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Biomedical subjects

K Evans

Publications and source records attributed to K Evans.

At least 37 records · Page 2Linked to original sources

Community based universal neonatal hearing screening by health visitors using otoacoustic emissions.

OBJECTIVES: To carry out a pilot study to test the feasibility of health visitors (HVs) performing neonatal otoacoustic emissions (OAE) hearing screening in the community using Echoport ILO288 and to evaluate its acceptability to parents and HVs. DESIGN: Prospective cohort study. SETTING: Local health centres and babies' homes in urban and rural settings in West Gloucestershire. PARTICIPANTS: Twelve HVs, 683 babies, and their parents. MAIN OUTCOME MEASURES: Coverage rate, age at testing, referral rate for formal audiology testing, and parental anxiety scores. RESULTS: Of the 683 babies registered with the study HVs, 99% (675) were tested, with a median age at first test of 18 days. Parental consent for the study was refused for six of the eight not tested. Taking a unilateral pass as a screening pass (for comparison with other studies), 4% (27/675) failed the first OAE test, and 1.9% (13/675) failed a second OAE test performed by the HV within a further two weeks and were referred for formal audiology testing. One baby (0.15%) was found to have a moderate sensorineural hearing loss on brain stem auditory evoked responses, giving a false positive rate of 1.7% (12/675). Some 18% (120/675) were tested at home, of which 80% (96/120) were combined with another planned reason for HV contact. In all, 82% (555/675) of tests were carried out in health centre clinics, of which 47% (260/555) were combined purpose visits. Mean parental anxiety scores (possible range 0-5) were 0.86, 2.27, and 3.45 before the first test, first retest, and audiology test respectively. The median time taken for one HV to complete testing was 12.2 minutes (range 3-65), compared with the 15 minutes currently allocated for two HVs to perform distraction testing. Based on the results of questionnaires, the test was very well received by parents and HVs alike. CONCLUSION: HVs are able to perform OAE testing in the neonatal period at home and in local health centre clinics. They achieve high population coverage rates and low false positive rates. Universal neonatal hearing screening by HVs using OAE testing is feasible, well received, and could be less demanding of HV time than the current distraction testing. This model of universal neonatal hearing screening should be considered by the National Screening Committee.

Attitude to Health↗

A randomized controlled trial of community-oriented and hospital-oriented care for discharged psychiatric patients: influence of personality disorder on police contacts.

An important forensic psychiatric measure, contacts with police, was compared in a randomized, controlled trial of 155 patients with severe mental illness with a previous admission within the past two years. The patients, who also had their personality status addressed formally before randomization, were allocated to community multidisciplinary teams or to hospital-based care programs after discharge from in-patient care and were followed up for one year. A total of 138 patients (89%) had at least one post-baseline assessment and of these patients, 16 (12%) had at least one police contact in the year of the study, most of which were emergency assessments. The data showed significantly greater numbers of police contacts in patients with increasing severity of personality disturbance. Patients with such disturbance were six times more likely to have police contacts than those with no personality disorder. There were significantly more contacts in patients with borderline and antisocial (dissocial) personality disorder allocated to community-oriented care compared with hospital-oriented care. These findings have important implications for risk assessment in severe mental illness.

Adolescent↗

Carbohydrate and fat have different effects on plasma leptin concentrations and adipose tissue leptin production.

Leptin is secreted by adipocytes and plays a role in the regulation of food intake. However, the regulation of leptin production by adipose tissue is unclear. We have investigated whether a mixed meal or a high-fat load given orally, or a pure fat load given intravenously, stimulates adipose tissue leptin production. Six volunteers were studied on two occasions following an overnight fast. On one occasion they consumed tomato soup containing 40 g of triacylglycerol (as Intralipid) and 9.6 g of carbohydrate; on the other occasion Intralipid was infused intravenously over 4 h to give the same fat load. A further eight subjects consumed a mixed meal (containing 37 g of fat and 100 g of carbohydrate) after an overnight fast. Paired blood samples were obtained from an arterialized hand vein and a vein draining subcutaneous adipose tissue at baseline and for 6 h following the meals or the start of the infusion. After both the intravenous and oral fat loads, the arterialized and adipose venous plasma leptin concentrations decreased over 6 h (both P<0.001), as did the leptin veno--arterial difference (P=0.01). Following the mixed meal, there was a slight increase in the arterialized plasma leptin concentration (P=0.02) and a more marked increase in the adipose venous plasma leptin concentration (P=0.03) and in the adipose tissue leptin veno--arterial difference (P=0.01), all peaking at 240 min. We conclude that the increase in plasma leptin concentration observed after meals is not simply a result of an energy load, but is in response to a signal that is not present following a fat load without carbohydrate.

