Stigma, social appearance anxiety and coping in men and women living with skin conditions: A mixed methods analysis.

Background: The psychological impact of living with a skin condition can have a profound impact on quality of life and could cause appearance-related social anxiety. Existing research suggests ambiguous findings in relation to whether the impact of living with a skin condition differs between males and females. Objectives: The present study aimed to explore the association between stigma, coping styles and social appearance anxiety in men and women living with a skin condition in the United Kingdom. Methods: 231 participants (n = 199 females, n = 30 males, n = 2 non-binary) completed a cross-sectional online questionnaire, capturing quantitative data with the social appearance anxiety scale (SAAS), the shortened version of the coping inventory for stressful situations (CISS-21), and qualitative data from free-text comments and thematic content analysis. Respondents were also asked to provide additional free text comments in relation to the challenges faced and how these were managed. Results: Content analysis revealed that males and females faced daily practical, social and emotional challenges and coped with them in several ways; with higher levels of social appearance anxiety associated with both higher perceived severity of skin condition and younger age. Males and females appeared equally as emotionally affected by living with a skin condition, with the only significant gender difference being females as significantly more likely to engage in avoidant coping behaviours than males. Conclusions: Living with a skin condition presents daily practical, social, and psychological challenges for males and females that have the potential to impact on quality of life. Findings highlight the need for dermatological care to routinely address these issues, and psychosocial interventions must be made available to promote healthy coping with skin conditions.

Updated results from the phase 3 HELIOS study of ibrutinib, bendamustine, and rituximab in relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma.

We report follow-up results from the randomized, placebo-controlled, phase 3 HELIOS trial of ibrutinib+bendamustine and rituximab (BR) for previously treated chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) without deletion 17p. Overall, 578 patients were randomized 1:1 to either ibrutinib (420 mg daily) or placebo, in combination with 6 cycles of BR, followed by ibrutinib or placebo alone. Median follow-up was 34.8 months (range: 0.1-45.8). Investigator-assessed median progression-free survival (PFS) was not reached for ibrutinib+BR, versus 14.3 months for placebo+BR (hazard ratio [HR] [95% CI], 0.206 [0.159-0.265]; P < 0.0001); 36-month PFS rates were 68.0% versus 13.9%, respectively. The results are consistent with the primary analysis findings (HR = 0.203, as assessed by independent review committee, with 17-month median follow-up). Median overall survival was not reached in either arm; HR (95% CI) for ibrutinib+BR versus placebo: 0.652 (0.454-0.935; P = 0.019). Minimal residual disease (MRD)-negative response rates were 26.3% for ibrutinib+BR and 6.2% for placebo+BR (P < 0.0001). Incidence of treatment-emergent adverse events (including grades 3-4) were generally consistent with the initial HELIOS report. These long-term data support improved survival outcomes and deepening responses with ibrutinib+BR compared with BR in relapsed CLL/SLL.

Platelet sequestration and activation during GalTKO.hCD46 pig lung perfusion by human blood is primarily mediated by GPIb, GPIIb/IIIa, and von Willebrand Factor.

BACKGROUND: Here, we ask whether platelet GPIb and GPIIb/IIIa receptors modulate platelet sequestration and activation during GalTKO.hCD46 pig lung xenograft perfusion. METHODS: GalTKO.hCD46 transgenic pig lungs were perfused with heparinized fresh human blood. Results from perfusions in which αGPIb Fab (6B4, 10 mg/l blood, n = 6), αGPIIb/IIIa Fab (ReoPro, 3.5 mg/l blood, n = 6), or both drugs (n = 4) were administered to the perfusate were compared to two additional groups in which the donor pig received 1-desamino-8-d-arginine vasopressin (DDAVP), 3 µg/kg (to pre-deplete von Willebrand Factor (pVWF), the main GPIb ligand), with or without αGPIb (n = 6 each). RESULTS: Platelet sequestration was significantly delayed in αGPIb, αGPIb+DDAVP, and αGPIb+αGPIIb/IIIa groups. Median lung "survival" was significantly longer (>240 vs. 162 min reference, p = 0.016), and platelet activation (as CD62P and ßTG) were significantly inhibited, when pigs were pre-treated with DDAVP, with or without αGPIb Fab treatment. Pulmonary vascular resistance rise was not significantly attenuated in any group, and was associated with residual thromboxane and histamine elaboration. CONCLUSIONS: The GPIb-VWF and GPIIb/IIIa axes play important roles in platelet sequestration and coagulation cascade activation during GalTKO.hCD46 lung xenograft injury. GPIb blockade significantly reduces platelet activation and delays platelet sequestration in this xenolung rejection model, an effect amplified by adding αGPIIb/IIIa blockade or depletion of VWF from pig lung.

