RESUMEN

AIMS: To assess the impact of continual major National Health Service reorganization on commissioning, organizational and delivery arrangements for secondary care diabetes services. To explore how consultant diabetologists and diabetes specialist nurses perceive the issues facing diabetes specialist services in 2011 and how these have changed in the preceding decade. METHODS: We used a longitudinal case study approach that combined quantitative and qualitative methods. Five locations in England were purposively selected to represent the wider diabetes specialist community, and seven semi-structured interviews were conducted. Interviews were recorded, transcribed verbatim and analysed using Framework analysis. Findings were compared with and contrasted to results from national quantitative surveys of diabetes specialist services undertaken in 2000 and 2006. RESULTS: Clinicians viewed positively the expertise and commitment of multidisciplinary teams and their ability to adapt to new situations. Negative perceptions persisted throughout the decade, relating to the continual change that threatens to dismantle relationships and services which had taken many years to establish. Lack of resources, inadequate manpower planning and poor access to psychological support for people with diabetes remained constant themes from 2000 to 2011. CONCLUSIONS: A willingness to innovate and work differently to improve services was identified; however, clinicians must be supported through organizational changes to ensure people with diabetes receive high-quality care. The disruptive nature of organizational change was a recurrent theme throughout the decade. Periods of stability must exist within commissioning to allow relationships, which are key to integration, to be maintained and permit service improvements to develop.

Asunto(s)

RESUMEN

BACKGROUND: Previously, using gene-knockdown techniques together with genome expression array analysis, we showed the gene protein Kinase C (PKC)-zeta (PRKCZ) to mediate the malignant phenotype of human prostate cancer. However, according to NCBI, the gene has undergone several major iterations. Therefore, to understand the relationship between its structure and biological activities, we have analysed its expressed sequence in prostate cancer cell lines and tissues. METHODS: Transcriptome-walking and targeted PCR were used to sequence the mRNA transcribed from PRKCZ. Hydropathy analysis was employed to analyse the hypothetical protein sequence subsequently translated and to identify an appropriate epitope to generate a specific monoclonal antibody. RESULTS: A novel sequence was identified within the 3'-terminal domain of human PRKCZ that, in prostate cancer cell lines and tissues, is expressed during transcription and thereafter translated into protein (designated PKC-ζ(-PrC)) independent of conventional PKC-ζ(-a). The monoclonal antibody detected expression of this 96 kD protein only within malignant prostatic epithelium. INTERPRETATION: Transcription and translation of this gene sequence, including previous intronic sequences, generates a novel specific biomarker of human prostate cancer. The presence of catalytic domains characteristic of classic PKC-ß and atypical PKC-ι within PKC-ζ(-PrC) provides a potential mechanism for this PRKCZ variant to modulate the malignant prostatic phenotype out-with normal cell-regulatory control.

Asunto(s)

RESUMEN

The main aims were to ascertain the progress made in the implementation of retinal screening services and to explore any barriers or difficulties faced by the programmes. The survey focused on all the essential elements for retinal screening, including assessment and treatment of screen-positive cases. Eighty-five per cent of screening programmes have a coordinated screening service and 73% of these felt that they have made significant progress. Eighty-five per cent of screening units use 'call and recall' for appointments and 73.5% of programmes follow the National Screening Committee (NSC) guidance. Although many units worked closely with ophthalmology, further assessment and management of screen-positive patients was a cause for concern. The fast-track referral system, to ensure timely and appropriate care, has been difficult to engineer by several programmes. This is demonstrated by 48% of programmes having waiting lists for patients identified as needing further assessment and treatment for retinopathy. Ophthalmology service for people with diabetic retinopathy was provided by a dedicated ophthalmologist in 89.4% of the programmes. Sixty-six per cent of the programmes reported inadequate resources to sustain a high-quality service, while 26% highlighted the lack of infrastructure and 49% lacked information technology (IT) support. In conclusion, progress has been made towards establishing a national screening programme for diabetic retinopathy by individual screening units, with a number of programmes providing a structured retinal screening service. However, programmes face difficulties with resource allocation and compliance with Quality Assurance (QA) standards, especially those which apply to ophthalmology and IT support. Screening programmes need to be resourced adequately to ensure comprehensive coverage and compliance with QA.

