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Biomedical subjects

C Ricketts

Publications and source records attributed to C Ricketts.

At least 19 recordsLinked to original sources

Common variations in the ALMS1 gene do not contribute to susceptibility to type 2 diabetes in a large white UK population.

AIMS/HYPOTHESIS: Alström syndrome is a rare monogenic disorder characterised by retinal dystrophy, deafness and obesity. Patients also have insulin resistance, central obesity and dyslipidaemia, thus showing similarities with type 2 diabetes. Rare mutations in the ALMS1 gene cause severe gene disruption in Alström patients; however, ALMS1 gene polymorphisms are common in the general population. The aim of our study was to determine whether common variants in ALMS1 contribute to susceptibility to type 2 diabetes in the UK population. METHODS: Direct sequencing was performed on coding regions and intron/exon boundaries of the ALMS1 gene in 30 unrelated probands with type 2 diabetes. The linkage disequilibrium (LD; D' and r2) and haplotype structure were examined for the identified variants. The common (minor allele frequency [MAF] >5%) single-nucleotide polymorphisms tagging the common haplotypes (tagged SNPs [tSNPs]) were identified and genotyped in 1985 subjects with type 2 diabetes, 2,047 control subjects and 521 families. RESULTS: We identified 18 variants with MAF between 6 and 38%. Three SNPs efficiently tagged three common haplotypes (rs1881245, rs3820700 and rs1320374). There was no association (all p > 0.05) between the tSNPs and type 2 diabetes in the case-control study and minor alleles of the tSNPs were not overtransmitted to probands with type 2 diabetes in the family study. CONCLUSIONS/INTERPRETATION: Common variations in the ALMS1 gene were not associated with type 2 diabetes in a large study of a white UK population.

Adult↗

Tear film lipid layer thickness and ocular comfort after meibomian therapy via latent heat with a novel device in normal subjects.

AIM: This study measures changes in tear film lipid layer thickness (LLT) and ocular comfort in normal subjects after 10 min use of a novel device, which delivers meibomian therapy with latent heat. The device is designed to promote the release of meibomian sebum into the tear film by delivering latent heat to the eyelids, thus thickening the lipid layer. Normal lid movements are maintained, facilitating resurfacing of the tear film. METHOD: A prospective, controlled, observer masked, single intervention trial in which 24 normal subjects were randomised into three groups. Group I underwent 10 min treatment with the activated device, Group II used the inactivated device for the same duration of time, and Group III had no intervention. The LLT of each subject was measured with a Keeler Tearscope prior and subsequent to the 10-min period. Subjective alteration in ocular comfort was also assessed. RESULTS: Seven of eight subjects (87.5%) in Group I exhibited an increase in LLT. The mean LLT in this group showed a statistically significant increase (left eyes 1.0 levels, P<0.001, right eyes 0.9 levels, P<0.003) compared to Groups II and III. Six of eight subjects (75%) using the activated device experienced subjective improvement in ocular comfort. CONCLUSION: Meibomian therapy with this device increases LLT in normal individuals. This implies a more stable tear film, reflected in subjective improvement in ocular comfort.

Adult↗

The effect of reporting speed on plain film reporting errors.

AIM: To determine whether reporting plain films at faster rates lead to a deterioration in accuracy. METHODS: Fourteen consultant radiologists were asked to report a total of 90 radiographs in three sets of 30. They reported the first set at the rate they would report normally and the subsequent two sets in two thirds and one half of the original time. The 90 radiographs were the same for each radiologist, however, the order was randomly generated for each. RESULTS: There was no significant difference in overall accuracy for each of the three film sets (p=0.74). Additionally no significant difference in the total number of false-negatives for each film set was detected (p=0.14). However, there was a significant decrease in the number of false-positive reports when the radiologists were asked to report at higher speeds (p=0.003). CONCLUSIONS: When reporting accident and emergency radiographs increasing reporting speed has no overall effect upon accuracy, however, it does lead to less false-positive reports.

