Characteristics of prisoners with intellectual disabilities.

BACKGROUND: Previous studies have found high rates of intellectual disabilities (ID) in prison. However, little is understood about prisoners with ID. This study aimed to identify prisoners with ID and compare their characteristics with prisoners without neurodevelopmental disorders with regard to demographic profile, mental health, suicide risk and offences. METHOD: This was a descriptive, cross-sectional study carried out using face-to-face interviews with 240 participants in a London Category C prison. Standardised tools were used to assess prisoners for ID and mental disorder. RESULTS: The study identified 18 prisoners as having ID. Participants with ID were less likely to be from a black or minority ethnic background, be over 35 years of age or have any qualifications. They were more likely to have been single, homeless or unemployed before coming into prison. Prisoners with ID were significantly more likely to have mental health problems and 25% had thought about suicide in the last month and 63% had attempted suicide in the past. Prisoners with ID were also more likely to be housed in the vulnerable prisoners' wing and significantly more likely to have committed robbery than other prisoners. CONCLUSIONS: The findings confirm the presence of significant numbers of people with ID with high levels of mental illness in a male prison. Services across the CJS are required for this group, specifically, there is a need for raised awareness among those working in prison about ID and improved skills to recognise offenders with ID and address major gaps in current healthcare provision in prison.

Characteristics of prisoners with neurodevelopmental disorders and difficulties.

BACKGROUND: Previous studies have found high rates of attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and intellectual disability (ID) within the criminal justice system (CJS). However, little is understood about prisoners with neurodevelopmental disorders and difficulties (NDD) or their needs. This study aimed to identify prisoners with NDD and compare their characteristics with prisoners without NDD on a range of socio-demographic and social functioning measures. METHOD: This was a descriptive, cross-sectional study carried out using face-to-face interviews with 240 participants in a London Category C prison. Standardised tools were used to assess prisoners for ADHD, ASD and ID. RESULTS: The study identified 87 prisoners who screened positive for one or more type of NDD. Participants with NDD were significantly younger and more likely to be single [(odds ratio) OR = 2.1], homeless (OR = 3.4) or unemployed (OR = 2.6) before they came into prison. They also had poorer educational achievements that those without NDD. Over 80% of those with NDD had a previous conviction or imprisonment. CONCLUSIONS: The findings confirm the presence of significant numbers of people with NDD in a male prison. Services across the CJS are required for this group; specifically, there is a need for raised awareness among those working in the CJS to improve the recognition of offenders with NDD. Services in the community need to work with individuals with NDD who are at risk of offending, targeting those who are homeless, unemployed and have poor employment opportunities.

Experiences of mental health services by people with intellectual disabilities from different ethnic groups: a Delphi consultation.

BACKGROUND: Patient experience of those accessing mental health services has been found to be different between ethnic groups. Although the needs of people with intellectual disabilities (ID) from different ethnic communities are being increasingly recognised, little has been published about their experiences of mental health services. The aim of this study was to establish whether there are any differences in the experiences of people with ID and mental health problems from two ethnic communities in South London. METHOD: A two-round Delphi process was utilised. White British and Black or Black British service users from a specialist community-based mental health service for adults with ID completed a specially compiled questionnaire. Statements on participants' experiences, including satisfaction with care, staff members' attitudes, cultural awareness and level of support, were rated using a Likert scale. RESULTS: Twenty-four out of 32 participants (75%) completed both rounds of the Delphi consultation. Consensus (≥80% agreement with the group median) was reached for 20 items in the White group and five items in the Black group. All responses that reached consensus were positive about the services that were being received. The Black group were less positive about a range of their experiences, including the use of medication. CONCLUSIONS: People with ID from two ethnic groups were able to successfully complete a Delphi consultation regarding their experiences of mental health services. Broad consensus on positive experiences of services was reached in the White group but not for the Black participants.

Services in the community for adults with psychosis and intellectual disabilities: a Delphi consultation of professionals' views.

