People with learning disabilities in 'out-of-area' residential placements: 1. Policy context.

BACKGROUND: A growing shortage of residential care for people with learning disabilities leads to placement funded by one authority in another authority's area. Such out-of-area placements are governed by guidance from different government departments in respect of different funding streams. METHOD: This paper presents an analysis of this guidance and shows that it is inconsistent and incomplete. RESULTS AND CONCLUSION: The guidance creates a framework of incentives for health and social services authorities that could lead to people being placed out-of-area against their own best interests, with negative consequences for them and for the 'receiving' authorities. A companion paper uses interview data to examine the reasons for and effects of out-of-area placement.

People with learning disabilities in 'out-of-area' residential placements: 2. Reasons for and effects of placement.

BACKGROUND: Official guidance on out-of-area placements creates incentives that could lead to people being placed against their own best interests, with negative consequences for them and for the 'receiving' authorities. METHOD: Information was collected for 30 people through interviews with them, their families, home managers and care managers. Interviews concerned resident needs, reasons for placement, the homes, care management arrangements, resident quality of life and social inclusion. Information on care standards was abstracted from official records. RESULTS: The main reasons for out-of-area placement were insufficient local services of acceptable quality, financial incentives and loss of family contact through prior institutionalization. The effects varied, with the most disabled people experiencing worst outcomes. Some aspects were worse than comparison studies (choice, community involvement, number of homes meeting all the national minimum standards), some were the same (participation, family visiting and other contact), and one was better (visits to families). Variation was also evident in the involvement of social services staff from the placing authority and in ease of access to local healthcare resources. CONCLUSIONS: Social services and health authorities should develop services locally that can support people with the full range of individual needs. Perverse incentives should be removed, perhaps by increasing the application of direct payments and personalized budgets.

Evidence for complex multigenic inheritance of radiation AML susceptibility in mice revealed using a surrogate phenotypic assay.

The mapping of genes which affect individual cancer risk is an important but complex challenge. A surrogate assay of susceptibility to radiation-induced acute myeloid leukaemia (AML) in the mouse based on chromosomal radiosensitivity has been developed and validated. This assay was applied to the mapping of radiation-induced AML risk modifier loci by association with microsatellite markers. A region on chromosome (chr) 18 with strong association is identified and confirmed by backcross analysis. Additional loci on chrs 8 and 13 show significant association. A key candidate gene Rbbp8 on chr18 is identified. Rbbp8 is shown to be upregulated in response to X-irradiation in the AML sensitive CBA strain but not AML resistant C57BL/6 strain. This study demonstrates the strength of utilizing surrogate endpoints of cancer susceptibility in the mapping of mouse loci and identifies additional loci that may affect radiation cancer risk.

The prevalence of asthma symptoms, bronchial hyperresponsiveness and atopy in New Zealand adults.

AIMS: To examine the prevalence of asthma symptoms, bronchial hyperresponsiveness (BHR) and atopy in a random population sample of New Zealand adults. METHODS: A random sample of 2004 adults, aged 20-44 years, in Hawkes Bay, Wellington and Christchurch, were selected from respondents to a one-page respiratory screening questionnaire and invited to take part in further testing. Subjects attending the testing centres' laboratories underwent a detailed respiratory symptom questionnaire, Phazet testing to eleven common allergens, blood samples for total and specific IgE, and measurement of bronchial hyperresponsiveness. Subjects who did not wish to participate were encouraged to complete the questionnaire by telephone. RESULTS: A participation rate of 67% (1257 of 1877 eligibles) was achieved. We found a high prevalence for all measures of asthma in the previous 12 months: wheezing was reported by 28.5%, waking with shortness of breath by 7.7%, a physician diagnosis of asthma by 15.9% and asthma medications were used by 8.5%. Bronchial hyperresponsiveness was found in 24.9%, atopy in 34.8% and elevated serum IgE levels in 30.5%. Asthma symptoms (in the past 12 months) and atopy decreased with increasing age, whereas bronchial hyperresponsiveness increased with age. Females reported higher prevalences of waking with coughing (45.9%), nasal allergies (43.5%) and skin allergies (48.8%) compared to males (30.5%, 31.9% and 37.0%, respectively). There were no significant regional differences. CONCLUSIONS: Asthma symptoms, bronchial hyperresponsiveness and atopy are all common in adult New Zealanders. Their prevalence is associated with age, gender and current smoking but there are no significant regional differences between Hawkes Bay, Wellington and Christchurch.