Asunto(s)

RESUMEN

AIMS: To review the working practices of UK diabetes specialist nurses (DSNs), specific clinical roles, and to examine changes since 2000. METHODS: Postal questionnaires were sent to lead DSNs from all identifiable UK diabetes centres (n = 361). Quantitative and qualitative data were collected on the specific clinical roles, employment, and continual professional development of hospital and community DSNs, Nurse Consultants and Diabetes Healthcare Assistants. RESULTS: 159 centres (44%) returned questionnaires. 78% and 76% of DSNs plan and deliver education sessions compared with 13% in 2000 with a wider range of topics and with less input from medical staff. 22% of DSNs have a formal role in diabetes research compared with 48% in 2000. 49% of Hospital DSNs, 56% of Community DSNs and 66% of Nurse Consultants are involved in prescribing. 55% of DSNs carry out pump training, 72% participate in ante-natal and 27% renal clinics. 90% of services have independent diabetes nurse-led clinics. 93% of services have a dedicated Paediatric DSN. The mean number of children under the care of each PDSN is 109 (mode 120), which exceeds Royal College of Nursing recommendations. 48% of DSNs have protected time for continuing professional development of staff and 15% have a protected budget. One third of DSNs are on short-term contracts funded by external sources. CONCLUSIONS: The DSN role has evolved since 2000 to include complex service provision and responsibilities including specialist clinics, education of healthcare professionals and patients. The lack of substantive contracts and protected study leave may compromise these roles in the future.

Asunto(s)

RESUMEN

AIMS: To assess the availability and types of psychological services for people with diabetes in the UK, compliance with national guidelines and skills of the diabetes team in, and attitudes towards, psychological aspects of diabetes management. METHODS: Postal questionnaires to team leads (doctor and nurse) of all UK diabetes centres (n = 464) followed by semi-structured telephone interviews of expert providers of psychological services identified by team leads. RESULTS: Two hundred and sixty-seven centres (58%) returned postal questionnaires; 66 (25%) identified a named expert provider of psychological services, of whom 53 (80%) were interviewed by telephone. Less than one-third (n = 84) of responding centres had access to specialist psychological services and availability varied across the four UK nations (P = 0.02). Over two-thirds (n = 182) of centres had not implemented the majority of national guidelines and only 2.6% met all guidelines. Psychological input into teams was associated with improved training in psychological issues for team members (P < 0.001), perception of better skills in managing more complex psychological issues (P < or = 0.01) and increased likelihood of having psychological care pathways (P < or = 0.05). Most (81%) expert providers interviewed by telephone were under-resourced to meet the psychological needs of their population. CONCLUSIONS: Expert psychological support is not available to the majority of diabetes centres and significant geographical variation indicates inequity of service provision. Only a minority of centres meet national guidelines. Skills and services within diabetes teams vary widely and are positively influenced by the presence of expert providers of psychological care. Lack of resources are a barrier to service provision.

Asunto(s)

RESUMEN

AIMS: To identify the views and working practices of consultant diabetologists in the UK in 2006-2007, the current provision of specialist services, and to examine changes since 2000. METHODS: All 592 UK consultant diabetologists were invited to participate in an on-line survey. Quantitative and qualitative analyses of responses were undertaken. A composite 'well-resourced service score' was calculated. In addition to an analysis of all respondents, a sub-analysis was undertaken, comparing localities represented both in 2006/2007 and in 2000. RESULTS: In 2006/2007, a 49% response rate was achieved, representing 50% of acute National Health Service Trusts. Staffing levels had improved, but remained below recommendations made in 2000. Ten percent of specialist services were still provided by single-handed consultants, especially in Northern Ireland (in 50% of responses, P = 0.001 vs. other nations). Antenatal, joint adult-paediatric and ophthalmology sub-specialist diabetes services and availability of biochemical tests had improved since 2000, but access to psychology services had declined. Almost 90% of consultants had no clinical engagement in providing community diabetes services. The 'well-resourced service score' had not improved since 2000. There was continued evidence of disparity in resources between the nations (lowest in Wales and Northern Ireland, P = 0.007), between regions in England (lowest in the East Midlands and the Eastern regions, P = 0.028), and in centres with a single-handed consultant service (P = 0.001). Job satisfaction correlated with well-resourced service score (P = 0.001). The main concerns and threats to specialist services were deficiencies in psychology access, inadequate staffing, lack of progress in commissioning, and the detrimental impact of central policy on specialist services. CONCLUSIONS: There are continued disparities in specialist service provision. Without effective commissioning and adequate specialist team staffing, integrated diabetes care will remain unattainable in many regions, regardless of reconfigurations and alternative service models.