Phase II multicentre trial of oral quisinostat, a histone deacetylase inhibitor, in patients with previously treated stage IB-IVA mycosis fungoides/Sézary syndrome.

BACKGROUND: Quisinostat is a hydroxamate, second-generation, orally available pan-histone deacetylase inhibitor. OBJECTIVES: To evaluate the efficacy and safety of oral quisinostat in patients with previously treated cutaneous T-cell lymphoma (CTCL). METHODS: Patients received quisinostat 8 mg or 12 mg on days 1, 3 and 5 of each week in 21-day treatment cycles. Primary efficacy end point was cutaneous response rate (RR) based on the modified Severity Weighted Assessment Tool (mSWAT). Secondary end points included global RR, duration of response (DOR) in skin, progression-free survival (PFS), pruritus relief, safety and pharmacodynamic markers. RESULTS: Eight of 26 (25 evaluable) patients achieved ≥ 50% reduction in mSWAT score at least once, with confirmed cutaneous response in six (RR 24%). There was a low global RR of 8%. DOR in skin ranged from 2·8 to 6·9 months. Median PFS was 5·1 months. Pruritus relief was more frequent in cutaneous responders (67%) than nonresponders (32%). Serial tumour biopsies revealed an increase in acetylated tubulin, indicating a target effect of histone deacetylase 6. Twenty-one of 26 (81%) patients were withdrawn from the study before or at clinical cut-off; five (19%) continued to receive treatment with quisinostat. The most common drug-related adverse events were nausea, diarrhoea, asthenia, hypertension, thrombocytopenia and vomiting. Grade 3 drug-related adverse events included hypertension, lethargy, pruritus, chills, hyperkalaemia and pyrexia. CONCLUSIONS: Quisinostat 12 mg three times weekly is active in the treatment of patients with relapsed or refractory CTCL, with an acceptable safety profile. Combination therapy with other drugs active in CTCL may be appropriate.

Psychopharmacological characterisation of the successive negative contrast effect in rats.

RATIONALE: Successive negative contrast (SNC) describes a change in the behaviour of an animal following a downshift in the quantitative or qualitative value of an expected reward. This behavioural response has been hypothesised to be linked to affective state, with negative states associated with larger and/or prolonged shifts in behaviour. OBJECTIVE: This study has investigated whether different psychopharmacological treatments have dissociable actions on the SNC effect in rats and related these findings to their actions on different neurotransmitter systems and affective state. METHODS: Animals were trained to perform a nose-poke response to obtain a high-value food reward (four pellets). SNC was quantified during devalue sessions in which the reward was reduced to one pellet. Using a within-subject study design, the effects of acute treatment with anxiolytic, anxiogenic, antidepressant and dopaminergic drugs were investigated during both baseline (four pellets) or devalue sessions (one pellet). RESULTS: The indirect dopamine agonist, amphetamine, attenuated the SNC effect whilst the D1/D2 antagonist, alpha-flupenthixol, potentiated it. The antidepressant citalopram, anxiolytic buspirone and anxiogenic FG7142 had no specific effects on SNC, although FG7142 induced general impairments at higher doses. The α2-adrenoceptor antagonist, yohimbine, increased premature responding but had no specific effect on SNC. Results for the anxiolytic diazepam were mixed with one group showing an attenuation of the SNC effect whilst the other showed no effect. CONCLUSIONS: These data suggest that the SNC effect is mediated, at least in part, by dopamine signalling. The SNC effect may also be attenuated by benzodiazepine anxiolytics.

