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Biomedical subjects

M Davies

Publications and source records attributed to M Davies.

At least 217 records · Page 12Linked to original sources

Psychometrics of neurological soft signs.

OBJECTIVE: To examine the psychometrics of neurological soft signs in young children. METHOD: In a sample of 42 children from the community, two examiners simultaneously rated soft signs using a standardized examination. A subsample (n = 33) was reexamined twice over the next week to estimate test-retest reliability. RESULTS: Total score exhibited acceptable internal consistency as well as interrater and test-retest reliability. Psychometrics for individual items appeared less satisfactory than for the total score. DISCUSSION: Although examiners can reliably rate a variety of soft signs, more research examining test-retest reliability is needed. A reliable examination might be useful in future efforts to document the neuropsychiatric correlates of soft signs.

Child↗

The NIMH Methods for the Epidemiology of Child and Adolescent Mental Disorders (MECA) Study: background and methodology.

OBJECTIVE: A collaborative study was conducted to develop methods for surveys of mental disorder and service utilization in unscreened population-based samples of children and adolescents. METHOD: Probability household samples of youths 9 through 17 years of age were selected at four sites and interviews were conducted with a total of 1,285 pairs of youths and their adult caretakers in their homes. Lay interviewers administered a computer-assisted version of the NIMH Diagnostic Interview Schedule for Children Version 2.3 and structured interviews to assess demographic variables, functional impairment, risk factors, service utilization, and barriers to service utilization. RESULTS: More than 7,500 households were enumerated at four sites, with enumeration response rates above 99%. Across sites, 84% of eligible youth-caretaker pairs were interviewed for about 2 hours each. Ninety-five percent of both youths and caretakers found the interview to be acceptable enough to recommend to a friend. CONCLUSIONS: These findings indicate that large-scale epidemiological surveys of mental disorders and mental health service use involving lengthy interviews in the homes of unscreened population-based samples of youths and their adult caretakers are acceptable to the community and can achieve good response rates. The other reports in this Special Section address the reliability and validity of the various survey instruments and other key findings.

Adolescent↗

The NIMH Diagnostic Interview Schedule for Children Version 2.3 (DISC-2.3): description, acceptability, prevalence rates, and performance in the MECA Study. Methods for the Epidemiology of Child and Adolescent Mental Disorders Study.

OBJECTIVE: To describe the NIMH Diagnostic Interview Schedule for Children (DISC) Version 2.3 and to provide data on its performance characteristics in the Methods for the Epidemiology of Child and Adolescent Mental Disorders (MECA) Study. METHOD: Data were collected on the DISC-2.3 at four sites on 1,285 randomly selected children, aged 9 through 17 years, and their parents. Two hundred forty-seven of these child-parent pairs were reassessed on the DISC-2.3 by a clinician interviewer, 1 to 3 weeks later. RESULTS: Administration time was approximately 1 hour and the interview was acceptable to more than 90% of subjects. The reliability of questions to parents assessing impairment and age of onset was generally good to acceptable for most diagnoses but was less satisfactory for the child interview. Using information from parent and child, the prevalence for any diagnosis ranged from 50.6 if no impairment criteria were required to 5.4 if a Global Assessment Scale score of 50 or less was necessary. The prevalence of anxiety disorders and enuresis was markedly reduced by requiring attributable impairment. CONCLUSIONS: The DISC-2 is a reliable and economical tool for assessing child psychopathology. Reliability of the DISC-P-2.3 is superior to that of the child DISC for most diagnoses but is least good for anxiety disorders. The 2.3 version of the instrument provides a significant improvement over earlier versions.

Adolescent↗

A longitudinal study of cognitive abilities and educational attainment in Williams syndrome.

The paper reports on changes in IQ scores and in reading, spelling and arithmetic skills over time in 23 young adults with Williams syndrome. They were first assessed in their early to mid-teens and followed up 8 to 9 years later, at an average age of 21 years 9 months. Cognitive assessments indicated increases in Full Scale, Verbal and Performance IQ scores. These increases allow us to conclude that in the case of Williams syndrome (unlike some other conditions) there does not appear to be a decline in the rate of cognitive development over time. Comparisons of Reading, Spelling and Arithmetic scores attained at first and second testing periods revealed only modest increases in reading accuracy and spelling scores, a slight decline in reading comprehension scores, and little change in arithmetic test scores. Differences in the tests used at the two assessment periods do not allow for definitive conclusions to be drawn, but the findings suggest that individuals with Williams syndrome make little progress in their educational skills beyond their early teenage years.

