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Biomedical subjects

J Wing

Publications and source records attributed to J Wing.

At least 19 recordsLinked to original sources

Two-year effects of alendronate on bone mineral density and vertebral fracture in patients receiving glucocorticoids: a randomized, double-blind, placebo-controlled extension trial.

OBJECTIVE: To evaluate the continued efficacy and safety of alendronate (ALN) for up to 2 years in patients receiving glucocorticoids. METHODS: This is a 12-month extension of a previously completed 1-year trial of daily ALN, performed to evaluate the effects of ALN over a total of 2 years in 66 men and 142 women continuing to receive at least 7.5 mg of prednisone or equivalent daily. All patients received supplemental calcium and vitamin D. The primary end point was the mean percentage change in lumbar spine bone mineral density (BMD) from baseline to 24 months. Other outcomes included changes in hip and total body BMD, biochemical markers of bone turnover, radiographic joint damage of the hands, and vertebral fracture incidence. RESULTS: The mean (+/-SEM) lumbar spine BMD increased by 2.8 +/- 0.6%, 3.9 +/- 0.7%, and 3.7 +/- 0.6%, respectively, in the groups that received 5 mg, 10 mg, and 2.5/10 mg of ALN daily (P < or = 0.001) and decreased by -0.8 +/- 0.6% in the placebo group (P not significant) over 24 months. In patients receiving any dose of ALN, BMD was increased at the trochanter (P < or = 0.05) and maintained at the femoral neck. Total body BMD was increased in patients receiving 5 or 10 mg ALN (P < or = 0.01). These 2 dose levels of ALN were more effective than placebo at all sites (P < or = 0.05). Bone turnover markers (N-telopeptides of type I collagen and bone-specific alkaline phosphatase) decreased 60% and 25%, respectively, during treatment with ALN (P < or = 0.05). There were fewer patients with new vertebral fractures in the ALN group versus the placebo group (0.7% versus 6.8%; P = 0.026). The safety profile was similar between treatment groups. CONCLUSION: Alendronate is an effective, well-tolerated therapy for the prevention and treatment of glucocorticoid-induced osteoporosis, with sustained treatment advantages for up to 2 years.

Adult↗

Molecular analysis of the anthocyanin2 gene of petunia and its role in the evolution of flower color.

The shape and color of flowers are important for plant reproduction because they attract pollinators such as insects and birds. Therefore, it is thought that alterations in these traits may result in the attraction of different pollinators, genetic isolation, and ultimately, (sympatric) speciation. Petunia integrifolia and P. axillaris bear flowers with different shapes and colors that appear to be visited by different insects. The anthocyanin2 (an2) locus, a regulator of the anthocyanin biosynthetic pathway, is the main determinant of color differences. Here, we report an analysis of molecular events at the an2 locus that occur during Petunia spp evolution. We isolated an2 by transposon tagging and found that it encodes a MYB domain protein, indicating that it is a transcription factor. Analysis of P. axillaris subspecies with white flowers showed that they contain an2(-) alleles with two alternative frameshifts at one site, apparently caused by the insertion and subsequent excision of a transposon. A third an2(-) allele has a nonsense mutation elsewhere, indicating that it arose independently. The distribution of polymorphisms in an2(-) alleles suggests that the loss of an2 function and the consequent changes in floral color were not the primary cause for genetic separation of P. integrifolia and P. axillaris. Rather, they were events that occurred late in the speciation process, possibly to reinforce genetic isolation and complete speciation.

Alleles↗

Brief scale for measuring the outcomes of emotional and behavioural disorders in children. Health of the Nation Outcome Scales for children and Adolescents (HoNOSCA).

BACKGROUND: Following the development of a child and adolescent version of the Health of the Nation Outcome Scales (HoNOSCA), field trials were conducted to assess their feasibility and acceptability in routine outcome measurement. AIMS: To evaluate the reliability, validity and acceptability of HoNOSCA in routine outcome measurement. METHOD: Following training, 36 field sites provided ratings on 1276 cases at one time point and outcome data on 906. Acceptability was assessed by way of written feedback and at a debriefing meeting. RESULTS: HoNOSCA demonstrated satisfactory reliability and validity characteristics. It was sensitive to change and its ability to measure change accorded with the clinicians' independent rating. HoNOSCA was reasonably acceptable to clinicians' from a range of disciplines and services. CONCLUSIONS: Provided that training needs can be met, HoNOSCA represents a satisfactory brief outcome measure which could be used routinely in child and adolescent mental health services.

Child↗

Health of the Nation Outcome Scales for elderly people (HoNOS 65+).