Adipose Tissue↗

Selective expansion of intraepithelial lymphocytes expressing the HLA-E-specific natural killer receptor CD94 in celiac disease.

BACKGROUND & AIMS: Celiac disease is a gluten-induced enteropathy characterized by the presence of gliadin-specific CD4(+) T cells in the lamina propria and by a prominent intraepithelial T-cell infiltration of unknown mechanism. The aim of this study was to characterize the subset(s) of intraepithelial lymphocytes (IELs) expanding during active celiac disease to provide insights into the mechanisms involved in their expansion. METHODS: Flow-cytometric analysis of isolated IELs and/or immunohistochemical staining of frozen sections were performed in 51 celiac patients and 50 controls with a panel of monoclonal antibodies against T-cell and natural killer (NK) receptors. In addition, in vitro studies were performed to identify candidate stimuli for NK receptor expression. RESULTS: In normal intestine, different proportions of IELs, which were mainly T cells, expressed the NK receptors CD94/NKG2, NKR-P1A, KIR2D/3D, NKp46, Pen5, or CD56. During the active phase of celiac disease, the frequency of CD94(+) IELs, which were mostly alphabeta T cells, was conspicuously increased over controls. In contrast, the expression of other NK markers was not modified. Furthermore, expression of CD94 could be selectively induced in vitro by T-cell receptor activation and/or interleukin 15, a cytokine produced by intestinal epithelial cells. CONCLUSIONS: The gut epithelium favors the development of T cells that express NK receptors. In active celiac disease, there is a specific and selective increase of IELs expressing CD94, the HLA-E-specific NK receptor that may be related to T-cell receptor activation and/or interleukin 15 secretion.

Adult↗

Protein machines and lipid assemblies: current views of cell membrane fusion.

Protein machines and lipid bilayers both play central roles in cell membrane fusion, a process crucial to life. Recent results provide clues to how both components function in fusion. Recent observations suggest a common mechanism by which very different fusion machines (from lipid-enveloped viruses and synaptic vesicles) may function to produce compartment-joining pores. This mechanism presumes that fusion proteins act as machines that use stored conformational energy to assemble closely juxtaposed lipid bilayers, bend these to form fusion-competent structures, stabilize unfavorable lipid structures and destabilize a committed intermediate to drive fusion pore formation.

Lipid Bilayers↗

Ethanol with a mixed meal increases postprandial triacylglycerol but decreases postprandial non-esterified fatty acid concentrations.

Plasma triacylglycerol concentrations increase after the acute ingestion of alcohol (specifically ethanol). However, the effect of ethanol when consumed with a mixed meal has not been well studied. The objective of the present study was to determine the perturbations of lipid metabolism that occur after ingestion of ethanol in combination with a mixed meal of specific fatty acid composition. Blood samples were taken from seven healthy male subjects before and after a mixed meal, with and without ethanol. The specific fatty acid composition of the test meal allowed the fatty acids to be traced into the plasma non-esterified fatty acid pool during the postprandial period. Statistical analysis by repeated measures ANOVA showed significant effects of ethanol. For example, postprandial lipaemia was enhanced after the ethanol test meal compared with the control (P < 0.05), mainly due to increases in triacylglycerol-rich lipoproteins in the flotation range Sf 60-400 (VLDL1) (P < 0.05); those in the range Sf 20-60 (VLDL2) and also Sf > 400 (chylomicrons) were not significantly affected. The later postprandial increase in plasma non-esterified fatty acid concentrations was reduced after the ingestion of ethanol (P < 0.001), but the proportions of palmitoleic acid (a marker of fatty acid content of the test meal) and of linoleic acid (a marker of endogenous lipolysis) were not affected. The results suggest a primary effect of ethanol on the stimulation of secretion of large VLDL particles, which then compete for clearance with chylomicrons by lipoprotein lipase. The results do not support an effect of ethanol on the release of non-esterified fatty acid into the plasma. The suppression of plasma non-esterified fatty acid concentrations during the postprandial period may contribute towards the beneficial effects of moderate ethanol consumption.

Adult↗

Pamidronate therapy as prevention of bone loss following renal transplantation.