Adolescent↗

Upregulation of basement membrane-degrading metalloproteinase secretion after balloon injury of pig carotid arteries.

Basement membrane-degrading metalloproteinases (gelatinases) appear necessary for vascular smooth muscle cell migration and proliferation in culture and for intimal migration of cells after balloon injury to the rat carotid artery. We investigated in the present study the secretion of gelatinases from pig carotid artery tissue after balloon injury. Segments of injured artery and segments proximal and distal to the area of injury were removed 3, 7, and 21 days after balloon dilatation. Medial explants from these segments were then cultured for 3 days, and the serum-free conditioned media were subjected to gelatin zymography. Production of 72- and 95-kD gelatinases was quantified by densitometry. Balloon-injured segments secreted significantly more 72- and 95-kD gelatinase than did paired distal segments at all time points. Release of both gelatinase activities was increased at 3 and 7 days relative to segments from uninjured arteries but declined again by 21 days after balloon injury. Similar results were found for gelatinase levels in extracts of arterial tissue. Consistent with the protein secretion data, in situ hybridization demonstrated that the mRNAs for both gelatinases were upregulated after balloon injury. Expression was prominent in medial smooth muscle cells, particularly around foci of necrosis, and in neointimal cells 3 and 7 days after balloon injury; 72-kD gelatinase mRNA persisted after 21 days and was prominent in regrown endothelial cells. The upregulation of gelatinase activity paralleled the time course of smooth muscle cell migration and proliferation in this model. We conclude that increased gelatinase production occurs in response to balloon injury and may play a role in permitting migration and proliferation of vascular smooth muscle cells.

Animals↗

Novel and sensitive detection systems for the vitamin D receptor--in situ-reverse transcriptase-polymerase chain reaction and immunogold cytochemistry.

The receptor for the active metabolite of vitamin D, 1,25(OH)(2)D(3), known as the vitamin D receptor (VDR), belongs to the steroid hormone nuclear receptor superfamily. We have developed novel methods for detection of VDR mRNA and protein within a human promyelomonocytic cell line, HL-60. Using the newly developed technique of in situ-reverse transcriptase-polymerase chain reaction (IS-RT-PCR), low levels of VDR mRNA could be amplified and demonstrated unequivocally within these cells, and also within a human kidney proximal tubule cell line, CL-8. Use of a novel immunogold cytochemical technique has allowed clear and sensitive detection of VDR protein expression within the HL-60 cells. Further development of IS-RT-PCR has allowed us to apply this technique to tissue sections. We have shown clear amplification of VDR transcripts within sections of formalin-fixed paraffin-embedded human kidney and liver. These techniques will be useful to localise specifically the VDR within cell types that contain low levels of mRNA and protein, and will permit further investigation of the role played by 1,25(OH)(2)D(3) in cellular regulatory mechanisms.

Base Sequence↗

Water fluoridation in Australia.

This paper reviews the rationale, context and support for water fluoridation in Australia, and examines current Australian evidence concerning the caries-preventive effects of fluoridation and trends in dental fluorosis. Nearly two thirds of the Australian population resides in an area with adjusted levels of fluoride in the water supply. However, public knowledge about fluoridation is poor and opinion polls demonstrate declining support for fluoridation. In the press and scientific literature there has been questioning of fluoridation, although the most recent Australian review reasserted its safety and effectiveness. Results from Australian oral epidemiological studies consistently support the accumulated evidence on the effectiveness of water fluoridation. This includes recent evidence that lifetime exposure to fluoridation is associated with average reductions of 2.0 dmfs and between 0.12 and 0.30 DMFS per child compared with non-exposed children. Water fluoridation has been found to reduce socio-economic inequalities in caries, reducing the differential between high and low socio-economic status groups by approximately 1.0 dmfs and 0.2 DMFS per child. The prevalence of dental fluorosis may have increased, prompting renewed consideration of overall exposure to fluorides. Action is currently being taken to reduce the exposure to discretionary fluoride among pre-school children as part of a targeted approach to adjusting the benefit-risk relationship of exposure to fluorides for that age group. Community water fluoridation continues to be the most effective and socially equitable measure for caries prevention among all ages by achieving community-wide exposure to the caries preventive effects of fluoride.

