophage M13) directly dissociates aggregates of misfolded proteins that form amyloid, including amyloid-ß, tau and α-synuclein. For CNS applications, NPT002 requires delivery to the brain parenchyma, the target tissue. NPT002 is an elongated ~950 nm particle that cannot penetrate into the brain from the blood. Furthermore, phage particles, due to their size, cannot be effectively transported in vivo by diffusion. Considering the physiology of the leptomeningeal space, intrathecal administration appears to be a promising convection-driven avenue for NPT002 delivery. In this paper, we use positron emission tomography to investigate the transport of NPT002 in Macaca fascicularis. The data suggest that approximately 50 % of the administered dose can reach the cerebral leptomeningeal space after a single lumbar intrathecal injection. A biologically significant fraction of the phage then enters the brain, resulting in potentially therapeutic cortical and subcortical exposure.

Temperature dependent kinetics (195-798 K) and H atom yields (298-498 K) from reactions of (1)CH(2) with acetylene, ethene, and propene.

The rate coefficients for the removal of the excited state of methylene, (1)CH(2) (a(1)A(1)), by acetylene, ethene, and propene have been studied over the temperature range 195-798 K by laser flash photolysis, with (1)CH(2) being monitored by laser-induced fluorescence. The rate coefficients of all three reactions exhibit a negative temperature dependence that can be parametrized as k((1)CH(2)+C(2)H(2)) = (3.06 +/- 0.11) x 10(-10) T ((-0.39+/-0.07)) cm(3) molecule(-1) s(-1), k((1)CH(2)+C(2)H(4)) = (2.10 +/- 0.18) x 10(-10) T ((-0.84+/-0.18)) cm(3) molecule(-1) s(-1), k((1)CH(2)+C(3)H(6)) = (3.21 +/- 0.02) x 10(-10) T ((-0.13+/-0.01)) cm(3) molecule(-1) s(-1), where the errors are statistical at the 2sigma level. Removal of (1)CH(2) occurs by chemical reaction and electronic relaxation to ground state triplet methylene. The H atom yields from the reactions of (1)CH(2) with acetylene, ethene, and propene have been determined by laser-induced fluorescence over the temperature range 298-498 K. For the reaction with propene, H atom yields are close to the detection limit, but for acetylene and ethene, the fraction of H atom production is approximately 0.88 and 0.71, respectively, at 298 K, rising to unity by 398 K, with the balance of the reaction with acetylene presumed to be electronic relaxation. Experimental constraints limit studies to a maximum of 1 Torr of bath gas; master equation calculations using an approach that allows treatment of intermediates with deep energy wells have been carried out to explore the role of collisional stabilization for the reaction of (1)CH(2) with acetylene. Stabilization is calculated to be insignificant under the experimental conditions, but does become significant at higher pressures. Between pressures of 100 and 1000 Torr, propyne and allene are formed in similar amounts with a slight preference for propyne. At higher pressures propyne formation becomes about a factor two greater than that of allene, and above 10(5) Torr (300 < T (K) < 600) cyclopropene formation starts to become significant. The implications of temperature-dependent (1)CH(2) relaxation on the roles of (1)CH(2) in chemical mechanisms for soot formation are discussed.

A basic smell test is as sensitive as a dopamine transporter scan: comparison of olfaction, taste and DaTSCAN in the diagnosis of Parkinson's disease.