BACKGROUND: Very rapid bone loss, osteopenia and skeletal morbidity after renal transplantation have been well documented and found to occur in a sex dependent fashion. Glucocorticoids, cyclosporine and pre-existing uremic osteodystrophy have been implicated in the pathogenesis of the skeletal lesions. Glucocorticoid induced osteopenia is also a serious clinical problem in patients with various nonrenal diseases and can be prevented, or at least attenuated, by pamidronate and other bisphosphonates. METHOD: We prospectively studied 26 male patients undergoing renal transplantation, and randomized them to receive either placebo or intravenous pamidronate (0.5 mg/kg) at the time of transplantation and again one month later. All patients received immunosuppression comprising prednisolone, cyclosporine and azathioprine. The bone mineral density (BMD) of the second, third and fourth lumbar vertebrae and of the femoral neck was measured at the time of transplantation and at three months and 12 months after transplantation using dual energy X-ray absorptiometry (DXA). RESULTS: Twelve months after transplantation, the mean (+/- SEM) BMD of the lumbar vertebrae in patients who received placebo had decreased 6.4% (P < 0.05). In contrast, patients who received pamidronate experienced no significant reduction of BMD at the lumbar vertebrae. At the femoral neck, placebo-treated patients showed a reduction of BMD of 9% (P < 0.005), whereas there was no significant change in the pamidronate treated group. The two study groups had similar patient profiles, serum parathyroid hormone (PTH) and aluminium concentrations. After transplantation, comparable falls in the serum creatinine and PTH concentration were found in the two groups. Apart from transient hypocalcemia in two patients, no significant adverse effects of pamidronate were noted. CONCLUSION: This study has shown that the early rapid bone loss that occurs in men during the first 12 months after renal transplantation can be prevented by two intravenous doses of pamidronate given at transplantation and one month later. The regimen was simple to administer, well tolerated and potentially applicable to other clinical groups of glucocorticoid treatment patients.

Absorptiometry, Photon↗

Pre-treatment EEG and it's relationship to depression severity and paroxetine treatment outcome.

An array of variables have been assessed as potential early predictors of antidepressant response in depressed patients. This exploratory study examined the relationship of clinical outcome, following pharmacotherapeutic treatment, with quantitative electroencephalographic (EEG) features assessed prior to treatment onset. In 70 major affective disorder patients, pre-treatment spectrum-analysed topographic EEG indices (absolute power, relative power, mean frequency, inter-hemispheric power asymmetry and coherence for 4 frequency bands) were assessed in relation to baseline HAM-D ratings and HAM-D rating changes following 6 weeks of open-label paroxetine treatment. EEG slow wave (theta) activities were positively correlated with depression ratings prior to treatment. Of the patients (n = 51) completing treatment, 80% evidenced a >50% reduction in HAM-D ratings. Improved rating changes in general were found to be negatively related to slow (delta and theta) wave activity and positively related to fast (beta) activity at frontal recording sites. Findings are discussed in relation to the neurochemistry and neurobiology of depressive disorders.

Adult↗

An in vivo comparison of the kinetics of protein and lipid deposition on group II and group IV frequent-replacement contact lenses.

PURPOSE: To investigate the degree and rate of deposition of protein and lipid on FDA group II and group IV contact lens materials over a period of up to 28 days of wear. METHODS: Twenty-two subjects wore a group IV lens (Acuvue) and a group II lens (Soflens 66) in a randomized, cross-over study. The lenses were randomly worn for periods between 1 and 28 days and then collected for laboratory-based deposition analysis. RESULTS: The group II lenses revealed an increased degree of lipoidal spoilage (p < 0.0001) and the group IV lenses exhibited increased protein spoilage (p < 0.0001). Surface protein for both materials reached a maximum after 1 day and did not increase over the 4-week wearing period (p = NS). Total protein for group IV lenses reached a maximum between 1 and 7 days and then reached a plateau, with no further increase occurring (p = NS), whereas total protein accumulation on the group II lens continued to increase across all time periods (p < 0.05). Lipid deposition on the group IV lens was maximal after 1 day and increased no further (p = NS), whereas lipid deposition on the group II material monotonously increased and progressively built-up over the 4 weeks of wear (p < 0.0001). CONCLUSIONS: The kinetics of contact lens deposition is mediated by the chemical structure of the contact lens material under consideration. Protein deposition occurs rapidly with group IV materials before reaching a maximum, whereas N-vinyl pyrrolidone-containing group II materials progressively accumulate protein and lipid deposits, with no plateau occurring.

Adult↗

Who cares? A focus group study on follow up care after discharge from hospital.