Initial in vivo experience of pig artery patch transplantation in baboons using mutant MHC (CIITA-DN) pigs.

BACKGROUND: In the pig-to-nonimmunosuppressed baboon artery patch model, a graft from an α1,3-galactosyltransferase gene-knockout pig transgenic for human CD46 (GTKO/CD46) induces a significant adaptive immune response (elicited anti-pig antibody response, increase in T cell proliferation on MLR, cellular infiltration of the graft), which is effectively prevented by anti-CD154mAb-based therapy. METHODS: As anti-CD154mAb is currently not clinically applicable, we evaluated whether it could be replaced by CD28/B7 pathway blockade or by blockade of both pathways (using belatacept + anti-CD40mAb [2C10R4]). We further investigated whether a patch from a GTKO/CD46 pig with a mutant human MHC class II transactivator (CIITA-DN) gene would allow reduction in the immunosuppressive therapy administered. RESULTS: When grafts from GTKO/CD46 pigs were transplanted with blockade of both pathways, a minimal or insignificant adaptive response was documented. When a GTKO/CD46/CIITA-DN graft was transplanted, but no immunosuppressive therapy was administered, a marked adaptive response was documented. In the presence of CD28/B7 pathway blockade (abatacept or belatacept), there was a weak adaptive response that was diminished when compared with that to a GTKO/CD46 graft. Blockade of both pathways prevented an adaptive response. CONCLUSION: Although expression of the mutant MHC CIITA-DN gene was associated with a reduced adaptive immune response when immunosuppressive therapy was inadequate, when blockade of both the CD40/CD154 and CD28/B7 pathways was present, the response even to a GTKO/CD46 graft was suppressed. This was confirmed after GTKO/CD46 heart transplantation in baboons.

Pig-to-monkey islet xenotransplantation using multi-transgenic pigs.

The generation of pigs with genetic modifications has significantly advanced the field of xenotransplantation. New genetically engineered pigs were produced on an α1,3-galactosyltransferase gene-knockout background with ubiquitous expression of human CD46, with islet beta cell-specific expression of human tissue factor pathway inhibitor and/or human CD39 and/or porcine CTLA4-lg. Isolated islets from pigs with 3, 4 or 5 genetic modifications were transplanted intraportally into streptozotocin-diabetic, immunosuppressed cynomolgus monkeys (n = 5). Immunosuppression was based on anti-CD154 mAb costimulation blockade. Monitoring included features of early islet destruction, glycemia, exogenous insulin requirement and histopathology of the islets at necropsy. Using these modified pig islets, there was evidence of reduced islet destruction in the first hours after transplantation, compared with two series of historical controls that received identical therapy but were transplanted with islets from pigs with either no or only one genetic modification. Despite encouraging effects on early islet loss, these multi-transgenic islet grafts did not demonstrate consistency in regard to long-term success, with only two of five demonstrating function beyond 5 months.

Expression of human CD46 modulates inflammation associated with GalTKO lung xenograft injury.

