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Biomedical subjects

L Atkins

Publications and source records attributed to L Atkins.

At least 19 recordsLinked to original sources

Health-related locus of control: does it change in motor neurone disease (MND)?

OBJECTIVES: Previous studies have attempted to describe locus of control beliefs in people with MND. This exploratory, longitudinal study set out to examine some of the possible correlations of health-related locus of control beliefs and the stability of these beliefs. METHOD: 32 people with Motor Neurone Disease completed the Multi-dimensional Health Locus of Control (MHLC) scale, initially on average 10.3 months after diagnosis, and again on average 16.4 months after diagnosis. Physical symptoms were assessed at both times. RESULTS: Initially there were no correlations between MHLC beliefs or disease duration and physical symptomatology, although longer disease duration was associated with greater beliefs in the role of powerful others in health control. At the second assessment, belief in the role of powerful others controlling health had increased, with this increase relating significantly to a worsening in physical symptoms. At this second assessment, neither duration of symptoms nor time since diagnosis correlated with MHLC beliefs. CONCLUSIONS: Whilst health locus of control beliefs do appear to change in MND, current findings suggest that this does not occur simply as a function of the passage of time. How symptoms change seems to be of particular importance when considering health locus of control beliefs in people with MND. Suggestions are made concerning other factors that might usefully be examined in future studies of this type.

Aged↗

Predictors of institutionalisation in people with dementia.

OBJECTIVE: To identify what patient and carer characteristics influence transition into residential care for people with dementia. METHOD: Longitudinal study of a cohort of people with dementia and their carers in contact with old age psychiatric services in south London. RESULTS: 100 people with dementia and their main family carer were recruited. At six month follow up 22 were in residential care, 63 in the community, 8 had died, and for 7 there were missing data. Between six and 12 months, 7 of the 63 in the community went into residential care, 4 died, and 12 were lost to follow up. The most striking finding is the 20-fold protective effect of having a co-resident carer (odds ratio 0.05, 95% confidence intervals 0.01 to 0.42, p=0.006). Higher ratings of behavioural problems in the person with dementia were also statistically significantly associated with transition into residential care as was the psychological domain of quality of life of the carer. CONCLUSION: These findings powerfully illustrate the pivotal role carried out by carers of people with dementia; interventions directly targeted at helping them to maintain this role would be supported by these data. These data also suggest that strategies directed at improving carer quality of life and at the resolution of behavioural disorder in the person with dementia may also have particular value.

Adult↗

Correlates of Quality of Life in people with motor neuron disease (MND).

OBJECTIVES: Previous work has not found correlations between standardized questionnaire measures of quality of life (QoL) and physical strength/functional ability in people with motor neuron disease (MND). Little is known about the relationship between ratings on an abbreviated self-generated measure of QoL, the Schedule for Evaluation of Individual Quality of Life-Direct Weighting (SEIQoL-DW), and measures of functional status such as the Sickness Impact Profile (SIP), although the former has been rated by people with MND as providing a more valid measure of their own QoL than the latter. The aim of this study was to examine whether self-generated ratings of QoL correlated with measures of physical impairment and self-reported functional status, psychological wellbeing and self-reported cognitive functioning, and with factors such as social support, which elsewhere has been reported to be a determinant of QoL in MND. DESIGN: The present cross-sectional study investigated between SEIQoL-DW ratings and SIP and the relationship ALS Severity Scale (ALSSS) scores, as well as with self-reported anxiety, depression, social support and everyday cognitive functioning in 31 people with MND. RESULTS: Overall QoL ratings on the SEIQoL-DW failed to correlate with any of the ALSSS or SIP subscale scores. This was despite the fact that health was nominated as an important QoL-related category by 64.5% of the sample. QoL scores were, however, found to correlate positively with the existence of confiding and emotional support; they also correlated negatively with the presence of self-rated everyday cognitive difficulties but not with affective state. CONCLUSIONS: Current findings support recent observations that individuals' ratings of their QoL cannot simply be equated with their physical impairment and functional limitations, and that support systems may be important. Cognitive functioning, known to be impaired in some people with MND, should also be considered when evaluating QoL.

Cognition Disorders↗

Pituitary tumorigenesis and hPit-1 cells.