Asunto(s)

RESUMEN

BACKGROUND: Amniocentesis test results are usually available only after 18 weeks gestation. Chorion villus sampling (CVS) may be performed transabdominally or transvaginally, usually between 10 and 12 weeks gestation. OBJECTIVES: The objective of this review was to assess the safety and accuracy of chorion villus sampling compared to amniocentesis. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register. SELECTION CRITERIA: Randomised trials comparing first trimester chorion villus sampling and second trimester amniocentesis. DATA COLLECTION AND ANALYSIS: Trial quality was assessed. MAIN RESULTS: Three studies involving over 9000 women were included. The trials were generally of good quality. Compared to amniocentesis, chorion villus sampling was associated with more sampling and technical failures, and more false positive and false negative results. Pregnancy loss was more common after chorion villus sampling (odds ratio 1.33, 95% confidence interval 1.17 to 1.52). There is a suggestion (though not statistically significant) of an increase in stillbirths and neonatal deaths following chorion villus sampling. Maternal complications were uncommon. REVIEWER'S CONCLUSIONS: The increase in miscarriages after chorion villus sampling compared to amniocentesis appear to be procedure related. Second trimester amniocentesis appears to be safer than chorion villus sampling. The benefits of earlier diagnosis with chorion villus sampling must be set against the greater risk of pregnancy loss.

Asunto(s)

RESUMEN

BACKGROUND/PURPOSE: Interstitial cells of Cajal (ICC) recently have been identified as intestinal pacemaker cells. Abnormalities in ICC are increasingly recognized in a number of neonatal disorders such as infantile hypertrophic pyloric stenosis, Hirschsprung's disease, and transient intestinal pseudo-obstruction. The aim of this study was to determine the fetal and postnatal differentiation and development of ICC in the human gastrointestinal tract to aid interpretation of pathological specimens. METHODS: Specimens of human gastrointestinal tract from (1) fetuses (9 to 17 weeks' gestation; n = 12), (2) premature and full-term neonates with non-gut motility-related disorders, (age 26 to 59 weeks' gestation; n = 13), and (3) children (age 4 months to 13 years; n = 7) were immunohistochemically stained with antibodies to c-kit(a marker for ICC) and protein gene product 9.5 (PGP9.5, a marker for neural tissue). RESULTS: (1) C-kit-positive ICC were present throughout the gut in all specimens including those from the earliest gestational ages. C-kit and PGP9.5 immunoreactivities were present in different cell populations. (2) The distribution of ICC varied with gestational age and with region of the gut. (3) Maturation of ICC networks continues postnatally in a region-specific manner. CONCLUSIONS: ICC are present from an early stage in human gut development. Interpretation of apparent abnormalities in ICC distribution as being of pathological significance should be tempered by the knowledge that ICC networks continue to develop postnatally and that ICC development varies throughout the gut.

Asunto(s)