BACKGROUND: Health of the Nation Outcome Scales (HoNOS) have been developed to measure of outcomes in people with mental health problems. AIMS: The particular physical and cognitive problems affecting older people requires a specific scale for their measurement. We describe the development of such a scale, named HoNOS 65+. METHOD: Pilot, validity and reliability studies were carried out on an amended scale. Validity was assessed by comparison with existing scales reflecting depression, cognitive function, psychiatric symptomatology, activities of daily living and functional abilities. Reliability was measured in two centres. RESULTS: HoNOS 65+ was successfully amended to include specific aspects of mental health problems in older people including the phenomenology of depression, delusions occurring in the presence of dementia, incontinence and agitation/restlessness. HoNOS 65+ was able to discriminate between people suffering from organic and functional illnesses. Correlations with other scales indicated reasonable validity. Reliability was satisfactory. CONCLUSIONS: Aversion of HoNOS 65+ is presented (see pp. 435-438, this issue) which is appropriate for use in elderly people with mental health problems.

Activities of Daily Living↗

A novel human prostate-specific, androgen-regulated homeobox gene (NKX3.1) that maps to 8p21, a region frequently deleted in prostate cancer.

We have isolated a prostate-specific gene (NKX3.1) in humans that is homologous to the Drosophila NK homeobox gene family. Northern blot analyses indicate that this gene is expressed at high levels in adult prostate and at a much lower level in testis, but is expressed little or not at all in several other tissues. In an androgen-dependent prostate carcinoma line, LNCaP, NKX3.1 mRNA is expressed at a basal level that was increased markedly upon androgen stimulation; the NKX3.1 mRNA was undetectable in several other human tumor cell lines including two androgen-independent prostate carcinoma lines. The NKX3.1 gene maps to chromosome band 8p21, a region frequently reported to undergo a loss of heterozygosity associated with tissue dedifferentiation and loss of androgen responsiveness during the progression of prostate cancer. Based on these data we propose that NKX3.1 is a candidate gene for playing a role in the opposing processes of androgen-driven differentiation of prostatic tissue and loss of that differentiation during the progression of prostate cancer.

Adult↗

SCAN and the PSE tradition.

The development of a series of instruments that has so far culminated in SCAN version 2.0 began in the late 1950s because of the need for better tools for clinical measurement (including categorization and diagnosis). The basic principles of the PSE had long been decided by the time of first publication in 1974 and have remained the same since. Based on the glossary of differential definitions, the aim is to provide comprehensive, accurate and technically specifiable means of describing and classifying clinical phenomena in order to make comparisons. Insofar as it fulfils this aim, SCAN can be used to enhance clinical work and education and advance knowledge through its use in biomedical, epidemiological and psychosocial research.

Cross-Cultural Comparison↗

Developmental expression of a candidate müllerian inhibiting substance type II receptor.

We have isolated a candidate Müllerian inhibiting substance (MIS) type II receptor complementary DNA from an embryonic rat urogenital ridge library and have studied its binding to MIS, its developmental pattern of expression and tissue distribution. By in situ hybridization with a full-length riboprobe, the receptor is expressed in the mesenchymal cells surrounding the Müllerian duct at embryonic days 14, 15, and 16 and in tubular and follicular structures of the rat fetal gonads. Expression of the messenger RNA was also seen in the granules cells and seminiferous tubules of pubertal gonads. Northern analysis revealed that the MIS type II receptor messenger RNA is highly expressed in embryonic, pubertal, and adult testes and ovaries, as well as in the gravid uterus. The timing of expression in the gonads of both sexes was also analyzed by Northern analyses that showed high levels of expression at the time of Müllerian duct regression, much lower levels neonatally and prepubertally and then increased expression again with sexual maturation. The tissue and developmental specificity of expression of this receptor, which make it likely that this is the functional MIS type II receptor, can be used to advantage in therapeutic targeting strategies and to decipher the function of MIS in the gonads.

Aging↗

Targeted gene inactivation in petunia by PCR-based selection of transposon insertion mutants.

Establishment of loss-of-function phenotypes is often a key step in determining the biological function of a gene. We describe a procedure to obtain mutant petunia plants in which a specific gene with known sequence is inactivated by the transposable element dTph1. Leaves are collected from batches of 1000 plants with highly active dTph1 elements, pooled according to a three-dimensional matrix, and screened by PCR using a transposon- and a gene-specific primer. In this way individual plants with a dTph1 insertion can be identified by analysis of about 30 PCRs. We found insertion alleles for various genes at a frequency of about 1 in 1000 plants. The plant population can be preserved by selfing all the plants, so that it can be screened for insertions in many genes over a prolonged period.

Alleles↗

A national audit of new long-stay psychiatric patients. I: Method and description of the cohort.