Despite decades of clinical data verifying the success of therapeutic approaches to human pituitary tumors, a significant number of tumors progress and can be life-threatening. The development of better therapeutic strategies for pituitary tumors is complicated by the relative scarcity of human pituitary material for basic experimentation. Human pituitary tissue was used to derive cell cultures, and a cell line, hPIT-1. Molecular and functional analyses were used to further characterize the cells as human pituitary explants in vitro. Functional analyses of the cell cultures indicated that the cells were tumorigenic and of human folliculostellate origin. hPit-1 cells revealed numerous abnormalities of ploidy. Molecular analyses indicated the absence of expression of the following pituitary hormones or hormone subunits by this culture: growth hormone, prolactin, ACTH, FSHbeta, LHbeta, THbeta, and p-glycoprotein. By contrast, the cells expressed uniformly high levels of human follistatin mRNA. Finally, the cells are moderately tumorigenic in immune-deficient mice. Although the precise molecular genetic mechanisms for tumorigenesis in the established cell culture are unknown, the cells serve as a future resource in the study of pituitary tumor initiation, progression, and response to therapy.

Adult↗

Amplification of AML1 in childhood acute lymphoblastic leukemias.

Amplification of AML1 has been confirmed by fluorescence in situ hybridization analysis in two cases of childhood acute lymphoblastic leukemia. It remains to be elucidated whether this amplification results in up-regulation of the normal AML1 gene product or a potentially mutant AML1 transcript.

Child↗

Characterization of a xenograft model of human ovarian carcinoma which produces intraperitoneal carcinomatosis and metastases in mice.

A new xenograft model for human epithelial ovarian carcinoma, with extensive intraperitoneal (i.p.) carcinomatosis as the predominant disease manifestation, is described. Cells from the established NIH:OVCAR-5 cell line were injected i.p. into 6- to 8-week-old Swiss nude mice. Comparative analyses between cells cultured in vitro and tumor cells derived ex vivo were performed to assess histologic features, immunohistochemical cell markers, hormonal receptor expression, adhesion to extracellular matrix molecules and chromosomal constitution. Macroscopically, the extent of tumor development appeared to be site-dependent and tumor cell survival was dose-dependent. Advanced disease was characterized by extensive solid tumor burden and ascites with parenchymal invasion, lymphatic metastases and vascular dissemination. Individual tumor nodules exhibited developing neovasculature characterized by the absence of mature basement membrane. Despite some histologic loss of cellular differentiation in advanced disease, antigenic expression was preserved, distinguishing these cells as epithelial in origin. Karyotyping of tumor cells demonstrated multiple numeric and structural chromosomal abnormalities. Serum and ascites CA 125 levels were consistently elevated only in tumor-bearing mice. This new murine model closely resembles the aggressive disease process of human epithelial ovarian carcinoma, in which the efficacy of i.p. and systemic therapeutic modalities can be investigated.

Animals↗

Health reform: what to expect from the coming debate. Interview by Jeannie Mankelker, Dan Wise, and Steven Findlay.

Health care reform is in limbo as 1994 draws to a close. Last month's Republican sweep puts the issue in a starkly new political environment. The new Congressional leadership said last month it will put forth a reform plan in 1995. Also, the Clinton administration is working on a scaled-back proposal. To get an idea of what might happen next year, we invited 20 informed persons to give us their opinions and to tell us what action they'd prefer. Because of B&H's production schedule, the interviews took place before the election. We don't think that diminishes their insights and analyses.

Forecasting↗

Trisomy 5 and trisomy 7 are nonrandom aberrations in pigmented villonodular synovitis: confirmation of trisomy 7 in uncultured cells.

Pigmented villonodular synovitis (PVNS) is a proliferative lesion of disputed genesis. Recently, we reported trisomy 7 in short-term cultures of 1 PVNS. In the present report, we describe another specimen of PVNS in which 9 of 26 (35 percent) metaphase cells demonstrated trisomy 7 when analyzed after 3-15 days of tissue culture. In situ hybridization analysis, with a biotinylated probe to chromosome 7 alpha-satellite DNA, revealed trisomy 7 in 53 of 200 uncultured cells from this PVNS sample. Our findings indicate that trisomy 7 is a nonrandom aberration that arises in vivo in PVNS.

Chromosomes, Human, Pair 5↗

Changes in AMP deaminase activities in the hearts of diabetic rats.

AMP deaminase from normal and diabetic rat hearts was separated on cellulose phosphate and quantitated by HPLC. From soluble fractions three different AMP deaminase activities, according to KCl elution from cellulose phosphate and percent of total activity were: 170 mM (85%), 250 mM (8%) and 330 mM (7%) KCl. The AMP deaminase activity which eluted with 170 mM KCl was resolved to two distinct peaks by HPLC anionic exchange. After 4 weeks of diabetes the heart enzyme profile change to: 170 mM (10%), 250 mM (75%) and 330 mM (15%). Once purified the four activities were kinetically distinct: 170 mM KCl cytosolic, AMP Km = 1.78, stimulated by ATP, GTP, NADP and strongly inhibited by NAD; 170 mM KCl mitochondria AMP Km = 17.9, stimulated by ATP, ADP; 250 mM KCl isozyme, AMP Km = 0.66, stimulated by ADP; and 330 mM KCl isozyme, AMP Km = 0.97, inhibited by ATP, NAD(P).