BACKGROUND: There remains a severe lack of evidence on the effectiveness of community services for adults with psychosis and intellectual disabilities (ID). There has been little consensus even of what services should provide for this service user group. METHOD: A consultation of multidisciplinary professionals was carried out by using a three-round Delphi exercise. Participants were recruited nationally. They rated their views on the importance of 139 items for the care of adults with psychosis and ID. These included 85 routine service components, 23 service user characteristics for those needing a more intensive service and 31 more intensive service components. RESULTS: Forty-nine out of 52 participants completed all three rounds of the Delphi consultation. Consensus of opinion (> or = 80% agreement as essential) was obtained on 18 of the routine service components, nine of the service user characteristics and five of the more intensive service components. The routine service components considered essential can be broadly considered under a need for a focused approach on the service user and their illness (e.g. monitoring of mental state) and the added need to work within the wider context of the service user with psychosis and ID (e.g. access to social, leisure or occupational activities). Five of the more intensive service components were considered to be essential (e.g. can react to a crisis that day). However, the routine service components considered essential already contained many components such as out-of-hours support and crisis plans also relevant to more intensive services. CONCLUSION: These findings can be used to develop further the evidence base for services in the community for this user group and to assist in the preparation of much needed service evaluation studies.

Escalated median dose for pituitary macroadenomas using intensity-modulated radiation therapy.

Three-dimensional conformal radiotherapy (3D CRT) has become an established treatment for pituitary macroadenomas. This study is an investigation into the possible dosimetric advantages of intensity-modulated radiotherapy for such critically located tumors. Three consecutive patients with pituitary macroadenoma previously treated with 3D CRT were replanned with inverse-planned IMRT using Helax-TMS (V.6.0, Helax AB, Uppsala, Sweden. Fusion of computed tomography (CT) with postoperative magnetic resonance imaging (MRI) was performed within the planning system to define the gross tumor volume (GTV), planning target volume (PTV), and normal structures including the optic chiasm. Dose-volume histograms (DVHs) for the 3D CRT plans were then compared with those of the corresponding prospective IMRT plans. Both techniques maintained critical structure doses below tolerance levels while maintaining a minimum dose of 45 Gy to 100% of the PTV. While IMRT plans deliver consistently more heterogeneous dose distributions to the PTV, the median PTV dose is elevated in the IMRT plans compared with the 3D CRT plans. For critically located tumors like these pituitary macroadenomas, IMRT allows escalation of the median dose to the tumor without an accompanying loss in critical structure sparing or creating unacceptable cold spots within the PTV.

CD4+ T cell-induced differentiation of EBV-transformed lymphoblastoid cells is associated with diminished recognition by EBV-specific CD8+ cytotoxic T cells.

EBV transformation of human B cells in vitro results in establishment of immortalized cell lines (lymphoblastoid cell lines (LCL)) that express viral transformation-associated latent genes and exhibit a fixed, lymphoblastoid phenotype. In this report, we show that CD4(+) T cells can modify the differentiation state of EBV-transformed LCL. Coculture of LCL with EBV-specific CD4(+) T cells resulted in an altered phenotype, characterized by elevated CD38 expression and decreased proliferation rate. Relative to control LCL, the cocultured LCL were markedly less susceptible to lysis by EBV-specific CD8(+) CTL. In contrast, CD4(+) T cell-induced differentiation of LCL did not diminish sensitivity of LCL to lysis by CD8(+) CTL specific for an exogenously loaded peptide Ag or lysis by alloreactive CD8(+) CTL, suggesting that differentiation is not associated with intrinsic resistance to CD8(+) T cell cytotoxicity and that evasion of lysis is confined to EBV-specific CTL responses. CD4(+) T cell-induced differentiation of LCL and concomitant resistance of LCL to lysis by EBV-specific CD8(+) CTL were associated with reduced expression of viral latent genes. Finally, transwell cocultures, in which direct LCL-CD4(+) T cell contact was prevented, indicated a major role for CD4(+) T cell cytokines in the differentiation of LCL.

Novel target antigens for dendritic cell-based immunotherapy against ovarian cancer.

Identification of tumor-specific target antigens has been a major hurdle for the treatment of malignant disease by vaccination or immunotherapy. A second challenge has been the induction of therapeutically effective immune responses to these 'self' antigens. The recent recognition of dendritic cells as powerful antigen-presenting cells capable of inducing primary T-cell responses in vitro and in vivo--in combination with identification of tumor-specific antigens--has generated widespread interest in dendritic cell-based immunotherapy against a wide variety of tumors. In this review, a series of recently identified novel ovarian tumor antigens is discussed, and the potential for therapeutic dendritic cell vaccination targeted against these antigens is assessed.

Novel immunotherapeutic strategies in gynecologic oncology. Dendritic cell-based immunotherapy for ovarian cancer.

