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Biomedical subjects

A Richardson

Publications and source records attributed to A Richardson.

At least 109 records · Page 6Linked to original sources

A proportional analysis of some facial height and depth variables in 10 to 16 year old children.

A method for analysing the horizontal and vertical proportions of the face is described, based on natural head orientation (NHO). It demonstrates how individual deviations from the mean proportions can be quantified both horizontally and vertically. Correlation between facial depth to height (index 1) and the mandibular plane angle was determined and found to be fairly strong and highly significant (r = 0.5, P < 0.001). Facial depth to height and lower facial height to total facial height (index 2) relationships were found to be strongly correlated at each age between 10 and 16 years, with only small mean differences. For this reason the norm values presented for 12-year-old children for indices 1 and 2 should be applicable to orthodontic patients within this age range. The relationship between mandible and maxilla (index 3) increases continually between 10 and 16 years in boys, and between 10 and 14 years in girls, about 0.3 units a year. It can provide supplementary information for individual case analysis. For boys the increase was 2.2 units per year between 14 and 16 years of age.

Adolescent↗

Diet restriction increases apoptosis in the gut of aging rats.

Previous studies have shown that epithelial cell production rates are increased throughout the gastrointestinal tract in aging rats. We tested the hypothesis that alteration in cell death (apoptosis) might be involved. Fischer 344 rats aged 4-5 months and 24-25 months fed ad libitum (AL) or calorie restricted (CR) to 60% of the AL intake were studied. Epithelial cell apoptosis was determined by a terminal deoxyuridine nucleotidyl nick end labeling (TUNEL) technique validated in our laboratory, and the expression of four members of the Bcl-2 family was evaluated by Western blotting in the small intestine and colon. The apoptotic index was low in young and aging AL and young CR rats. However, CR in aging rats was associated with a significantly higher apoptotic index in the jejunum and colon. The expression of the Bcl-2 family of genes was unchanged. Enhanced apoptosis in CR may protect the gastrointestinal tract from accumulation of DNA-altered cells during the aging process.

Aging↗

Genome-wide search for asthma susceptibility loci in a founder population. The Collaborative Study on the Genetics of Asthma.

Founder populations offer many advantages for mapping genetic traits, particularly complex traits that are likely to be genetically heterogeneous. To identify genes that influence asthma and asthma-associated phenotypes, we conducted a genome-wide screen in the Hutterites, a religious isolate of European ancestry. A primary sample of 361 individuals and a replication sample of 292 individuals were evaluated for asthma phenotypes according to a standardized protocol. A genome-wide screen has been completed using 292 autosomal and three X-Y pseudoautosomal markers. Using the semi-parametric likelihood ratio chi2 test and the transmission-disequilibrium test, we identified 12 markers in 10 regions that showed possible linkage to asthma or an associated phenotype (likelihood ratio P < 0.01). Markers in four regions (5q23-31, 12q15-24.1, 19q13 and 21q21) showed possible linkage in both the primary and replication samples and have also shown linkage to asthma phenotypes in other samples; two adjacent markers in one additional region (3p24.2-22) showing possible linkage is reported for the first time in the Hutterites. The results suggest that even in founder populations with a relatively small number of independent genomes, susceptibility alleles at many loci may influence asthma phenotypes and that these susceptibility alleles are likely to be common polymorphisms in the population.

Adolescent↗

Fatigue in patients receiving chemotherapy: patterns of change.

Fatigue is reported to be a significant and distressing problem for people receiving chemotherapy, but the phenomenon is poorly understood and little is known about the factors influencing it. Nurses need to understand the dimensions of fatigue in order to provide effective help for individuals with cancer who experience it. This article describes a study that employed a daily diary with the aim of prospectively charting the onset, pattern, duration, intensity, and distress associated with fatigue in 109 patients receiving chemotherapy. The diary comprised four visual analogue scales measuring selected dimensions of fatigue: extent of fatigue, distress caused by fatigue, the influence of fatigue on the ability to engage in social activities, and the impact of fatigue on work-related activities. The patients' diaries produced detailed time series of data that captured the dynamics of their fatigue. Analyses of these data revealed the patterns of fatigue after the administration of chemotherapy, which appear strongly related to both the timing of treatment and the manner in which cytotoxic agents are administered. Furthermore, Kruskal-Wallis tests performed to compare fatigue among subgroups of patients revealed that it is statistically associated with particular types of cancer, specific chemotherapy regimens, and certain methods of drug administration. Fatigue varied throughout the day, more frequently occurring in the afternoon and early evening. These insights, gained during this study about the likely pattern of fatigue in the period after the administration of chemotherapy, and the potential benefits of maintaining a fatigue diary could be utilized by nurses engaged in the care of chemotherapy patients.