AIM: To evaluate relationship between odour identification, taste threshold, dopamine transporter scan (DaTSCAN) and motor function in early Parkinson's disease (PD) and their diagnostic accuracy. METHODS: Seventy-three patients with early parkinsonism were evaluated by the Unified Parkinson's Disease Rating Scale (UPDRS), DaTSCAN, electrogustometry (EGM) threshold and University of Pennsylvania Smell Identification Test (UPSIT). Olfactory Event-Related potentials (OERP) were performed on 49 patients. At follow-up (mean 15.3 months), patients were diagnosed as 'PD' or 'non-PD'. DaTSCAN images were assessed visually and semi-quantitatively by QuantiSPECT. RESULTS: The sensitivity of UPSIT (86%) was not significantly different from that of the DaTSCAN (92%). UPSIT correlated moderately with DaTSCAN uptake (r = 0.44; P < 0.005) and UPDRS score (r = 0.43; P < 0.05) and weakly with symptom duration (r = 0.25; P < 0.05). In the PD group, OERP showed increased latency but no change in amplitude and no correlation with DaTSCAN. EGM thresholds were impaired in 22% of the PD group but they did not correlate with any other test parameters. DaTSCAN-UPSIT discordance was found in nine patients with PD, but neither was diagnostically superior. CONCLUSION: Our patients with early PD have a frequent and severe olfactory deficit that correlates with disease severity, symptom duration and DaTSCAN but not EGM. The sensitivities of UPSIT and DaTSCAN are high at 86% and 92%, respectively. Although DaTSCAN is superior for 'localization', UPSIT is considerably 'cheaper', and neither is disease specific. EGM threshold impairment in PD is independent of the smell deficit, and probably signifies advanced disease.

State resolved measurements of a (1)CH(2) removal confirm predictions of the gateway model for electronic quenching.

Collisional quenching of electronically excited states by inert gases is a fundamental physical process. For reactive excited species such as singlet methylene, (1)CH(2), the competition between relaxation and reaction has important implications in practical systems such as combustion. The gateway model has previously been applied to the relaxation of (1)CH(2) by inert gases [U. Bley and F. Temps, J. Chem. Phys. 98, 1058 (1993)]. In this model, gateway states with mixed singlet and triplet character allow conversion between the two electronic states. The gateway model makes very specific predictions about the relative relaxation rates of ortho and para quantum states of methylene at low temperatures; relaxation from para gateway states leads to faster deactivation independent of the nature of the collision partner. Experimental data are reported here which for the first time confirm these predictions at low temperatures for helium. However, it was found that in contrast with the model predictions, the magnitude of the effect decreases with increasing size of the collision partner. It is proposed that the attractive potential energy surface for larger colliders allows alternative gateway states to contribute to relaxation removing the dominance of the para gateway states.

Kinetics and product branching ratios of the reaction of (1)CH2 with H2 and D2.

The reactions of singlet methylene (a(1)A1 (1)CH2) with hydrogen and deuterium have been studied by experimental and theoretical techniques. The rate coefficients for the removal of singlet methylene with H2 (k1) and D2 (k2) have been measured from 195 to 798 K and are essentially temperature-independent with values of k1 = (10.48 +/- 0.32) x 10(-11) cm(3) molecule(-1) s(-1) and k2 = (5.98 +/- 0.34) x 10(-11) cm(3) molecule(-1) s(-1), where the errors represent 2sigma, giving a ratio of k1/k2 = 1.75 +/- 0.11. In the reaction with H2, singlet methylene can be removed by reaction giving CH3 + H or deactivated to ground-state triplet methylene. Direct measurement of the H atom product showed that the fraction of relaxation decreased from 0.3 at 195 K to essentially zero at 398 K. For the reaction with deuterium, either H or D may be eliminated. Experimentally, the H:D ratio was determined to be 1.8 +/- 0.5 over the range 195-398 K. Theoretically, the reaction kinetics has been predicted with variable reaction coordinate transition state theory and with rigid-body trajectory simulations employing various high-level, ab initio-determined potential energy surfaces. The magnitudes of the calculated rate coefficients are in agreement with experiment, but the calculations show a significant negative temperature dependence that is not observed in the experimental results. The calculated and experimental H to D ratios from the reaction of singlet methylene with D2 are in good agreement, suggesting that the reaction proceeds entirely through the formation of a long-lived methane intermediate with a statistical distribution of energy.

Third-party prospective evaluation of patient outcomes after dynamic graciloplasty.