The recognition of tumor antigen loaded dendritic cells as one of the most promising approaches to induce a tumor specific immune response in vivo has recently generated widespread interest in the use of these natural adjuvants for the therapy of human malignancies refractory to standard treatment modalities. However, many cancer patients may not benefit from current strategies of cancer vaccination because an effective tumor antigen associated with their cancer has not yet been identified or because sufficient amounts of tumor tissue cannot be obtained for antigen preparation. The recent identification and cloning of a group of preferentially expressed serine proteases as novel ovarian tumor-associated antigens may offer the opportunity to test in a large group of patients the potential of DC-based immunotherapy. In this review, we describe these ovarian tumor antigens and assess the potential for therapeutic DC vaccination for the treatment of chemotherapy-resistant ovarian cancer.

Dosimetric evaluation of lung tumor immobilization using breath hold at deep inspiration.

PURPOSE: To examine the dosimetric benefit of self-gated radiotherapy at deep-inspiration breath hold (DIBH) in the treatment of patients with non-small-cell lung cancer (NSCLC). The relative contributions of tumor immobilization at breath hold (BH) and increased lung volume at deep inspiration (DI) in sparing high-dose lung irradiation (> or = 20 Gy) were examined. METHODS AND MATERIALS: Ten consecutive patients undergoing radiotherapy for Stage I-IIIB NSCLC who met the screening criteria were entered on this study. Patients were instructed to BH at DI without the use of external monitors or breath-holding devices (self-gating). Computed tomography (CT) scans of the thorax were performed during free breathing (FB) and DIBH. Fluoroscopy screened for reproducible tumor position throughout DIBH, and determined the maximum superior-inferior (SI) tumor motion during both FB and DIBH. Margins used to define the planning target volume (PTV) from the clinical target volume included 1 cm for setup error and organ motion, plus an additional SI margin for tumor motion, as determined from fluoroscopy. Three conformal treatment plans were then generated for each patient, one from the FB scan with FB PTV margins, a second from the DIBH scan with FB PTV margins, and a third from the DIBH scan with DIBH PTV margins. The percent of total lung volume receiving > or = 20 Gy (using a prescription dose of 70.9 Gy to isocenter) was determined for each plan. RESULTS: Self-gating at DIBH was possible for 8 of the 10 patients; 2 patients were excluded, because they were not able to perform a reproducible DIBH. For these 8 patients, the median BH time was 23 (range, 19-52) s. The mean percent of total lung volume receiving > or = 20 Gy under FB conditions (FB scan with FB PTV margins) was 12.8%. With increased lung volume alone (DIBH scan with FB PTV margins), this was reduced to 11.0%, tending toward a significant decrease in lung irradiation over FB (p = 0.086). With both increased lung volume and tumor immobilization (DIBH scan with DIBH PTV margins), the mean percent lung volume receiving > or = 20 Gy was further reduced to 8.8%, a significant decrease in lung irradiation compared to FB (p = 0.011). Furthermore, at DIBH, the additional benefit provided by tumor immobilization (i.e., using DIBH instead of FB PTV margins) was also significant (p = 0.006). The relative contributions of tumor immobilization and increased lung volume toward reducing the percent total lung volume receiving > or = 20 Gy were patient specific; however, all 8 of the patients analyzed showed a dosimetric benefit with this DIBH technique. CONCLUSION: Compared to FB conditions, at DIBH the mean reduction in percent lung volume receiving > or = 20 Gy was 14.3% with the increase in lung volume alone, 22.1% with tumor immobilization alone, and 32.5% with the combined effect. The dosimetric benefit seen at DIBH was patient specific, and due to both the increased lung volume seen at DI and the PTV margin reduction seen with tumor immobilization.

Androgen-accelerated bone maturation in mice is not attenuated by Faslodex, an estrogen receptor blocker.

Androgens accelerate bone maturation, but it is unclear to what extent this process may be mediated by estrogens derived from aromatization of androgens. In this study, we investigated whether an estrogen-blocking agent, Faslodex (ICI 182,780), can attenuate testosterone-accelerated skeletal maturation in immature mice. On days of life 2-8, mouse pups received either testosterone propionate (50 microg/100 g body weight), Faslodex (100 microg/100 g body weight), a combination of Faslodex + testosterone, or vehicle alone. Skeletal maturation was assessed in the forepaw and the lumbar spine. Testosterone caused acceleration of bone maturation (p < 0.05, compared with vehicle), predominantly of axial bones. Faslodex, however, failed to block the effect of testosterone, such that the mice receiving Faslodex + testosterone had skeletal maturation scores similar to those treated with testosterone alone. These results suggest that androgens have the capacity to stimulate bone maturation directly, probably via their own receptors.