Activities of Daily Living↗

Encapsidation studies of poliovirus subgenomic replicons.

The inclusion of a foreign marker gene, chloramphenicol acetyltransferase (CAT) gene, into the poliovirus genome allows its replication and encapsidation to be easily monitored using a simple enzyme assay. Such poliovirus replicons require the presence of helper virus for their successful propagation and thus are similar to defective interfering (DI) viruses. In genomes containing the CAT gene, the majority of the P1 virus capsid region of the poliovirus genome could be removed without destroying viability. The smallest replicon was significantly smaller than any naturally occurring DI particle so far reported, yet it retained the ability to replicate and be encapsidated by structural proteins provided by helper virus in trans. The efficiency with which the replicons were encapsidated was investigated using a direct immunostaining technique that allows individual cells infected with either a replicon or helper virus to be quantified. These results were compared to the frequencies of trans-encapsidation of polioviruses and coxsackievirus B4 using a two-stage neutralization assay. Poliovirus types 1, 2 and 3 but not coxsackievirus B4, coxsackievirus A21 or rhinovirus 14 provided efficient trans-encapsidation of poliovirus type 3 or type 3-derived replicons. These results suggest that a specific encapsidation process operates and that it does not involve RNA sequences within the region of the genome encoding the capsid proteins.

Animals↗

Effect on attendance at breast cancer screening of adding a self administered questionnaire to the usual invitation to breast screening in southern England.

STUDY OBJECTIVE: The primary aim of the research described in this paper was to ascertain whether inclusion of a self administered questionnaire with the usual invitation to routine breast screening affected screening uptake. Secondary aims included establishing appropriate questionnaire distribution and collection methods within the framework of the National Health Service Breast Screening Programme and optimisation of questionnaire design. DESIGN: Randomised study. SETTING: Oxfordshire and West of London Breast Screening Units. PARTICIPANTS/METHODS: 6400 women invited for routine screening mammography were individually randomised to receive either the usual breast screening invitation alone, or to receive the usual invitation accompanied by a self administered questionnaire, to be returned at the time of screening. Participants were then followed up and attendance rates at screening were compared between groups. MAIN RESULTS: Screening attendance rates were similar in women who did and did not receive a questionnaire (71% in each group). Of those who were sent a questionnaire and attended for screening, 77% returned a completed questionnaire. Screening uptake was not affected by the way in which the questionnaire was returned or by whether or not personal details and signed permission for follow up were requested. CONCLUSIONS: The inclusion of a self administered questionnaire accompanying the invitation to breast screening did not adversely affect screening uptake. A high proportion of women completed the questionnaire.

Breast Neoplasms↗

A double blind, randomised, parallel group study to investigate the dose equivalence of Dysport and Botox in the treatment of cervical dystonia.