BACKGROUND: Dynamic graciloplasty (DGP) is a complex procedure designed to improve bowel function in patients with end-stage faecal incontinence. Outcomes of DGP were examined in comparison with stoma formation or continued medical management. METHODS: This third-party evaluation comprised a prospective case-comparison study of patient-based and clinical outcomes at a London hospital. Forty-nine patients who underwent DGP during 5 years from 1997 were compared with 87 patients with similar bowel disorders who did not undergo DGP. Outcome measures were quality of life (QoL), symptoms, anxiety and depression. RESULTS: At 2 years after surgery, bowel-related QoL and continence had improved by more than 20 per cent compared with the preoperative status for two-thirds of patients who had DGP (P < 0.001). Two-thirds were continent all or most of the time, although one-third experienced disordered bowel evacuation. Large deteriorations on the Nottingham Health Profile pain score occurred in 11 of 34 patients who had DGP, compared with seven of 57 patients in comparison groups (P = 0.027). Patients in comparison groups experienced no significant changes in measured outcomes over the 2 years of follow-up. CONCLUSION: Although DGP is associated with a high level of morbidity, it deserves consideration as an alternative to life with severe and refractory faecal incontinence or stoma formation in people in whom conventional treatments have failed.

Holeboard discrimination learning in mice.

We have adapted to mice a holeboard-learning task, which allows simultaneous assessment of spatial working and reference-memory performance. The holeboard apparatus consists of an open-field chamber with a 16-hole floor insert. Across trials, animals have to learn that the same four holes of 16 are always baited. Here, we show that C57BL/6 mice readily acquire this task within 4 days when submitted to six trials per day or within 8 days when submitted to only four trials per day. We also show that C57BL/6, Swiss-Webster, CD-1 and DBA/2 mice acquire this task similarly, despite the fact that some differences could be observed in measures of exploratory activity during habituation and training. Moreover, the muscarinic antagonist scopolamine disrupts learning at doses of 0.1 and 1.0 mg/kg, although the highest dose appeared to have side-effects. Lastly, we found that amyloid precursor protein transgenic mice have a selective disruption in their working-memory performance only during reversal training (i.e. after a change in the configuration of the baited holes). Overall, our data indicate that this spatial learning task is well adapted to mice and will be useful to characterize spatial memory in various genetic or pharmacological mouse models.

Complex behavior in the formaldehyde-sulfite reaction.

The formaldehyde-sulfite reaction is an example of an "acid-to-alkali" clock. It displays an induction period, during which the pH varies only slowly in time, followed by a reaction event, during which the pH increases rapidly by several units. When the reaction is performed in a closed (batch) reactor, the clock time is found to increase with a decrease in initial concentrations of formaldehyde and sulfite and an increase in the total initial concentration of S(IV). At long times, following the clock event, there is a slow decrease in pH. In an open (flow) reactor, bistability between a low-pH steady state (pH approximately 6-8) and a high-pH steady state (pH approximately 11) is observed. Additionally, we report the existence of sustained, small-amplitude oscillations in pH in this system. An extended kinetic mechanism reproduces the batch behavior but fails to account for the complex behavior observed in the flow reactor. Possible additional reaction steps are discussed.

Preschool child care and risk of overweight in 6- to 12-year-old children.

OBJECTIVE: To determine if there is a relationship between center-based child care attendance from ages 3 to 5 y and future overweight at ages 6-12 y. DESIGN/METHODS: Longitudinal, observational study of child experience and future body mass index. SUBJECTS: A total of 1244 US children aged 6-12 y included in the 1997 Panel Study of Income Dynamics Child Development Supplement. MEASUREMENTS: Parent-reported child care attendance from ages 3 to 5 y, trichotomized as 'none', 'limited' (>0 but <15 h/week), and 'extensive' (> or =15 h/week). Overweight defined as a body mass index > or =95th percentile for age and gender. Candidate covariates (selected a priori): gender, race, age, poverty status, birth weight, hours of television per day, Behavior Problems Index score >90th percentile, and Home Observation for Measurement of the Environment-Short Form (HOME-SF) cognitive stimulation score. RESULTS: Of the potential confounding variables, race, HOME-SF cognitive stimulation score, and age significantly altered the relationship between child care attendance and overweight in the multiple logistic regression model. With these covariates in the final model, limited center-based child care attendance from ages 3 to 5 y was independently associated with a decreased risk of overweight at ages 6-12 y (adjusted odds ratio=0.56, 95% confidence interval 0.34, 0.93) relative to no child care attendance. Extensive center-based child care attendance was not associated with future overweight. CONCLUSIONS: Limited center-based child care attendance during the preschool years was independently associated with a decreased risk of future overweight relative to no child care attendance. Additional studies are needed to clarify these findings.