Adult↗

Perioperative nursing--a course for the future.

Australia is home to a number of endangered species--the koala perhaps being the most well known. I will discuss another familiar species which is nonetheless in danger of extinction--the perioperative registered nurse. My paper will propose a strategy to increase their numbers within their normal habitat of the operating suite.

Australia↗

Health-related quality of life in primary care patients with mental disorders. Results from the PRIME-MD 1000 Study.

OBJECTIVE: To determine if different mental disorders commonly seen in primary care are uniquely associated with distinctive patterns of impairment in the components of health-related quality of life (HRQL) and how this compares with the impairment seen in common medical disorders. DESIGN: Survey. SETTING: Four primary care clinics. SUBJECTS: A total of 1000 adult patients (369 selected by convenience and 631 selected by site-specific methods to avoid sampling bias) assessed by 31 primary care physicians using PRIME-MD (Primary Care Evaluation of Mental Disorders) to make diagnoses of mood, anxiety, alcohol, somatoform, and eating disorders. MAIN OUTCOME MEASURES: The six scales of the Short-Form General Health Survey and self-reported disability days, adjusting for demographic variables as well as psychiatric and medical comorbidity. RESULTS: Mood, anxiety, somatoform, and eating disorders were associated with substantial impairment in HRQL. Impairment was also present in patients who only had subthreshold mental disorder diagnoses, such as minor depression and anxiety disorder not otherwise specified. Mental disorders, particularly mood disorders, accounted for considerably more of the impairment on all domains of HRQL than did common medical disorders. Finally, we found marked differences in the pattern of impairment among different groups of mental disorders just as others have reported unique patterns associated with different medical disorders. Whereas mood disorders had a pervasive effect on all domains of HRQL, anxiety, somatoform, and eating disorders affected only selected domains. CONCLUSIONS: Mental disorders commonly seen in primary care are not only associated with more impairment in HRQL than common medical disorders, but also have distinct patterns of impairment. Primary care directed at improving HRQL needs to focus on the recognition and treatment of common mental disorders. Outcomes studies of mental disorders in both primary care and psychiatric settings should include multidimensional measures of HRQL.

Adult↗

Effects of pulsed beta-stimulant therapy on beta-adrenoceptors and chronotropic responsiveness in chronic heart failure.

In animals, intermittent sympathomimetic stimulation with dobutamine produces benefits analogous to those of physical conditioning. Longer intermittent or continuous beta-stimulant therapies have not, however, been successful in managing patients with chronic heart failure. We have investigated the role of beta-receptor stimulants in patients with severe chronic heart failure by changing the method of administration to intermittent, very short-duration pulsed intrope therapy (PIT). We studied 10 patients (mean age 64 [SE 2] years) with stable moderate to severe chronic heart failure (ejection fraction 23 [3]%) who received PIT, and 10 control patients matched for age and severity. We infused sufficient dobutamine to raise heart rate to 70-80% maximum for 30 min per day, 4 days per week for 3 weeks. PIT increased exercise tolerance (from 10.4 [1.2] min at baseline to 13.0 [1.5] min at 3 weeks; p < 0.001, 95% CI for difference 1.6 to 3.9) and lowered peripheral vascular resistance (19.8 [3.1] to 17.7 [2.4] mm Hg.min.L-1; p < 0.05, -4.1 to -0.1). PIT produced significant increases in lymphocyte beta-receptor density (502 [110] to 1200 [219] per cell, p < 0.02, 258 to 1138) and chronotropic responsiveness to exercise (change in heart rest to peak exercise 51.0 [3.2] to 57.5 [3.9] beats per min; p < 0.01, 2.9-10.1). Plasma noradrenaline concentrations (2.39 [0.28] to 1.65 [0.19] nmol/L, p < 0.05) were reduced. The patients' symptoms were also improved. By contrast, no change in autonomic function or exercise capacity was seen in the control group. Short-duration PIT induces pharmacological conditioning with improved symptoms, autonomic balance, exercise tolerance, beta-receptor up-regulation, and enhanced chronotropic responsiveness in chronic heart failure.