OBJECTIVE: This study was designed to establish whether a ratio of three units of Dysport is equivalent to one unit of Botox for the treatment of cervical dystonia. METHODS: Patients with predominantly rotational cervical dystonia, and a minimum of four previous Botox treatments, were randomised to receive either the clinically indicated dose of Botox or three times that dose in Dysport units. Study botulinum toxin was administered in a double blind fashion, to one or more clinically indicated muscles, at one or more sites per muscle. Patients returned for assessment two, four, eight, and 12 weeks after treatment. RESULTS: A total of 73 patients (Dysport, 38; Botox, 35) were entered. The Dysport group received a mean (SD) dose of 477 (131) (range 240-720) Dysport units, and the Botox group received a mean (SD) dose of 152 (45) (range 70-240) Botox units. The mean (SEM) post-treatment Tsui scores for the Dysport group (4.8 (0.3)) and the Botox group (5.0 (0.3)) were not statistically different (p=0.66). The study had 91% power to detect a clinically significant difference of two points. Both groups showed substantial improvement in Tsui score by week 2 (mean (SD); Dysport, 46 (28)%; Botox, 37 (28)%), with a peak effect at week 4 (mean (SD); Dysport, 49 (29)%; Botox, 44 (28)%). A similar response profile was seen for other assessments of efficacy. The duration of effect, assessed by time to retreatment, was also similar (mean (SD); Dysport, 83.9 (13.6) days; Botox, 80.7 (14.4) days; p=0.85). During the study 22 of 38 (58%) Dysport patients reported 39 adverse events, and 24 of 35 (69%) Botox patients reported 56 adverse events (p=0.35). A global assessment of efficacy and safety considered that 29 of 38 (76%) Dysport patients and 23 of 35 (66%) Botox patients were treatment successes (p=0.32). CONCLUSION: Patients with predominantly rotational cervical dystonia treated with the clinically indicated dose of Botox or three times that dose in Dysport units show similar improvements and do not have significantly different safety profiles.

Adult↗

Large-needle core biopsy: nonmalignant breast abnormalities evaluated with surgical excision or repeat core biopsy.

PURPOSE: To classify lesions initially considered nonmalignant at large-needle core biopsy that were subsequently surgically excised or sampled at repeat biopsy. MATERIALS AND METHODS: From August 1, 1991, to December 31, 1996, 1,032 breast abnormalities (214 malignant and 818 nonmalignant lesions) were sampled at large-needle core biopsy. Of the nonmalignant lesions, 112 (14%) abnormalities were studied. Twenty-four abnormalities were subsequently excised because of discordant imaging and pathologic findings; 41 may have been missed at biopsy (25 were surgically excised, and 16 were sampled at repeat biopsy); 40 were surgically excised as recommended by the pathologist; and seven were excised for other indications. RESULTS: None of 24 abnormalities excised because of discordant findings was malignant. Among the 41 possibly missed lesions, infiltrating ductal carcinoma was found in one lesion that was removed surgically and in one sampled at repeat biopsy. Among the 40 lesions recommended for excision by the pathologist, 16 malignancies were found (ductal carcinoma in situ, 11; infiltrating ductal carcinoma, three; phyllodes tumor, two). None of the remaining seven lesions was malignant. CONCLUSION: Correlation of the technical quality of the biopsy, imaging features, and pathologic findings resulted in 96 surgical excisions and 16 repeat biopsies of lesions initially considered nonmalignant. Eighteen additional malignancies were identified.

Biopsy, Needle↗

A telephone survey of the provision of palliative day care services.

A telephone survey was conducted to gather preliminary data in order to identify the nature of palliative day care provision in the UK. A random sample of 131 day centres was taken from 17 regional locations in the UK. providing a 60% representation out of a total of 215 adult day care facilities. A combination of a structured and semistructured interview schedule was used to collect the data. The results obtained from this preliminary survey provided further information on the nature, range, and types of services that are currently provided by UK palliative day care centres; management and organizational issues; and the nature of common problems and care issues of patients attending day centres. Data from the study provided further information on the current status of day care services. The implications for future evaluative research are discussed, particularly in the area of the impact and cost-effectiveness of day care services and the potential work with regard to different models of service provision.

Data Collection↗

Continuous improvement learning for residents.

Physicians must be ready to assume an active role in the design, implementation, and improvement of emerging models of health care delivery. Knowledge and skill in continuous improvement prepare them to engage seriously in the processes of change, on the basis of the same scientific principles they always have relied on in the use of evidence to improve outcomes. This includes include the ability to 1) identify the health needs of the individuals and communities for which they provide health services; 2) assess the impact of current practice with appropriate outcome measures; 3) discover what in the process of health care may be contributing to less than desired outcomes; 4) design and test interventions to change the process of care to improve outcomes; 5) act as an effective member of the interdisciplinary team required to complete these tasks; and 6) consider ethical principles and professional values when making decisions about change in health services delivery. Graduate medical education presents special opportunities and challenges for learning about continuous improvement. Early experiences at Rainbow Babies and Children's Hospital in Cleveland and Children's Hospital in Boston suggest how we might prepare pediatricians and other physicians to create positive change and continually improve health care.