Clinical Competence↗

Age-related temporal processing speed deterioration in auditory cortex.

A common problem among the elderly is a difficulty in discriminating speech sounds. One factor that may contribute to this is a deterioration in the ability to process dynamic aspects of speech such as formant transitions. For the aging auditory system, this deterioration in temporal processing speed may be manifest as a deficit in encoding time-varying sounds that contain rapidly changing frequencies such as formant transitions. The primary goal of this study was to explore the neural basis of the effects of aging on temporal processing speed. To this end, single units were recorded from the auditory cortex of young and aged rats in response to frequency-modulated (FM) sweeps that changed from trial to trial in both direction and speed. Results showed that the majority of cells recorded from young rats responded most vigorously to fast and medium speeds. By contrast, the majority of units recorded from aged animals responded best to slow speeds. For preferred direction of FM sweep, similar results were observed for both age groups, namely, approximately half of the units exhibited a direction-selective response. The results of the present study demonstrate an age-related decrease in the rate of change of frequency that can be processed by the auditory cortex.

Aging↗

Pre-registration diploma students: a quantitative study of entry characteristics and course outcomes.

Nurse education has been transformed over the last decade and continuing change is likely. Nurse educators are responsible for meeting the quality assurance standards of local stakeholders and student retention and progress are important aspects of this process. As part of a monitoring exercise, an enquiry was set up to review pre-registration selection and recruitment strategies and to establish if there were any significant relationships between the characteristics of pre-registration diploma entrants and their academic achievement or completion rates. A multi-factorial tree-based technique was used for this purpose. This is one of the first British studies to consider both academic performance and completion rates for pre-registration diploma students. Four cohorts (N = 355) were studied. There was marked heterogeneity in student characteristics with a wide age distribution, a significant proportion of mature entrants with previous care experience, and considerable diversity in terms of education. Education and age were significant predictors of academic achievement: entrants with a minimum of two A levels and mature women with recent study experience did particularly well. Younger recruits with modest educational qualifications on entry performed less well in their assessments of theoretical knowledge. Younger students tended to leave more regularly, and well-qualified entrants showed a greater tendency to complete, although these relationships were not statistically significant. Multi-factorial analysis demonstrated that organisational and course characteristics have a conjoint influence on course outcomes. Although the study is concerned with Project 2000 in the United Kingdom, there are lessons to be drawn concerning the selection and support of non-traditional recruits into nursing.

Achievement↗

Responses to time-varying stimuli in rat auditory cortex.

Responses to frequency modulated (FM) sweeps were recorded in rat primary auditory cortex. Forty-four percent of the cells were direction-selective. For speed selectivity, the majority of the cells preferred faster sweeps. The results suggest that rat auditory cortex may be used for processing communication signals of their predators or for detecting spectral changes in acoustic signals.

Acoustic Stimulation↗

The distribution of leukaemia in association with domestic water quality in south west England.

This study assessed whether there is any variation in the incidence of haematological malignancies between geographical areas of differing water supplies in the South West peninsula of the United Kingdom (1984 to 1988 inclusive). The possibility of correlations existing between variation in water quality and variation in the incidence of haematological malignancies was examined. Haematological incidence data, taken from the Leukaemia Research Fund's Data Collection Study, were mapped into 46 geographical areas of differing water supply. The distribution of the mapped cases was then tested for homogeneity using the Potthoff and Whittinghill (1966) test score. The age-adjusted incidence ratios calculated during the heterogeneity testing were examined for correlations with water quality indicators using correlation and stepwise regression. Significant heterogeneity in the incidence rates among water supply areas was observed for two groups of disease-acute leukaemias and myeloproliferative disorders. Three water quality indicators-pH, nitrate concentration and aluminium concentration-varied considerably over the study period. Significant correlations were observed between the standardized incidence ratios of five disease categories and some water quality indicators, especially aluminium and trihalomethane concentrations. The standardized incidence ratios of some haematological malignancies differed between geographical areas of water supply in South West England, and the evidence suggests that this variation may be associated with variation in water quality indicators. Although this lends support to similar findings in the United States of America, the pattern of correlations are affected by disease latency and statistical methodology.