Evaluation of lungs from GalTKO.hCD46 pigs, genetically modified to lack the galactose-α(1,3)-galactose epitope (GalTKO) and to express human CD46, a complement regulatory protein, has not previously been described. Physiologic, hematologic and biochemical parameters during perfusion with heparinized fresh human blood were measured for 33 GalTKO.hCD46, GalTKO (n = 16), and WT pig lungs (n = 16), and 12 pig lungs perfused with autologous pig blood. Median GalTKO.hCD46 lung survival was 171 min compared to 120 for GalTKO (p = 0.27) and 10 for WT lungs (p < 0.001). Complement activation, platelet activation and histamine elaboration were significantly reduced during the first 2 h of perfusion in GalTKO.hCD46 lungs compared to GalTKO (ΔC3a at 120' 812 ± 230 vs. 1412 ± 1047, p = 0.02; ΔCD62P at 120' 9.8 ± 7.2 vs. 25.4 ± 18.2, p < 0.01; Δhistamine at 60' 97 ± 62 vs. 189 ± 194, p = 0.03). We conclude that, in addition to significant down-modulation of complement activation, hCD46 expression in GalTKO lungs diminished platelet and coagulation cascade activation, neutrophil sequestration and histamine release. Because GalTKO.hCD46 lung failure kinetics correlated directly with platelet and neutrophil sequestration, coagulation cascade activation and a rise in histamine levels within the first hour of perfusion, further progress will likely depend upon improved control of these pathways, by rationally targeted additional modifications to pigs and pharmacologic interventions.

Concerns and coping during cancer genetic risk assessment.

OBJECTIVE: To gain an 'in-depth' understanding of patients' concerns and their related coping strategies during the genetic risk assessment process. METHODS: Participants were the 'usual care' arm of a trial of a coping intervention targeted at men and women undergoing assessment of genetic risk for familial cancer. Participants completed questionnaires measuring the degree to which they experienced up to 11 concerns and which of 8 coping strategies they used to respond to each of them at entry into the programme and 1 month subsequently (before they received their risk information). FINDINGS: A majority of participants were at least 'quite worried' about all the identified concerns, although the levels of concern fell over the waiting period. Participants used several strategies in response to their varying concerns - although a primary coping strategy for each concern was identifiable. The emotion-focused strategies of acceptance and positive appraisal were generally used in response to concerns they could not change, and seeking social support was used primarily to gain information, but not emotional support from their family. Cluster analysis identified three unique clusters of coping responses. CONCLUSIONS: Genetic risk assessment comprises a number of different stressors each of which is coped with using different strategies.

Illness representations and distress in women undergoing screening for familial ovarian cancer.

Women with a familial or genetic predisposition to ovarian cancer are at significantly increased risk of developing the disease, and this warrants effective risk management strategies. A clinical trial of ovarian cancer screening (OCS) is being conducted to establish the effectiveness of this risk management strategy. This article reports data from its psychological partner study which aims to evaluate the psychological effects of OCS. Leventhal's Self-Regulatory Model provided the theoretical framework for understanding emotional responses to OCS. The revised Illness Perceptions Questionnaire (IPQ-R) is based on this model and the IPQ-R, adapted to the risk of ovarian cancer, was completed by women (N = 1999) prior to screening. The original IPQ-R factor structure was not replicated but IPQ-R variables explained 14.70% of the variance in women's ovarian cancer-specific distress after controlling for age, general anxiety and depression. Negative emotional representations of ovarian cancer risk and general anxiety were moderately associated with greater ovarian cancer-specific distress whereas cognitive illness representations were weakly related to ovarian cancer-specific distress. Further analyses of data from the ongoing psychological evaluation are needed to determine the predictive utility of IPQ-R variables in explaining distress during OCS.

Targeted disruption of the porcine immunoglobulin kappa light chain locus.

Inactivation of the endogenous pig immunoglobulin (Ig) loci, and replacement with their human counterparts, would produce animals that could alleviate both the supply and specificity issues of therapeutic human polyclonal antibodies (PAbs). Platform genetics are being developed in pigs that have all endogenous Ig loci inactivated and replaced by human counterparts, in order to address this unmet clinical need. This report describes the deletion of the porcine kappa (κ) light chain constant (Cκ) region in pig primary fetal fibroblasts (PPFFs) using gene targeting technology, and the generation of live animals from these cells via somatic cell nuclear transfer (SCNT) cloning. There are only two other targeted loci previously published in swine, and this is the first report of a targeted disruption of an Ig light chain locus in a livestock species. Pigs with one targeted Cκ allele (heterozygous knockout or ±) were bred together to generate Cκ homozygous knockout (-/-) animals. Peripheral blood mononuclear cells (PBMCs) and mesenteric lymph nodes (MLNs) from Cκ -/- pigs were devoid of κ-containing Igs. Furthermore, there was an increase in lambda (λ) light chain expression when compared to that of wild-type littermates (Cκ +/+). Targeted inactivation of the Ig heavy chain locus has also been achieved and work is underway to inactivate the pig lambda light chain locus.