Boston↗

A neural network approach to the analysis and classification of human craniofacial growth.

Planning of treatment in the field of orthodontics and maxillo-facial surgery is largely dependent on the individual growth of a patient. In the present work, the growth of 43 orthodontically untreated children was analysed by means of lateral cephalograms taken at the ages of 7 and 15. For the description of craniofacial skeletal changes, the concept of tensor analysis and related methods have been applied. Thus the geometric and analytical shortcomings of conventional cephalometric methods have been avoided. Through the use of an artificial neural network, namely self-organizing neural maps, the resultant growth data were classified and the relationships of the various growth patterns were monitored. As a result of self-organization, the 43 children were topologically ordered on the emerging map according to their craniofacial size and shape changes during growth. As a new patient can be allocated on the map, this type of network provides a frame of reference for classifying and analysing previously unknown cases with respect to their growth pattern. If landmarks are used for the determination of growth, the morphometric methods applied as well as the subsequent visualization of the growth data by means of neural networks can be employed for the analysis and classification of growth-related skeletal changes in general.

Adolescent↗

Which workers smoke?

OBJECTIVES: This article examines differences by occupation in daily cigarette smoking prevalence and intensity among full-time workers, and how these differences are associated with smoking restrictions at work. DATA SOURCES: Most of the data are from a Health Canada-sponsored Supplement to the 1994/95 National Population Health Survey (NPHS). The analysis is based on 5,674 respondents aged 15 to 64 who were full-time workers at the time of their interview. Comparable information is presented from the 1978/79 Canada Health Survey and the 1986 Labour Force Survey Smoking Supplement. MAIN RESULTS: In 1994/95, 28% of full-time workers were daily smokers, and about a third of them smoked 25 or more cigarettes a day. Smoking prevalence and intensity were lowest among white-collar workers and highest among blue-collar workers. Since 1978/79, there has been an overall decline in smoking prevalence, and since 1986, a decline in smoking intensity among all workers except those in outdoor blue-collar occupations. About 6 in 10 full-time workers who smoked daily encountered restrictions at work.

Adolescent↗

Cadmium toxicity and distribution in metallothionein-I and -II deficient transgenic mice.

To date, numerous correlative studies have implicated metallothionein in the detoxification of heavy metals and in the regulation of metal distribution within an organism. In the present study cadmium-binding proteins (metallothionein equivalents), cadmium acute toxicity, and cadmium distribution in tissues and subcellular fractions were compared in metallothionein-I and -II deficient (MT-/-) mice and the parental strain carrying intact metallothionein genes (MT+/+) to determine if the absence of metallothionein altered any of these parameters. In an uninduced state, MT-/- mice expressed lower levels of cadmium-binding proteins relative to MT+/+ mice in several tissues. Administration of zinc enhanced the levels of cadmium-binding proteins in liver, small intestine, kidney, pancreas, and male sex organs, but not in cecum or brain of MT+/+ mice compared to zinc pretreated MT-/- mice. The cadmium LD50 was similar for MT-/-, MT+/+, and zinc-pretreated MT-/- mice (15-17 mumol CdCl2/kg body weight delivered i.p.). However, zinc-pretreated MT+/+ mice had a cadmium LD50 of 58-63 mumol CdCl2/kg body weight. Over two-thirds of cadmium was found in liver, cecum, small intestine, and kidney in both MT+/+ and MT-/- mice; therefore, metallothionein levels do not appear to play a major role in the tissue distribution of cadmium. However, after zinc pretreatment, MT+/+ mice accumulated more cadmium in the liver and less in other tissues, whereas the amount of cadmium in the liver was not altered by zinc pretreatment in MT-/- mice. In general, the cytosolic/particulate ratio of cadmium was significantly higher in tissues of noninduced MT+/+ mice relative to MT-/- mice. This difference was accentuated after zinc pretreatment. Together these results indicate that basal levels of metallothionein do not protect from the acute toxicity of a single i.p. cadmium challenge. Furthermore, it does not appear that the cytosolic compartmentalization of cadmium is correlated with reduced toxicity.