England↗

Predicting outcome in severe ulcerative colitis.

BACKGROUND: Simple criteria are needed to predict which patients with severe ulcerative colitis will respond poorly to intensive medical treatment and require colectomy. AIMS: To find out if the early pattern of change in inflammatory markers or other variables could predict the need for surgery and to evaluate the outcome of medical treatment during one year follow up. PATIENTS: 51 consecutive episodes of severe colitis (Truelove and Witts criteria) affecting 49 patients admitted to John Radcliffe Hospital, Oxford. METHODS: Prospective study monitoring 36 clinical, laboratory, and radiographic variables. All episodes treated with intravenous and rectal hydrocortisone and 14 of 51 with cyclosporine. RESULTS: Complete response in 21 episodes (< or = 3 stools on day 7, without visible blood), incomplete response in 15 (> 3 stools or visible blood on day 7, but no colectomy), and colectomy on that admission in 15. During the first five days, stool frequency and C reactive protein (CRP) distinguished between outcomes (p < 0.00625, corrected for multiple comparisons) irrespective of whether patients or the number of episodes were analysed. It could be predicted on day 3, that 85% of patients with more than eight stools on that day, or a stool frequency between three and eight together with a CRP > 45 mg/l, would require colectomy. For patients given cyclosporine, four of 14 avoided colectomy but two continued to have symptoms. After admission, complete responders remained in remission for a median nine months and had a 5% chance of colectomy. Incomplete responders had a 60% chance of continuous symptoms and 40% chance of colectomy. CONCLUSIONS: After three days intensive treatment, patients with frequent stools (> 8/day), or raised CRP (> 45 mg/l) need to be identified, as most will require colectomy on that admission. The role of cyclosporine for treating severe colitis has yet to be defined. After seven days' treatment, patients with > 3 stools/day of visible blood have a 60% chance of continuous symptoms and 40% chance of colectomy in the following months.

Adult↗

Benefits and weaknesses of a cardiac rehabilitation programme.

The British Heart Foundation and the Chest, Heart and Stroke Association have allocated funds to develop cardiac rehabilitation programmes. We have recently completed and now evaluate an exercise-based rehabilitation course reinforced with advice about return to normal activity for 110 patients who had suffered acute myocardial infarction. Patients admitted to the Plymouth cardiac care unit were randomised into groups: a control group to receive standard hospital care, and a rehabilitation group who, in addition, received an exercise programme reinforced with advice. Patients were assessed at entry to the study and at intervals thereafter. Assessment was by questionnaire and objective tests consisting of a 12-minute walking test and weekly outpatient pedometry. In the rehabilitation group patients were able to walk further and faster, return to work earlier, undertake more housework, and resume normal sexual activity; they were less short of breath and did not experience more angina. However, the rehabilitation course brought little benefit to the patients' perception of well-being and their anxiety about health or their outlook on life. Exercise and advice are important components of a rehabilitation programme, but more attention needs to be given to the psychological aspects of recovery from a heart attack.

Adult↗

Binding of serum ferritin to concanavalin A: patients with homozygous beta thalassaemia and transfusional iron overload.

Serum ferritin concentrations have been measured in 124 patients with homozygous beta thalassaemia who were between 2 and 21 years old, had received 11--504 units of blood but had not undergone splenectomy. There were highly significant correlations between serum ferritin concentration and both the amount of blood transfused and alanine amino-transferase (ALT) activity. However, multivariate analysis showed that units of blood and ALT activity together only accounted for about 30% of the variation in serum ferritin concentration. Little of the remaining variation could be explained by other variables related to iron metabolism or liver damage. The concentration of concanavalin A binding ferritin increased rapidly with the number of units of blood up to 100 units but thereafter showed no further increase with number of transfusions. The concentration of non-binding ferritin was more closely related to transfusion load. These results suggest that the secretion of glycosylated ferritin from reticuloendothelial cells reaches a maximum with increasing iron accumulation, perhaps reflecting a maximum rate of synthesis. Ferritinaemia in patients with transfusional iron overload therefore seems to be the result of the combined effects of increased ferritin synthesis and the release of intracellular ferritin from damaged cells. A simple relationship between serum ferritin and iron stores cannot be assumed when ferritin concentrations exceed 4000 microgram/l or in patients who have received more than 100 units of transfused blood.