Generation of antibody- and B cell-deficient pigs by targeted disruption of the J-region gene segment of the heavy chain locus.

A poly(A)-trap gene targeting strategy was used to disrupt the single functional heavy chain (HC) joining region (J(H)) of swine in primary fibroblasts. Genetically modified piglets were then generated via somatic cell nuclear transfer (SCNT) and bred to yield litters comprising J(H) wild-type littermate (+/+), J(H) heterozygous knockout (±) and J(H) homozygous knockout (-/-) piglets in the expected Mendelian ratio of 1:2:1. There are only two other targeted loci previously published in swine, and this is the first successful poly(A)-trap strategy ever published in a livestock species. In either blood or secondary lymphoid tissues, flow cytometry, RT-PCR and ELISA detected no circulating IgM(+) B cells, and no transcription or secretion of immunoglobulin (Ig) isotypes, respectively in J(H) -/- pigs. Histochemical and immunohistochemical (IHC) studies failed to detect lymph node (LN) follicles or CD79α(+) B cells, respectively in J(H) -/- pigs. T cell receptor (TCR)(ß) transcription and T cells were detected in J(H) -/- pigs. When reared conventionally, J(H) -/- pigs succumbed to bacterial infections after weaning. These antibody (Ab)- and B cell-deficient pigs have significant value as models for both veterinary and human research to discriminate cellular and humoral protective immunity to infectious agents. Thus, these pigs may aid in vaccine development for infectious agents such as the pandemic porcine reproductive and respiratory syndrome virus (PRRSV) and H1N1 swine flu. These pigs are also a first significant step towards generating a pig that expresses fully human, antigen-specific polyclonal Ab to target numerous incurable infectious diseases with high unmet clinical need.

"I have always believed I was at high risk..." The role of expectation in emotional responses to the receipt of an average, moderate or high cancer genetic risk assessment result: a thematic analysis of free-text questionnaire comments.

It is well-recognised that receipt of cancer genetic risk information can evoke a mix of both positive and negative emotional responses. Objective risk itself is not necessarily predictive of emotional response to receipt of risk information and the Cue Adaptive Reasoning Account (CARA; Renner, 2004) suggests that that the degree to which level of risk is consistent with expectations may influence emotional responses. This paper reports a thematic analysis of the free-text data structured around responses to the three risk labels: average, moderate or high. Data is reported from both 123 women and 15 men, including those with a past or current cancer diagnosis. Reactions to risk information appear to be dependent upon participants' pre-conceived expectations about their level of cancer risk. Many average risk respondents questioned the accuracy of their result, whereas high risk information was often expected. Findings are discussed in relation to the CARA model and clinical implications.

The development of a cancer genetic-specific measure of coping: the GRACE.

OBJECTIVE: Generic measures of coping fail to capture the process of undergoing specific health processes such as cancer genetic risk assessment. The Genetic Risk Assessment Coping Evaluation (GRACE) has been developed to provide greater specificity of measurement. METHOD: Based upon previous research findings, the GRACE measures the degree of stress associated with 11 recognised sources of stress for individuals undergoing the early stages of cancer genetic risk assessment, and the use of up to eight coping strategies they may elicit. This paper reports preliminary data from the piloting of the GRACE within a randomised trial of a coping intervention. RESULTS: Of the 265 participants who completed and returned their baseline questionnaire (prior to being informed of their level of genetic risk), 257 completed the GRACE. The most highly endorsed sources of stress involved concerns relating to family members, endorsed by over 60% of respondents, and concerns about how the participants would cope if found to be at increased risk (59%). Participants made use of multiple coping strategies across different sources of stress. The most frequently reported coping strategies were emotion-focused, which may reflect the stage of the assessment process. CONCLUSION: The completion rates for the matrix and specificity of responses provided suggest that the GRACE may be an acceptable measurement tool. Further data collection and validation is ongoing.