Animals↗

Increasing popularity of injection as the route of administration of amphetamine in Edinburgh.

Six hundred and thirty four interviews of injecting drug users were performed between 1992 and 1994 as part of a study of injecting drug use and HIV prevalence in Edinburgh, Scotland. Amphetamine was injected by more subjects (44%) than any other drug. Preference for injection as the route of administration of amphetamine increased over the period despite no change in the popularity of the drug generally. Simultaneously, heroin use and injection declined. Analyses indicated that amphetamine injectors comprised two distinct sub-groups. The majority were polydrug injectors who injected frequently, had a longer injecting history and were more likely to share injection equipment. About one-fifth were stimulant-only injectors who injected infrequently, were relatively recent initiates to injecting and whose numbers increased over the 3 years. Drug treatment and prevention services may need to explore alternative methods to respond effectively to these emerging trends.

Adolescent↗

The increase in the induction of IL-2 expression with caloric restriction is correlated to changes in the transcription factor NFAT.

The objective of this study was to determine if the increase in the induction of interleukin-2 (IL-2) expression with caloric restriction correlates with changes in binding activity of the IL-2-specific transcription factor NFAT (nuclear factor of activated T cells) and/or the ubiquitous transcription factor AP-1 in T cells from male Fischer 344 rats. Splenic T cells were isolated from young (6-month) and old (24-month) rats fed ad libitum and from old (24-month) rats fed a restricted diet (40% caloric restriction) that began at 6 weeks of age. T cells were stimulated with concanavalin A (Con A) and the expression of IL-2 and the DNA binding activity of the transcription factors NFAT and AP-1 were measured in these cells. We found that the induction of IL-2 activity and mRNA levels decreased with age and that caloric restriction significantly (P < 0.05) reduced the age-related decline in IL-2 expression. The ability of nuclear extracts from T cells isolated from old rats fed ad libitum and restricted old rats to bind to the NFAT oligonucleotide or AP-1 oligonucleotide decreased with age. Caloric restriction significantly (P < 0.05) reduced the age-related decline in NFAT but had no significant effect on AP-1 binding activity. We also measured the induction of c-fos and c-jun expression by Con A in T cells from young and old rats fed ad libitum or caloric-restricted diet. The induction of c-fos protein and mRNA levels but not c-jun protein or mRNA levels decreased significantly with age. Caloric restriction significantly (P < 0.05) reduced the age-related decline in c-fos expression but had no significant effect on c-jun expression. Therefore, the increase in IL-2 expression with caloric restriction correlates with an increase in binding activity of transcription factor NFAT and an increase in the expression of c-fos, which is a component of the NFAT-protein complex.

Aging↗

Identification of integrin-stimulated sites of serine phosphorylation in FRNK, the separately expressed C-terminal domain of focal adhesion kinase: a potential role for protein kinase A.

Focal adhesion kinase (pp125(FAK)) is a protein tyrosine kinase that is localized to focal adhesions in many cell types and which undergoes tyrosine phosphorylation after integrin binding to extracellular matrix. In some cells the C-terminal non-catalytic domain of pp125(FAK) is expressed as a separate protein referred to as FRNK (FAK-related, non-kinase). We have previously shown that overexpression of FRNK inhibits tyrosine phosphorylation of pp125(FAK) and its substrates as well as inhibiting cell spreading on fibronectin. In this report we identify Ser148 and Ser151 as residues in FRNK that are phosphorylated after tyrosine phosphorylation of pp125(FAK) and in response to integrin binding to fibronectin. Tyrosine phosphorylation of pp125(FAK) appears to be an early event after integrin occupancy, and serine phosphorylation of FRNK occurs significantly later. Treatment of fibroblasts with a series of protein kinase A inhibitors delayed serine phosphorylation of FRNK as well as cell spreading on fibronectin and tyrosine phosphorylation of pp125(FAK). However, these PKA inhibitors are unlikely to delay cell spreading simply by preventing serine phosphorylation of FRNK, as overexpression of FRNK containing mutations of Ser148 and Ser151 either singly or jointly to either alanine or glutamate residues did not significantly alter the ability of FRNK to act as an inhibitor of pp125(FAK).

Animals↗