Adolescent↗

Erythropoiesis and iron metabolism in Hodgkin's disease.

Recently developed techniques for the investigation of iron kinetics were used to study the disturbance of iron metabolism in 19 untreated patients with Hodgkin's diseases (HD). The erythroid abnormality in newly diagnosed HD appears to be confined to those patients with systemic symptoms of weight loss, night sweats and fever, and consists of depression of marrow erythroid activity. These patients had a significnatly lower haemoglobin and serum iron concentration and a higher serum ferritin concentration, both when compared to normal subjects and to those patients with HD who lacked systemic symptoms. Ineffective erythropoiesis and red-cell destruction were not significantly increased. The present findings, confirm that HD patients with systemic symptoms have a depression of erythropoiesis, and that in these patients the marrow fails to respond to the stimulus of mild anaemia.

Adolescent↗

Erythropoiesis, iron stores and tissue iron exchange in man.

1. The exchange of iron between plasma and erythroid and non-erythroid tissues was measured in 14 normal subjects, 17 iron-deficient patients, nine patients with primary idiopathic haemochromatosis and in 13 patients with haemolytic disorders. 2. The two main factors determining tissue iron turnover were shown to be the level of iron stores and the erythropoietic activity of the bone marrow.

Adult↗

An evaluation of two methods of laboratory quality control.

Two methods for quality control of automated blood counters have been compared: (1) monitoring results from patients' samples, and (2) analysis of results of a stable whole-blood control. The latter method proved better able to distinguish calibration changes from patient variation.

Erythrocyte Indices↗

Measurement of haemolysis in patients with prosthetic heart valves.

Haemolysis following prosthetic heart valve insertion can be precisely and sensitively measured by means of a 59Fe ferrokinetic technique. Results obtained in a small series of patients with either Starr-Edwards or Brunwald-Cutter valve replacement are presented.

Aortic Valve↗

Studies in desferrioxamine and ferrioxamine metabolism in normal and iron-loaded subjects.

Plasma concentrations of desferrioxamine and ferrioxamine were measured following bolus injections of desferrioxamine and during 24 h infusions of the drug. [59Fe]ferrioxamine clearance and urinary iron excretion were also measured. Higher plasma ferrioxamine concentrations were found in iron loaded subjects and higher desferrioxamine concentrations in subjects with normal ironloads. There is a correlation between the circulating concentration of ferrioxamine during an infusion and the 48 h urinary iron excretion. The data suggests that the amount of iron chelated in vivo is related to an increase in the size of an intermediate chelatable pool rather than the total amount of the iron load. The well-recognized delay in urinary iron excretion appears to be related to active tubular reabsorption of ferrioxamine.

Blood Transfusion↗

A method for the investigation of reticuloendothelial iron kinetics in man.

A colloidal suspension of hydrolysed radio-iron of high specific activity has been developed for the investigation of reticuloendothelial (RE) iron kinetics in man. Following intravenous injection this material is cleared rapidly by the RE system and the iron released intn to the endogenous RE iron load, and it has proved possible to measure RE iron release without disturbing the normal iron flow.

Anemia, Hypochromic↗

Variability of serum ferritin concentration in normal subjects.

Serum ferritin concentrations were measured in normal subjects over periods of 1 day, 1 week and 7 weeks. The variation of the results was compared with variation of control of control sera. In most of the subjects the variation in the results could be attributed to the variation in the method of measurement. No diurnal variation in serum ferritin concentration was observed.

Circadian Rhythm↗