Therapy for 6.5-7.5 years with recombinant insulin-like growth factor I in children with growth hormone insensitivity syndrome: a clinical research center study.

Eight children with GH insensitivity syndrome were treated with recombinant human insulin-like growth factor I (IGF-I) (80--120 microg/kg sc twice daily) for 6.5--7.5 yr. We previously reported that height velocity (HV) improved with treatment (from mean pretreatment HV of 4.0 cm/yr), to 9.3 cm/yr for the first year and 6.2 cm/yr for the second year. HV remained slightly below this during the subsequent years (mean HV: 5.4, 5.5, 5.2, and 4.8 cm/yr during years 3--6). Mean height SD score before therapy was -5.6; and it improved to -4.5, -4.4, and -4.2 after 2, 4, and 6 yr of therapy, respectively. Treatment was accompanied by gain in body weight and fat. Bone age advanced normally in the prepubertal patients, but it advanced more rapidly during the latter years of treatment in those patients undergoing pubertal changes. The growth of spleen and kidneys (determined by ultrasound) was rapid in the first 2--3 yr of therapy. More age- appropriate growth ensued, but six patients had a renal length for height more than 2 SD above the mean at 6--7 yr of treatment. No major adverse changes in biochemical profile were observed. IGF-I-related hypoglycemia occurred early in treatment with the younger patients, but this problem abated as treatment was continued. IGF-I therapy is effective in promoting statural growth in GH insensitivity syndrome patients, but the growth response is neither as intense nor as well-sustained as the growth response to GH among children with GH deficiency.

Gain of 1q is associated with adverse outcome in favorable histology Wilms' tumors.

Although several genes/genetic loci involved in the etiology of Wilms' tumor have been identified, little is known of the molecular changes associated with relapse. We therefore undertook an analysis by comparative genomic hybridization (CGH) of 58 tumor samples of favorable histology Wilms' tumor taken at initial diagnosis and/or relapse. Tumors with anaplastic histology were excluded as this is known to be associated with p53 mutation and a poor prognosis. A control group of 21 Wilms' tumors that did not relapse was also analyzed. The overall frequency of gains or losses of genetic material detected by CGH was similar in both groups (77% in relapsing tumors and 70% in the nonrelapse group) as was the median number of changes per tumor (relapse group: n = 4, range, 1 to 19; nonrelapse group: n = 3, range, 1 to 8). However, gain of 1q was significantly more frequent in the relapse series [27 of 46 (59%) versus 5 of 21 (24%), P: = 0.019]. In 12 matched tumor pairs, the CGH profiles, including 1q gain, were similar at diagnosis and relapse, with little evidence for further copy number changes being involved in clonal evolution. The results suggest that 1q gain at diagnosis could be used to identify patients with favorable histology Wilms' tumor at increased risk of relapse who might benefit from early treatment intensification.

Increased expression of protease M in ovarian tumors.

Proteases are known to play important roles in tumor invasion and metastasis. Protease M, which was originally identified by Anisowicz and colleagues in 1996, is a new member of the serine protease family. We also identified the protease M transcript in a differential PCR screen of ovarian tumors and have investigated its expression in 44 ovarian tumors (12 low malignant potential tumors, 32 carcinomas) and 10 normal ovaries using quantitative PCR. The PCR product was labeled with (32)P and a phosphoimager was used to determine the relative expression of the protease M gene compared to internal control beta-tubulin. mRNA expression levels of protease M were significantly elevated in 9 of 12 low malignant potential tumors and 30 of 32 carcinomas. Northern blot hybridization showed that the 1.7-kb protease M transcript was abundant in carcinoma but not detected in normal ovary. Immunohistochemical staining of normal ovary and ovarian tumor tissue sections with antibodies generated to protease M derived peptides corroborated the semi-quantitative PCR and Northern analysis data. Our results suggest that protease M is frequently overexpressed in ovarian tumors and may therefore contribute to the invasive nature or growth capacity of ovarian carcinomas.

Ovarian tumor cells express a transmembrane serine protease: a potential candidate for early diagnosis and therapeutic intervention.

Proteases have been implicated in the extracellular modulation required for tumor growth and invasion. In an effort to categorize those proteases contributing to ovarian carcinoma progression, we have utilized redundant primers to conserved amino acid (AA) domains surrounding the catalytic triad of His, Asp and Ser to amplify serine proteases that are differentially expressed in carcinomas. Using this method, we have identified and cloned a serine protease named TADG-15 (tumor-associated differentially expressed gene 15) that is overexpressed in ovarian tumors. TADG-15 is a transmembrane multidomain serine protease which includes ligand binding domains and a serine protease in the extracellular space.