Prolactin induces tuberoinfundibular dopaminergic neurone differentiation in Snell dwarf mice if administered beginning at 3 days of age.

The hypothalamic tuberoinfundibular dopaminergic (TIDA) neurones secrete dopamine, which inhibits prolactin secretion. TIDA neurone numbers are deficient in Ames (df/df) and Snell (dw/dw) dwarf mice, which lack prolactin, growth hormone and thyroid-stimulating hormone. Prolactin therapy initiated before 21 days maintains normal-sized TIDA neurone numbers in df/df mice and, when initiated as early as 7 days, maintains the maximum TIDA neurone numbers observed in dw/dw development, which are decreased compared to those in normal mice. The present study investigated the effect of prolactin dose and species on TIDA neurone development. Snell dwarf and normal mice were treated with saline, 5 microg of ovine prolactin (oPRL), 50 microg of oPRL, or 50 microg of recombinant mouse prolactin (rmPRL) beginning at 3 days of age. Brains were analysed at 45 days using catecholamine histofluorescence, and immunohistochemistry for tyrosine hydroxylase or bromodeoxyuridine. Normal mice had greater (P

Identification of critical members in a sulfidogenic benzene-degrading consortium by DNA stable isotope probing.

Stable isotope probing (SIP) was used to identify the active members in a benzene-degrading sulfidogenic consortium. SIP-terminal restriction fragment length polymorphism analysis indicated that a 270-bp peak incorporated the majority of the (13)C label and is a sequence closely related to that of clone SB-21 (GenBank accession no. AF029045). This target may be an important biomarker for anaerobic benzene degradation in the field.

Knowledge and expectations of women undergoing cancer genetic risk assessment: a qualitative analysis of free-text questionnaire comments.

Individuals undergoing cancer genetic risk assessment have been found to have a poor understanding of the process, which may affect how well they cope with learning their risk. This paper reports free-text data from questionnaires completed by women undergoing a randomised controlled trial of a psychological intervention. Of the 268 women undergoing genetic assessment for familial breast/ovarian cancer risk who were invited to take part in the trial, 157 women returned research questionnaires. Of these, 97 women provided free-text comments upon referral to a cancer genetics clinic, 62 provided comments whilst waiting for risk information (average, moderate or high), and 36 women provided comments following notification of risk. This paper reports a thematic analysis of the free-text data. Themes reflected individuals' poor knowledge and uncertainty about genetic risk assessment. How well individuals responded to learning their risk depended upon whether expectations had been met. Regardless of risk, individuals undergoing cancer genetic risk assessment are likely to benefit from increased information about its process and timescales, and access to increased psychological support. Free-text comments can provide valuable data about individuals' expectations and knowledge of genetics services.

13C-carrier DNA shortens the incubation time needed to detect benzoate-utilizing denitrifying bacteria by stable-isotope probing.

The active bacterial community able to utilize benzoate under denitrifying conditions was elucidated in two coastal sediments using stable-isotope probing (SIP) and nosZ gene amplification. The SIP method employed samples from Norfolk Harbor, Virginia, and a Long-Term Ecosystem Observatory (no. 15) off the coast of Tuckerton, New Jersey. The SIP method was modified by use of archaeal carrier DNA in the density gradient separation. The carrier DNA significantly reduced the incubation time necessary to detect the (13)C-labeled bacterial DNA from weeks to hours in the coastal enrichments. No denitrifier DNA was found to contaminate the archaeal (13)C-carrier when [(12)C]benzoate was used as a substrate in the sediment enrichments. Shifts in the activity of the benzoate-utilizing denitrifying population could be detected throughout a 21-day incubation. These results suggest that temporal analysis using SIP can be used to illustrate the initial biodegrader(s) in a bacterial population and to document the cross-feeding microbial community.