Unravelling the familial tendency to aneurysmal disease: popliteal aneurysm, hypertension and fibrillin genotype.

PURPOSE: To screen patients with abdominal aortic aneurysm for popliteal aneurysm and investigate cardiovascular and genetic risk factors associated with aneurysmal disease at more than one site (generalised aneurysmal disease). SUBJECTS, DESIGN AND SETTING: All patients referred to the Regional Vascular Surgical Service at Charing Cross Hospital with unruptured abdominal aortic aneurysm between 1989 and 1993 were screened for popliteal aneurysms, using ultrasonography. MAIN OUTCOME MEASURES: Palpation of a popliteal aneurysm or ultrasonographic detection of popliteal dilatation, where the ratio maximum popliteal fossa diameter/suprageniculate popliteal diameter was > or = 1.5, in relation to cardiovascular and genetic risk factors. RESULTS: Clinical examination detected popliteal aneurysms in only 11/232 patients (5%), but ultrasonography demonstrated the presence of popliteal aneurysm in a further 13 patients, 24/232 in total (10%). Multivariate regression identified four independent factors associated with popliteal dilatation disease: age (p = 0.046), height (p = 0.006), systolic hypertension (p = 0.037) and triglyceride concentration (p = 0.009). Generalised aneurysmal disease and systolic blood pressure were associated with polymorphic variation in the fibrillin-1 gene, but not with variations in the apolipoprotein B and type III collagen genes. CONCLUSIONS: Few patients with abdominal aortic aneurysm (10%) also have popliteal aneurysms: the risk of popliteal dilatation increases with age, height, systolic blood pressure, triglyceride concentration and fibrillin genotype. The strong interaction between fibrillin genotype and blood pressure may contribute to the familial tendency to aortic aneurysm.

Microsatellite analysis of recurrent chromosome 2 deletions in acute myeloid leukaemia induced by radiation in F1 hybrid mice.

Deletions and/or rearrangements involving one copy of chromosome 2 are consistent and early events in the development of murine acute myeloid leukaemia (AML) by radiation. More than 90% of AMLs induced in the CBA strain of mice express such cytogenetic alterations, with chromosome 2 breakpoints clustering in the C and F regions of the chromosome. In inbred mouse strains, the molecular resolution of these breakpoints is problematic. However, by using x-ray-induced AMLs in FI progeny of genetically divergent CBA/H x C57BI, it has been possible to show region-specific loss of heterozygosity (LOH) in genetically linked sets of chromosome 2 microsatellite alleles from one of the two parental chromosomes. In the majority of cases, an acceptable concordance was shown for AML chromosome 2 deletion, as defined by microsatellites and as revealed by G-band cytogenetics. A degree of breakpoint clustering was found, but the identification of a number of deletion types, based on the position of proximal and distal breakpoints as defined by microsatellite analysis, strongly supports a leukaemogenic mechanism involving gene deletion. No bias towards loss of CBA or C57BI alleles was observed, and the gender of AML-presenting animals did not appear to influence the parental origin of the deletions. A molecular map of chromosome 2 breakpoints has now been established in FI AMLs as a first step towards the molecular cloning of breakpoint sequences.

Development of an assay method for purine catabolic enzymes in the mouse and its adaptation for use on an autoanalyzer.

An assay method has been developed for the purine catabolic enzymes adenosylhomocysteinase, adenosine deaminase (ADA), purine-nucleoside phosphorylase (PNP), and urate oxidase in mice. The assay links H2O2 produced during purine catabolism to the production of a dye complex. The assay method has been developed for ADA and PNP in erythrocytes and for all four enzymes in liver. The assay is cheap, sensitive, and easy to perform. The dye complex absorbs in the visible range, negating the need for an expensive ultraviolet spectrophotometer and allowing the use of an autoanalyzer.

DNA strand breakage during physiological apoptosis of the embryonic chick lens: free 3' OH end single strand breaks do not accumulate even in the presence of a cation-independent deoxyribonuclease.