Living with rheumatoid arthritis: the role of daily spirituality and daily religious and spiritual coping.

The objective of this preliminary study was to evaluate more fully the role of daily spiritual experiences and daily religious/spiritual coping in the experience of individuals with pain due to rheumatoid arthritis (RA). Thirty-five individuals with RA were asked to keep a structured daily diary for 30 consecutive days. The diary included standardized measures designed to assess spiritual experiences, religious and spiritual pain coping, salience of religion in coping, religious/spiritual coping efficacy, pain, mood, and perceived social support. The participants in this study reported having spiritual experiences, such as feeling touched by the beauty of creation or feeling a desire to be closer or in union with God, on a relatively frequent basis. These participants also reported using positive religious and spiritual coping strategies much more frequently than negative religious and spiritual coping strategies. Although most of the variance in these measures was due to differences between persons, each measure also displayed a significant variability in scores from day to day. Indeed, there was just as much (or more) variability in these measures over time as there was variability in pain. Individuals who reported frequent daily spiritual experiences had higher levels of positive mood, lower levels of daily negative mood, and higher levels of each of the social support domains. Individuals who reported that religion was very salient in their coping with pain reported much higher levels of instrumental, emotional, arthritis-related, and general social support. Coping efficacy was significantly related to pain, mood, and social support in that on days that participants rated their ability to control pain and decrease pain using spiritual/religious coping methods as high, they were much less likely to have joint pain and negative mood and much more likely to have positive mood and higher levels of general social support. Taken together, these results suggest that daily spiritual experiences and daily religious/spiritual coping variables are important in understanding the experience of persons who have RA. They also suggest that newly developed daily diary methods may provide a useful methodology for studying religious and spiritual dimensions of living with arthritis.

The CA 125 gene: an extracellular superstructure dominated by repeat sequences.

CA 125 has long presented problems to both clinicians and investigators because there was no definitive information on its structure and function. Here, we describe our work on cloning the CA 125 gene with the anticipation that such information will provide the basis for understanding its structure and its physiologic role in both normal and malignant tissues. The CA 125 protein core is composed of a short cytoplasmic tail, a transmembrane domain and an extraordinarily large glycosylated extracellular structure. This structure is dominated by a repeat domain composed of 156 amino acid repeat units which encompass the epitope binding sites. The molecule also includes an amino terminal domain of serine/threonine-rich sequences which would account for most of the O-glycosylation known to be present in CA 125. CA 125 is an unusually large transmembrane glycoprotein. Its release from the surface of the cell is most probably dependent on cytoplasmic phosphorylation followed by proteolytic cleavage. The extracellular domain is characterized by a large number of repeat units (probably 60+) which encompass an interactive disulfide bridged cysteine-loop and the site of OC125 and M11 binding. Sequencing the gene provides us with the ability to initiate the quest to understand the biological function of CA 125.

Expression of the protease inhibitor antileukoprotease and the serine protease stratum corneum chymotryptic enzyme (SCCE) is coordinated in ovarian tumors.

We have previously reported that the stratum corneum chymotryptic enzyme (SCCE) is overexpressed in ovarian cancers and that SCCE has potential as a useful marker and/or a therapeutic target for ovarian carcinoma. Antileukoprotease (ALP) has been shown to be a specific inhibitor of SCCE. The objective of this study was to investigate the potential cotranscription and overexpression of ALP in carcinoma of the ovary. The expression of ALP transcript was evaluated by Northern blot hybridization and by semiquantitative polymerase chain reaction (PCR) technique. The presence of the ALP protein in ovarian tumor cells was evaluated by immunohistochemistry. Northern blot hybridization showed that the ALP transcript was abundant in ovarian carcinomas but was not detected in the normal ovary. Semi-quantitative PCR examination revealed that the mRNA level of ALP was significantly elevated in low-malignant-potential tumors and in ovarian carcinomas compared with that in normal ovaries (P < 0.01). There was significant positive correlation between SCCE and ALP mRNA overexpression status in ovarian tumor cases (P < 0.01). Immunohistochemical expression of ALP protein was observed in ovarian tumor cells, whereas little or no staining was observed in normal ovarian surface epithelium. Like SCCE, ALP is highly overexpressed in ovarian tumor cells, which begs the question of whether it remains an effective inhibitor of SCCE or whether it is discordant in time or space and is ineffective as an inhibitor of the SCCE enzyme.