RESUMEN

In adult life, the type 2 isozyme of 11beta-hydroxysteroid dehydrogenase (11betaHSD2) protects the mineralocorticoid receptor (MR) from glucocorticoid by inactivating cortisol to cortisone. 11betaHSD2 activity has been reported in human fetal tissues, where glucocorticoids may impair fetal growth yet are also required for normal fetal development. Using digoxigenin-labeled complementary ribonucleic acid (RNA) probes and an in-house 11betaHSD2 antiserum, we have analyzed the expression of 11betaHSD2, MR, and glucocorticoid receptor (GR) in human fetal tissues of gestational age 6-17 weeks (n=15). 11BetaHSD2 expression was absent at gestational age 6+ weeks, but was expressed in abundance in many fetal tissues between 8-12 weeks. At this time, 11betaHSD2 colocalized with GR messenger RNA (mRNA) expression in metanephros, gut, muscle, spinal cord and dorsal root ganglia, periderm, sex chords of testis, and adrenal. In particular within fetal kidney, intense expression of 11betaHSD2 and GR mRNA was observed over Bowman's capsule and the vascular tufts of developing glomeruli as they migrated from the surface of the kidney to the inner cortex. Only lung and adrenal medullary rests demonstrated high levels of GR mRNA but low levels of 11betaHSD2. 11BetaHSD2 mRNA and immunoreactivity staining patterns were similar, with the exception of the fetal adrenal, where mRNA was localized to the outer definitive zone but immunoreactivity was localized to the inner fetal zone. Colocalization of 11betaHSD2 (and GR mRNA) with MR mRNA was observed principally within epithelial cells of collecting ducts, particularly after 16 weeks gestation when the pattern of distribution of 11betaHSD2 became more adult in nature. High levels of MR mRNA were observed within developing bone. The data indicate that 11betaHSD2 in fetal life principally modulates ligand access to the GR in most fetal tissues, notably glomeruli and tubules in the developing kidney, testis, and periderm, and this may be have ramifications for fetal sodium homeostasis and differentiation. The development of tissues previously shown to have a critical requirement for glucocorticoids, such as lung and adrenal medulla, is facilitated by the expression of GR mRNA, but not 11betaHSD2. The expression of MR mRNA in high abundance in bone suggests a role for corticosteroids in human bone development, and the low/absent expression of 11betaHSD2 at this site suggests that it is functionally acting as a GR.

Asunto(s)

RESUMEN

PIP: The availability of new medical techniques for induced abortion in the first trimester enables observation of the incidence and nature of embryonic and fetal abnormalities in early pregnancy. 506 women, presenting to the Liverpool (England) Women's Hospital in 1994-96 for induced abortion before 9 weeks of gestation, were given oral mifepristone followed by oral misoprostol. Fetal tissue was collected from 206 (44%) of these women. Embryos that appeared structurally abnormal on macroscopic evaluation were examined histologically. There were 39 abnormal embryos, including 10 cases of neural tube defect and 6 abdominal wall defects, and a total of 72 potentially nonviable pregnancies. The potential loss rate for embryos with structural abnormalities or other nonviable conditions was 34%--higher than the widely cited 15% rate of spontaneous abortion for clinical pregnancies. The former figure is likely to reflect the true loss rate in early pregnancy.^ieng

Asunto(s)

RESUMEN

The genes involved in negative cell cycle regulation and familial tumour susceptibility including APC, BRCA, p53, RB, WT1 are unique and have no homologies with other genes. Our hypothesis suggests they originated from mating factor genes, which halted cell division in response to stress to generate genetic diversity by sexual mechanisms. Some have evolved principally by vertical transmission (mismatch repair), others by horizontal transmission via mobile elements, predominantly in oocytes. We demonstrate amplification in human extra-embryonic tissues in fetus and mother in implantation; in the developing fetus, differing tissue-specific patterns are seen, especially between testis and ovary. We suggest that the fetus is susceptible to maternal transmission of infections including CMV, malaria, trypanosomes, whose sequences occur within these genes. In head and neck cancers, we demonstrate specific patterns of loss or instability involving up to seven different TSG. We suggest mechanisms of tumourigenesis involve transposable elements and episome formation, leading to loss of negative cell cycle regulation and exit from G0.

Asunto(s)

RESUMEN

BACKGROUND: Amniocentesis test results are usually available only after 18 weeks gestation. Chorion villus sampling (CVS) may be performed transabdominally or transvaginally, usually between 10 and 12 weeks gestation. OBJECTIVES: The objective of this review was to assess the safety and accuracy of chorion villus sampling compared to amniocentesis. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register. SELECTION CRITERIA: Randomised trials comparing first trimester chorion villus sampling and second trimester amniocentesis. DATA COLLECTION AND ANALYSIS: Trial quality was assessed. MAIN RESULTS: Three studies involving over 9000 women were included. The trials were generally of good quality. Compared to amniocentesis, chorion villus sampling was associated with more sampling and technical failures, and more false positive and false negative results. Pregnancy loss was more common after chorion villus sampling (odds ratio 1.33, 95% confidence interval 1.17 to 1.52). There is a suggestion (though not statistically significant) of an increase in stillbirths and neonatal deaths following chorion villus sampling. Maternal complications were uncommon. AUTHORS' CONCLUSIONS: The increase in miscarriages after chorion villus sampling compared to amniocentesis appear to be procedure related. Second trimester amniocentesis appears to be safer than chorion villus sampling. The benefits of earlier diagnosis with chorion villus sampling must be set against the greater risk of pregnancy loss.