Postnatal regression of hypothalamic dopaminergic neurons in prolactin-deficient Snell dwarf mice.

Both Snell (Pit-1(dw) or (dwj), dw/dw) and Ames (Prophet of Pit-1(df), df/df) dwarf mice fail to produce prolactin (PRL) as well as GH due to deficient transcription factor Pit-1 activity and have reduced numbers of hypothalamic PRL-inhibiting area A12 tuberoinfundibular dopaminergic (TIDA) neurons. It has been reported that the TIDA deficit in Ames dwarf mice develops postnatally as a reduction in number after an initial increase that is comparable to that of normal siblings. The present study was designed to characterize A12 TIDA neuronal development in the Snell dwarf (dw/dw) compared with littermate normal mice. Brains of normal (DW/?) and dw(j)/dw(j) mice were examined at 7, 14, 21, 30, and > or = 60 postnatal days (d) by catecholamine fluorescence and quantification of neuron number after tyrosine hydroxylase immunostaining in dopaminergic (DA) areas A12, A13 (medial zona incerta), and A14 (periventricular nucleus). Fluorescence was less in dw/dw than in DW/? A12 perikarya and median eminence but was not reduced in other DA areas, such as substantia nigra, at all ages; A12 fluorescence was virtually absent in Snell dwarf adults. Numbers of TIDA neurons were comparable in normal and Snell dwarf mice at 7 d. In normal (DW/?) mice, A12 neurons increased in number to adult levels at 14 d and were significantly higher than in Snell dwarf (dw/dw) mice at 14 d (P < 0.05) and at subsequent ages (P < 0.01). In Snell dwarf mice, numbers of A12 neurons did not differ at 7, 14, and 21 d, decreased at 30 d (P < 0.05), and reached, at 60 d, 23% of the population in normal sibling mice (P < 0.01 compared with earlier ages). Neuron numbers in nonhypophysiotropic DA area A13 did not vary with age or phenotype. In A14, cell number was higher in both phenotypes at 14 d (P < 0.05 for DW/?; P < 0.01 for dw/dw); neuron number was lower in dw/dw than in DW/? mice at 30 d (P < 0.05) and 60 d (P < 0.01). Thus, compared with normal mice of the same strain, the A12 deficit is more severe in Snell (dw/dw) than in Ames (df/df) dwarf hypothalamus (48% of DF/?), as previously reported, and develops as a decline from the population present at 7 d rather than first increasing. A reduction in A14 neuron number also occurs in the Snell dwarf. Treatment of DW/dw- and dw/dw-containing litters with ovine PRL (50 mug/d, ip), beginning at 12 or 7 d and continuing until 42 d, resulted in TIDA neuron numbers in Snell dwarfs that were lower than those in normal siblings (P < 0.01 for both) but were higher than in untreated adult dwarfs and comparable to the TIDA population size in dwarfs at 7 d, indicating that PRL maintained this maximal number and prevented TIDA neuron dedifferentiation, which occurs in dwarf postnatal development.

Delivering information about cancer genetics via letter to patients at low and moderate risk of familial cancer: a pilot study in Wales.

Increasing demands upon specialist cancer genetics services have resulted in a need to explore alternative means of delivering genetic risk information to individuals at low-risk of familial cancer. This pilot study investigates patient satisfaction with a letter to low and moderate risk individuals notifying them of their risk. Sixty-six people completed a questionnaire designed to measure satisfaction with the way they had been notified of their cancer risk. Two key findings emerge from the data: first of all, whilst many respondents indicated overall satisfaction with the risk letter, a substantial number wanted more information about their risk; and secondly, low-risk individuals in this study are less reassured by and less satisfied with the risk letter than those at moderate risk. The optimal service provision for delivery of genetic risk information is likely to be one which can best respond to individual differences in information-seeking, distress and risk comprehension. There is a need therefore, for a randomised control trial to compare the effectiveness of a risk notification letter with more traditional telephone risk counselling and the implications of each mode of delivery upon the resources of specialist cancer genetics services.