Epithelial cells from the lens equator differentiate into elongated fiber cells. In the final steps of differentiation, the chromatin appears quite condensed and chromatin breakdown into nucleosomes occurs. DNA breaks due to an endodeoxyribonuclease activity corresponding to at least two polypeptides of 30 and 40 kDa have been identified. To identify the nature and the developmental appearance of initial breaks, nick translation reaction was followed both biochemically and in situ in fiber and epithelial cells from chick embryonic lenses. There is no accumulation of single-strand breaks (SSB) with 3'OH ends in lens fiber cells during embryonic development. Such damage can be increased in these cells by treatment with DNAase I indicating the absence of an inhibitor of the nick translation reaction in fiber cells. However, there are indications of the presence of DNA breaks with blocked termini when the phosphatase activity of nuclease P1 is used. The presence of breaks is also indicated by the large amounts of (ADP-ribose)n found in lens fibers particularly at 11 days of embryonic development (E11) as ADP-ribosyl transferase binds to and is activated by DNA strand breaks. Incubation of lens cells in vitro, which causes nucleosomal fragmentation only in fiber cells, produces SSB with 3'OH ends in both epithelia and fibers. Incubation for short periods, observed in experiments in situ, induces SSB first in the central fiber nuclei, which are late in differentiation. This may indicate that these SSB play a physiological role. Long incubations produce larger numbers of SSB in epithelia than fibers. The SSB in the fibers may have been converted into double-strand breaks (D SB), seen as nucleosomal fragments, and therefore no longer act as substrates for nick translation. The nuclease activity responsible for SSB production is independent of divalent cations and could be implicated in lens terminal differentiation.

An audit and international comparison of asthma management in the emergency department.

AIMS: 1. To perform an audit of asthma management in the Christchurch Hospital emergency department during the period March 1987 to August 1988. 2. To compare management of asthma in Christchurch with other centres in New Zealand and the United Kingdom. 3. To compare markers of asthma severity on admission with other centres. METHODS: Details of all attendances by adults to the Christchurch Hospital emergency department with acute asthma during the above period were recorded on specially designed asthma treatment sheets. This data was compared with similar studies performed in Wellington (NZ) and Southampton and Leicester (UK). RESULTS: 759 cases were analysed. Most subjects were in the 15-25 year age group. 47% were taking inhaled corticosteroids at presentation. History taking was satisfactory according to guidelines operative at that time. Peak flow rate measurement at presentation was performed in 79% of cases, and in 67% of cases following treatment. Nebulised bronchodilators were given in 88% of cases and parenteral steroids given in 22%. 46% of cases were discharged home and of these 28% received a course of oral prednisone. All management decisions, except the decision to give oral steroids on discharge, showed a relationship to objective indices of asthma severity. CONCLUSION: Comparison with other centres shows that the treatment of acute asthma in Christchurch was of a similar standard. Severity of asthma on presentation, as measured by peak flow and pulse rates showed no difference between Christchurch and Southampton.

Colour-coded duplex ultrasonography in the selection of patients for endovascular surgery.

Endovascular surgery using angioplasty or atherectomy may potentially relieve the symptoms of claudicants with minimal morbidity, but results are best when short stenoses are treated. In this study, colour-coded duplex ultrasonography has been compared with angiography. In aortoiliac segments duplex examination had a sensitivity of 88 per cent and a specificity of 100 per cent; in femoropopliteal disease the sensitivity was 100 per cent and duplex scanning identified more disease than angiography. Subsequently, 73 symptomatic limbs with femoropopliteal disease were scanned to assess their suitability for endovascular surgery. Of these limbs, 27 (37 per cent) had suitable lesions and the remaining 46 (63 per cent) were spared angiography. Colour-coded duplex ultrasonography can reliably be used to select patients for endovascular surgery.

Confirmation of assignment of the bovine K-casein locus by PCR.

The provision of a bovine gene map will allow the ready identification of genetic disease in cattle and will lead to the identification of the genetic loci responsible for quantitative traits of economic importance. An extension of the polymerase chain reaction to the identification of linkage in bovine-Chinese hamster cell hybrids has improved the speed and facility of the assignment of genes to linkage groups and thus makes it easier to achieve a bovine linkage map.

Adenosine deaminase, Ada, is in mouse chromosome 2H3, and is not allelic with wasted, wst.