A novel augmentation strategy for treating resistant major depression.

OBJECTIVE: Treatment-resistant depression is a significant public health concern; drug switching or augmentation often produce limited results. The authors hypothesized that fluoxetine could be augmented with olanzapine to successfully treat resistant depression. METHOD: An 8-week double-blind study was conducted with 28 patients who were diagnosed with recurrent, nonbipolar, treatment-resistant depression without psychotic features. Subjects were randomly assigned to one of three groups: olanzapine plus placebo, fluoxetine plus placebo, or olanzapine plus fluoxetine. RESULTS: Fluoxetine monotherapy produced minimal improvement on various scales that rate severity of depression. The benefits of olanzapine monotherapy were modest. Olanzapine plus fluoxetine produced significantly greater improvement than either monotherapy on one measure and significantly greater improvement than olanzapine monotherapy on the other measures after 1 week. There were no significant differences between treatment groups on extrapyramidal measures nor significant adverse drug interactions. CONCLUSIONS: Olanzapine plus fluoxetine demonstrated superior efficacy for treating resistant depression compared to either agent alone.

Phototransduction in transgenic mice after targeted deletion of the rod transducin alpha -subunit.

Retinal photoreceptors use the heterotrimeric G protein transducin to couple rhodopsin to a biochemical cascade that underlies the electrical photoresponse. Several isoforms of each transducin subunit are present in the retina. Although rods and cones seem to contain distinct transducin subunits, it is not known whether phototransduction in a given cell type depends strictly on a single form of each subunit. To approach this question, we have deleted the gene for the rod transducin alpha-subunit in mice. In hemizygous knockout mice, there was a small reduction in retinal transducin alpha-subunit content but retinal morphology and the physiology of single rods were largely normal. In homozygous knockout mice, a mild retinal degeneration occurred with age. Rod-driven components were absent from the electroretinogram, whereas cone-driven components were retained. Every photoreceptor examined by single-cell recording failed to respond to flashes, with one exception. The solitary responsive cell was insensitive, as expected for a cone, but had a rod-like spectral sensitivity and flash response kinetics that were slow, even for rods. These results indicate that most if not all rods use a single transducin type in phototransduction.

Olanzapine treatment of psychotic and behavioral symptoms in patients with Alzheimer disease in nursing care facilities: a double-blind, randomized, placebo-controlled trial. The HGEU Study Group.