BACKGROUND: This first report of a national audit of new long-stay (NLS) psychiatric patients conducted in 1992 describes the survey method and characteristics of the cohort. METHOD: Psychiatrists from 59 UK mental health services returned data on 905 patients, aged 18-64 on admission, who had been in hospital for between six months and three years. RESULTS: Two particular sub-groups were observed. Younger NLS patients (aged 18-34) were predominantly single men with schizophrenia; 43% of these had a history of serious violence, dangerous behaviour or admission to a Special Hospital and over one-third were formally detained. Older NLS patients (aged 55-67) were predominantly married or previously married women, more often with a diagnosis of affective disorder or dementia and with poor personal and social functioning; over half were at moderate or severe risk of non-deliberate self-harm. CONCLUSIONS: Despite the continued policy of bed closures and focus on care in the community, some patients admitted recently to psychiatric units in the UK still have protracted hospital stays.

Adolescent↗

A national audit of new long-stay psychiatric patients. II: Impact on services.

BACKGROUND: This second report of a national audit of new long-stay (NLS) psychiatric patients describes the services caring for the patients and the reasons why patients were still in hospital. METHOD: Data analyses addressed the prevalence of NLS patients, the residential resources available to services, the distributions of patients within services, clinicians' views as to the appropriateness of current placement and the reasons for any inappropriate placements. RESULTS: The average point prevalence was 6.1 per 100,000 population; it was significantly lower in England and Wales (5.6, s.d. = 3.2) than in Scotland and Northern Ireland (10.7, s.d. = 6.4, ANOVA F ratio = 10.9, P < 0.01). The estimated rate of accumulation was 1.3 per 100,000 population per year. Many English services had very few non-acute psychiatric beds and 31% of English NLS patients, despite their protracted lengths of stay, were housed on acute wards. Assessors thought that 61% of patients would be better placed in a non-hospital setting; 47% were thought to require a community-based residential setting, and of these over one-half were still in hospital because no suitable community placement was available. CONCLUSIONS: Many NLS patients remain in hospital because their residential needs are not met by existing community provision.

Adolescent↗

Who pays for community care? The same old question.

Trends in mental health service funding over the past 40 years show that the programme of hospital closures has not resulted in a significant release of resources to fund community based services. Far from being excessive, the current provision of residential services (both NHS and non-NHS) for mentally ill people is now below levels recommended as sufficient by the government, the Royal College of Psychiatrists, and the National Schizophrenia Fellowship. What clinical research evidence there is suggests that more rather than fewer residential places are required. This situation is likely to be compounded by the recent transfer of responsibility for funding private and voluntary residential care from the Department of Social Security to local authority social services departments.

Community Mental Health Services↗

New findings on tardive dyskinesia in a community sample.

In a geographically defined area sample of 141 long-term psychiatric patients in day care in south London, the relationship between tardive dyskinesia (TD) and other aspects of illness, treatment, and social and psychological functioning were studied. The results are compared with previous findings. TD was significantly associated with parkinsonian symptoms and with the number of years in contact with the psychiatric services. There was a trend, in affective disorder only, towards an association with current neuroleptic dose. The patients with affective disorder also had higher rates of TD than patients with schizophrenia and paranoid psychosis. History of treatment with ECT correlated negatively with TD among those with schizophrenia, and positively among those with affective disorder. As in other studies, duration of neuroleptic treatment did not correlate with the presence or absence of TD. In contrast to some previous reports, age and cognitive status were not related to TD status. Possible reasons for this are discussed.

Aged↗

The acute effects of glucosidase inhibition on post-meal glucose increments in insulin-dependent diabetics.

The effects of glucosidase inhibition on postprandial glucose tolerance was studied in 11 insulin-dependent diabetics. In comparison with placebo, 50 mg miglitol was able to lower the incremental glucose response significantly at 30 minutes and 60 minutes when insulin was injected: (i) 30 minutes before the meal (2,3 +/- 0,5 mmol/l v. 0,37 +/- 0,2 mmol/l; P less than 0,001; and 5,0 +/- 0,7 mmol/l v. 1,1 +/- 0,8 mmol/l; P less than 0,001); and (ii) immediately before the meal (2,3 +/- 0,5 mmol/l v. 2,2 +/- 0,9 mmol/l; P less than 0,001) respectively. The incremental glucose area under the curve when insulin was injected 30 minutes before breakfast was also significantly reduced on miglitol in comparison with placebo (0,67 +/- 0,15 mmol/l v. 0,16 +/- 0,14 mmol/l; P less than 0,01). The effect of miglitol was more evident when insulin was injected 30 minutes before rather than immediately before the meal. No significant adverse effects were encountered. It is concluded that: (i) miglitol safely reduces the early post-meal glucose increments in insulin-dependent diabetics; and (ii) its effect enhances the hypoglycaemic response of an appropriately timed injection of insulin.

1-Deoxynojirimycin↗