The adenosine deaminase locus (Ada) in the mouse has been localized by in situ hybridization to band 2H3. Linkage analysis of backcross data has shown that Ada is 13.8 +/- 2.7 cM from the coat texture mutant, ragged, Ra. From the results of earlier work (Abbott, C. M., et al., Proc. Natl. Acad. Sci. USA 83:693, 1986), it had been suggested that wst was a low-activity allele of Ada, but this cannot be so because Ada and wst have been found to be nonallelic.

Analysis of polymorphism in the bovine casein genes by use of the polymerase chain reaction.

Methods have been devised for detecting polymorphisms in the bovine beta- and kappa-casein genes using the polymerase chain reaction (PCR) followed either by restriction enzyme digestion (to reveal a restriction fragment length polymorphism (RFLP] or by hybridization of an allele-specific oligonucleotide. These methods, as well as being faster and more sensitive than traditional RFLP methods, are of more general applicability since they can detect any change in DNA sequence. They require only a small sample of blood or semen and are applicable to animals of any age or sex. These methods make possible large-scale screening and thus selection for alleles at these loci. Typing of blood DNA can give erroneous results when the animal concerned is a twin; however, this can be overcome by retesting using milk or semen. Analysis of the kappa-casein genotype of Holstein-Friesian bulls gives frequencies for the A and B alleles of 0.80 and 0.20 respectively. Selection in favour of the B allele, which is superior for cheese production, could thus have a large effect. The A3 and B alleles at the beta-casein locus have been shown to be rare in the Holstein-Friesian population. Linkage disequilibrium exists between beta-casein B and kappa-casein B.

Mortality and increasing drug use in Edinburgh: implications for HIV epidemic.

Mortality among a group of known drug users shows small numbers of deaths from AIDS so far but increasing deaths from overdose, especially in young women. Steadily rising numbers of drug injectors are observed. The need for a distinctly different educational approach in areas of very high seroprevalence is discussed and the requirement for close co-operation between prescribing sources identified.

After the epidemic: follow up study of HIV seroprevalence and changing patterns of drug use.

OBJECTIVE: To follow up known intravenous drug users to determine current health state and drug use, compare characteristics with those of recent drug users, and examine HIV exposure and serostate. DESIGN: Subjects were identified from conventional general practice records and recruited from 1980 to the end of 1985; they were followed up during 1987 and 1988 and compared with drug users identified in the same way but recruited after 1985. SETTING: General practice and community in north west Edinburgh. Follow up conducted throughout the United Kingdom. SUBJECTS: Subjects known to have injected illegal drugs before 1986 (n = 203) and since that time. MAIN OUTCOME MEASURES: Mortality from and prevalence of HIV seropositivity and various parameters indicative of abstinence. RESULTS: Of the 203 subjects in the follow up group, 189 (93%) were traced; 16 (8%) had died and the remaining 173 (85%) were interviewed. In all, 146 (72% of the follow up cohort) had been tested for HIV antibodies, 94 (64%) having positive and 52 (36%) negative results; 57 (28%) had not been tested. Of the 65 subjects in the recently recruited group, 51 (79%) had been tested for HIV, 15 (29%) having positive results. A further 21 (43%) were currently negative for HIV antibody but still at risk. Thirty three (19%) of those followed up were confirmed abstinent, although more (about half) showed evidence of diminished drug injecting. Age correlated strongly with abstinence (p less than 0.001). One third of the group currently used cannabis, buprenorphine, dihydrocodeine, or diazepam. When the two groups were analysed together there was a strong association between the date of starting injecting and HIV seropositivity (chi 3 = 23.81, df = 2, p less than 0.001), with a peak around 1980-3. CONCLUSIONS: Although only a fifth of the followed up group were convincingly abstinent, a much larger group showed evidence of prolonged periods of remission. Overall, much use of oral drugs was confirmed and worrying trends towards taking buprenorphine and benzodiazepines were evident. The peak incidence of starting drug use and the comparatively low seroprevalence of HIV in the newer drug users probably explain the anomalous high seroprevalence in Edinburgh drug users during 1980-5. The epidemic of HIV during the first half of the 1980s in the group suggests that the virus was probably being transmitted because of a pattern of behaviour. Changing patterns of HIV transmission suggest a need to concentrate on heterosexual transmission as the main problem in the future.