BACKGROUND: Patients with Alzheimer disease (AD) commonly exhibit psychosis and behavioral disturbances that impair patient functioning, create caregiver distress, and lead to institutionalization. This study was conducted to assess the efficacy and safety of olanzapine in treating psychosis and/or agitation/aggression in patients with AD. METHODS: A multicenter, double-blind, placebo-controlled, 6-week study was conducted in 206 elderly US nursing home residents with AD who exhibited psychotic and/or behavioral symptoms. Patients were randomly assigned to placebo or a fixed dose of 5, 10, or 15 mg/d of olanzapine. The primary efficacy measure was the sum of the Agitation/Aggression, Hallucinations, and Delusions items (Core Total) of the Neuropsychiatric Inventory-Nursing Home version. RESULTS: Low-dose olanzapine (5 and 10 mg/d) produced significant improvement compared with placebo on the Core Total (-7.6 vs -3.7 [P<.001] and -6.1 vs -3. 7 [P =.006], respectively). Core Total improvement with olanzapine, 15 mg/d, was not significantly greater than placebo. The Occupational Disruptiveness score, reflecting the impact of patients' psychosis and behavioral disturbances on the caregiver, was significantly reduced in the 5-mg/d olanzapine group compared with placebo (-2.7 vs -1.5; P =.008). Somnolence was significantly more common among patients receiving olanzapine (25.0%-35.8%), and gait disturbance occurred in those receiving 5 or 15 mg/d (19.6% and 17.0%, respectively). No significant cognitive impairment, increase in extrapyramidal symptoms, or central anticholinergic effects were found at any olanzapine dose relative to placebo. CONCLUSION: Low-dose olanzapine (5 and 10 mg/d) was significantly superior to placebo and well tolerated in treating agitation/aggression and psychosis in this population of patients with AD.

Differences between doctor and patient estimates of outcome in male sub-fertility clinic attenders.

Treatment for male factor sub-fertility is limited, with low increases in pregnancy rate. Couples attending a male sub-fertility clinic are provided with prognostic information and advised about treatment options. This study aimed to examine the influence of clinic attendance on male sub-fertility patients' expectations of their partners becoming pregnant. Data were collected on 103 male sub-fertility clinic attenders before and after clinic consultation. Patients' mood and expectations of their partners achieving a pregnancy were recorded and compared with the consultant's expectations. Before consultation, patients expected that following the clinic visit their chance of pregnancy would be increased. Post-consultation, their perceptions of their chances of pregnancy were often inaccurate and were more influenced by their own expectations than by the consultant's view. There was no overall correlation between anxiety or depression and estimation of achieving a pregnancy. The clinical implications of these findings are discussed.

SW.B6-Soa(b) nontaster congenic strains completed and a sucrose octaacetate congenic quartet tested with other bitters.

Ten SW.B6 SOA nontaster strains congenic with the SWR/J SOA taster inbred strain were bred via repeated backcross-intercross cycles, with selection for nontasting in each cycle. Preference ratio distributions and phenotypic proportions across cycles at 0.1 mM SOA were consistent with monogenic predictions. The SW.B6 mice completed a congenic quartet with the SWR/J, B6.SW SOA taster and C57BL/6J SOA nontaster strains. The Soa locus controlled avoidance differences within the quartet for SOA, raffinose undecaacetate, glucose pentaacetate and brucine. Background genes not linked to Soa controlled avoidance differences for L-phenylalanine and ethanol. Avoidance of bitter picric acid was influenced by the Soa locus, but avoidance of acetic acid was not. The quartet pattern for quinine HCl was unclear, with indications of both Soa and background effects. Two forms of ribose tetraacetate yielded different patterns. Avoidance differences controlled by the Soa locus were found for the pyranose form; however, all four strains avoided the furanose form. The pleiotropic effects of Soa allele substitution within the quartet were limited to a subset of bitter compounds.

Transduction of bitter and sweet taste by gustducin.

Several lines of evidence suggest that both sweet and bitter tastes are transduced via receptors coupled to heterotrimeric guanine-nucleotide-binding proteins (G proteins). Gustducin is a taste receptor cell (TRC)-specific G protein that is closely related to the transducins. Gustducin and rod transducin, which is also expressed in TRCs, have been proposed to couple bitter-responsive receptors to TRC-specific phosphodiesterases to regulate intracellular cyclic nucleotides. Here we investigate gustducin's role in taste transduction by generating and characterizing mice deficient in the gustducin alpha-subunit (alpha-gustducin). As predicted, the mutant mice showed reduced behavioural and electrophysiological responses to bitter compounds, whereas they were indistinguishable from wild-type controls in their responses to salty and sour stimuli. Unexpectedly, mutant mice also exhibited reduced behavioural and electrophysiological responses to sweet compounds. Our results suggest that gustducin is a principal mediator of both bitter and sweet signal transduction.