Aged↗

Modulation by copper of p53 conformation and sequence-specific DNA binding: role for Cu(II)/Cu(I) redox mechanism.

The tumor suppressor protein p53 is a metal-binding transcription factor whose conformation and function are altered by mutation in cancers. Using murine p53 translated in vitro, we report here that concentrations of copper within the physiological range (< 30 microM) alter the conformation of wild-type p53 and inhibit sequence-specific DNA-binding. Direct binding of copper to p53 in the form of Cu(I) was demonstrated by Electron Spin Resonance using a purified recombinant protein containing residues 1-343 of murine wild-type p53 fused to E. coli maltose binding protein. Moreover, protection against the effect of Cu(II) sulfate was achieved by the Cu(I)-specific chelator bathocuproinedisulfonic acid but not by scavengers of reactive oxygen species, suggesting that alteration of p53 by copper depends upon a Cu(II)/Cu(I) redox mechanism, but does not require the production of reactive oxygen species. Thus copper at physiological concentrations can interact with wild-type p53 and affect its DNA-binding capacity.

Animals↗

Test-retest reliability of the Diagnostic Interview Schedule for Children (DISC 2.1). Parent, child, and combined algorithms.

BACKGROUND: Previous research has not compared the psychometric properties of diagnostic interviews of community samples and clinically referred subjects within a single study. As part of a multisite cooperative agreement study funded by the National Institute of Mental Health, 97 families with clinically referred children and 278 families identified through community sampling procedures participated in a test-retest study of version 2.1 of the Diagnostic Interview Schedule for Children (DISC 2.1). METHODS: The DISC was separately administered to children and parents, and diagnoses were derived from computer algorithms keyed to DSM-III-R criteria. Three sets of diagnoses were obtained, based on parent information only (DISC-P), child information only (DISC-C), and information from either or both (DISC-PC). RESULTS: Test-retest reliabilities of the DISC-PC ranged from moderate to substantial for diagnoses in the clinical sample. Test-retest kappa coefficients were higher for the clinical sample than for the community sample. The DISC-PC algorithm generally had higher reliabilities than the algorithms that relied on single informants. Unreliability was primarily due to diagnostic attenuation at time 2. Attenuation was greatest among child informants and less severe cases and in the community sample. CONCLUSIONS: Test-retest reliability findings were consistent with or superior to those reported in previous studies. Results support the usefulness of the DISC in further clinical and epidemiologic research; however, closely spaced or repeated DISC interviews may result in significant diagnostic attenuation on retest. Further studies of the test-retest attenuation phenomena are needed, including careful examination of the child, family, and illness characteristics of diagnostic stability.

Adolescent↗

Extracellular matrix proteins modulate cytochrome P450 2D6 expression in human hepatocytes.

The role of extracellular matrix proteins on the expression of human liver-specific genes has been investigated. Cytochrome P450 2D6 and albumin are two liver-specific genes which are constitutively expressed in hepatocytes. Primary human hepatocytes were cultured on different extracellular matrix proteins, namely collagen, fibronectin, a combination of collagen/fibronectin and EHS-laminin rich gel, and under different culture conditions. After 48 h in culture, primary human hepatocytes showed a peak in DNA-synthesis associated with a downregulation of liver-specific expression of albumin and P450 2D6, indicating the dedifferentiation of the hepatocytes. Differentiation and expression of liver-specific genes started to increase subsequently. Redifferentiation as determined by albumin and P450 2D6 levels was more pronounced if hepatocytes were seeded on fibronectin, compared to cells seeded on EHS-laminin rich gel, collagen or a combination of collagen and fibronectin.

Blotting, Northern↗