Asunto(s)

Asunto(s)

RESUMEN

Partial hydatidiform mole associated with live births is a rare condition. There are not enough cases in the literature to allow the assessment of comprehensive risks to be made and upon which management policies can be based. Several clinical dilemmas arise following diagnosis of a viable pregnancy associated with molar tissue. We present two cases demonstrating the problems and suggest management based on outcome and a review of the literature.

Asunto(s)

RESUMEN

An improved protocol has been developed for physical enrichment of cDNA sequences by hybridization to genomic DNA. When applied to microdissection recombinants derived from a translocation breakpoint region associated with inherited mental illness, a single cycle of the procedure permitted enriched cDNAs to be visualized directly by agarose gel electrophoresis. Hybridization screening of a library of clones derived from the enriched cDNAs, employing the genomic resource as a probe, led to the identification of six novel gene fragments. This general approach to the isolation of regionally encoded genes could be applied to any subchromosomal interval as a first step towards global transcription map construction.

Asunto(s)

RESUMEN

We describe the use of pooled, region-specific hybridisation probes to screen high-density replica filters of a human genome YAC library. The probes were derived by microdissection of an approximately 30-Mbp region subtending the translocation breakpoint on a der(1)(1;11)(q42.1;q14.3) chromosome. Of 70 microdissection clones used in pools of 4-10, 47 identified a total of 77 YAC recombinants, representing over 50% of the microdissected region. This strategy can easily be adapted to other poorly mapped subchromosomal regions of the human or other mammalian genomes and will provide a solid framework for detailed contig map constructions.

Asunto(s)

Asunto(s)

RESUMEN

We describe the generation of large-fragment microclone libraries from the chromosomal breakpoint of a reciprocal balanced translocation linked to schizophrenia. The abnormality was visible under the phase-contrast microscope, allowing direct dissection from unstained, unbanded metaphases. Two separate microdissection experiments yielded 443 and 672 recombinants, respectively. Following complete EcoRI digestion, inserts with an average size of 0.3 kb (range, 0.2-3 kb) were obtained in the first experiment and 1.5 kb (range, 0.15-6.5 kb) in the second. FISH analysis of pooled clones "painted" back onto the derivative chromosome and assignment of microclones to somatic cell hybrids confirmed the fidelity of the method. Microdissection of chromosome regions identified by karyotype rearrangements in unstained, unbanded metaphases is a potentially powerful tool for positional cloning.

Asunto(s)

RESUMEN

A family is presented with multiple cases of mild mental retardation, schizophrenia and other functional psychoses, progressive hearing loss, and retinitis pigmentosa (RP). It closely resembles a previously reported Finnish family. We suggest that the phenotypes are not associated in this family by chance, but define a novel syndrome which may be caused by a mutant allele at a single genetic locus.

Asunto(s)

RESUMEN

Variation in the phenotypic expression of Albright's hereditary osteodystrophy (AHO) determined by the parent of transmission, suggests that the human Gs alpha gene (GNAS1), in which mutations occur in AHO, may be under imprinted control. GNAS1 is also known to map to a chromosomal region (20q13.11) showing syntenic homology with the imprinted mouse region 2E1-2H3. To establish if GNAS1 is indeed imprinted, we have examined the parental origin of GNAS1 transcription in human fetal tissues. Of 75 fetuses genotyped, at gestational ages ranging from 6 to 13 weeks, 13 heterozygous for a FokI polymorphism in exon 5 of GNAS1 were identified whose mothers were homozygous for one or other allele. RNA from up to 10 different tissues from each fetus was analysed by RT-PCR. In all cases expression from both parental alleles was shown by FokI digestion of RT-PCR products and quantification of the resulting fragments. No tissue specific pattern of expression was discerned in these experiments. If genomic imprinting regulates the expression of the human GNAS1 gene, our data suggest that the effect must either be subtle and quantitative, or be confined to a small subset of specialised hormone responsive cells within the target tissues.

Asunto(s)