AMP Deaminase↗

Loss of the Y chromosome in meningiomas. A molecular genetic approach.

Loss of the Y chromosome in meningiomas from 17 male patients was examined by cytogenetic analysis and by Southern blot hybridization with a series of Y-specific DNA probes. Cytogenetic analysis revealed loss of the Y chromosome in seven of 17 (41%) of the tumors whereas Southern blot hybridization showed loss of Y-associated sequences in only three of 17 (18%). Although the incidence of Y-chromosome loss was less by Southern blot hybridization than by cytogenetic analysis, the finding that loss of Y is present in the original uncultured tumor specimen suggests that a gene or genes on the Y chromosome may play a role in growth control of meningioma cells, and loss of this gene may be associated with tumor progression. The difference in the incidence of Y loss between the two methods indicates that both methods should be used when examining chromosome losses.

Adult↗

[Polymorphism of restriction fragment length in the detection of the precise status of monosomy 21 in a deformed retarded girl].

The authors used genomic single copy DNA fragments cloned from chromosome 21 to study cytogenetic abnormalities in patients not easily defined by conventional cytogenetic means. Ten restriction fragment length polymorphisms (RLFP) detected by 8 independent probes were used to detect homologous sequences from chromosome 21 in genomic digests of DNA from one patient and her parents. The proband is a 3 1/2-year-old girl who was referred to us at 1 month of age because of hypertonia, hirsutism, flattened nasal bridge, antimongoloid slant of palpebral fissures, high arched palate and bilateral hip dysplasia. The karyotype of the proband was: 46, XX, -3, -21, + ? del (3) (3 pter----3q1:) +? (3qter----3q1:: 21q21----21 pter). GTG banding and the karyotype of her parents were normal (in peripheral blood and skin fibroblasts). She was re-examined by us every three months, because she showed physical and psychomotor retardation. We traced the inheritance of RFLPs from her parents, and familial molecular studies showed in contrast to the cytogenetic analysis that the patient is disomic for all regions of 21q tested by our collection of probes. The use of molecular technology has resulted in a more precise definition of 21 chromosome abnormalities and especially the "complete" monosomy 21 which is extremely rare in live born infants.

Abnormalities, Multiple↗

Familial premature ovarian failure due to an interstitial deletion of the long arm of the X chromosome.

We describe a family in which four women had menstrual irregularities and a partial deletion of the long arm of the X chromosome (Xq). Three of the four women had premature ovarian failure (at the ages of 24 to 37 years). Chromosome-banding studies initially suggested that a terminal portion of Xq was deleted. However, DNA-hybridization studies showed that an interstitial portion of Xq was deleted and that the affected women had a 46,XX,del(X)(pter-q21.3::q27-qter) karyotype. These findings help clarify the role of Xq in ovarian function and indicate that the accurate description of such abnormalities requires a combination of cytogenetic and DNA-hybridization analysis.

Adult↗

Molecular genetic approach to human meningioma: loss of genes on chromosome 22.

A molecular genetic approach employing polymorphic DNA markers has been used to investigate the role of chromosomal aberrations in meningioma, one of the most common tumors of the human nervous system. Comparison of the alleles detected by DNA markers in tumor DNA versus DNA from normal tissue revealed chromosomal alterations present in primary surgical specimens. In agreement with cytogenetic studies of cultured meningiomas, the most frequent alteration detected was loss of heterozygosity on chromosome 22. Forty of 51 patients were constitutionally heterozygous for at least one chromosome 22 DNA marker. Seventeen of the 40 constitutionally heterozygotic patients (43%) displayed hemizygosity for the corresponding marker in their meningioma tumor tissues. Loss of heterozygosity was also detected at a significantly lower frequency for markers on several other autosomes. In view of the striking association between acoustic neuroma and meningioma in bilateral acoustic neurofibromatosis and the discovery that acoustic neuromas display specific loss of genes on chromosome 22, we propose that a common mechanism involving chromosome 22 is operative in the development of both tumor types. Fine-structure mapping to reveal partial deletions in meningiomas may provide the means to clone and characterize a gene (or genes) of importance for tumorigenesis in this and possibly other clinically associated tumors of the human nervous system.

Brain Neoplasms↗

Interstitial deletion and ring chromosome derived from 16q.

An interstitial deletion of 16q was identified in an infant with failure to thrive, dysmorphic facies, and congenital heart defects. The mother of this infant had a similar deletion of 16q with ring formation of a fragment presumed to be derived from the deleted portion of 16q. We discuss these cases and compare them to other reports of 16q deletions.

Abnormalities, Multiple↗