AIM: To ascertain general practitioners', patients' and hospital staff's perspectives on post discharge problems and other problems related to hospital liaison in the Darwin urban area. To identify stakeholders who have a role in addressing these problems and develop locally appropriate responses to improve post hospital discharge patient care. METHOD: A qualitative study using three focus groups was conducted with seven GPs, six ex-patients of the study hospital and 11 hospital staff. The problems and proposed strategies identified by these groups were then fed back to stakeholders for comment in order to generate recommendations to improve post discharge care. RESULTS: The main themes generated were: lack of recognition of the potential role of the GP and patient by the hospital; poor communication between the hospital, GPs and patients; and, lack of resources to improve information flow. Specifically, 'not being listened to' by hospital doctors, nurses and GPs was a major theme of the patient focus group and was equated with a 'not caring' attitude by some hospital staff and GPs. Twelve strategies were generated by the focus groups with considerable overlap of issues. The main strategies were aimed at GP liaison by providing GPs and patients with timely, adequate and comprehensible information as part of their 'duty of care'. General practitioners, however, need to provide legible, relevant and concise referral letters to facilitate this process. CONCLUSIONS: This study highlights the need for improved communication between the GP and the hospital to redress the lack of recognition of GPs. The appointment of a GP/hospital liaison officer in the study hospital could address this issue as well as others of patient empowerment and advocacy, and partnerships in health care. This project has also highlighted the importance of consulting patients and the value of their perspective to complement GP and hospital viewpoints.

Aftercare↗

North Carolina macular dystrophy (MCDR1) locus: a fine resolution genetic map and haplotype analysis.

PURPOSE: We previously reported linkage of North Carolina macular dystrophy in a single isolated family to a broad region on chromosome 6q16. In order to refine the localization of the MCDR1 gene (North Carolina macular dystrophy), additional families with this disease and new markers were studied. METHODS: We ascertained 10 families with the North Carolina macular dystrophy phenotype (MCDR1). These families were of various ethnic and geographic origins such as Caucasian, Mayan Indian, African-American, French, British, German, and American of European decent. Two hundred thirty-two individuals in these families underwent comprehensive ophthalmic examinations and blood was collected for genotyping. One hundred seventeen were found to be affected. Linkage simulation studies were performed. Two-point linkage, haplotype analysis, and multipoint linkage was performed using VITESSE and FASTLINK. HOMOG was used to test for genetic heterogeneity. RESULTS: The clinical features were consistent with the diagnosis of North Carolina macular dystrophy in all families. Multipoint linkage analysis indicates that the MCDR1 gene is in the interval between D6D249 and D6S1671 with a maximum LOD score of 41.52. There was no evidence of genetic heterogeneity among the families studied. Families 765, 768, 772, 1193, and 1292 shared the same chromosomal haplotype in this region. CONCLUSIONS: This is the largest single data set of families with the MCDR1 phenotype. The single large family from North Carolina continues to be informative for the closest flanking markers and alone supports the minimal candidate region as suggested by previous studies. There remains no evidence of genetic heterogeneity in this disease. Most of the American families appear to have descended from the same ancestral mutation. The remaining families could each represent independent origins of the mutation in the MCDR1 gene.

Adolescent↗

The MexA-MexB-OprM multidrug efflux system of Pseudomonas aeruginosa is growth-phase regulated.

Intrinsic antibiotic resistance in Pseudomonas aeruginosa is attributed to low outer membrane permeability and drug efflux mediated by the products of mexAmexBoprM efflux operon. Using a mexA-phoA fusion, expression of the efflux genes was assessed as a function of growth in a variety of strains. The efflux operon was growth-phase regulated in both wild-type and nalB strains, being minimally expressed in lag phase and increasing in log to late log phase. MexR, the only known regulator of MexAMexBOprM and target of mutation in nalB strains, was not involved in the growth-phase regulation. The las cascade regulates genes based on increased cell-density, but a deletion in lasR had no effect on mexAmexBoprM expression. Putative recognition sequences for AlgT/U and RpoN were identified upstream of mexA, but algT/U and rpoN null mutants also had no effect on mexAmexBoprM expression.

Bacterial Outer Membrane Proteins↗

Manual-assisted cognitive-behaviour therapy (MACT): a randomized controlled trial of a brief intervention with bibliotherapy in the treatment of recurrent deliberate self-harm.

BACKGROUND: The treatment of deliberate self-harm (parasuicide) remains limited in efficacy. Despite a range of psychosocial, educational and pharmacological interventions only one approach, dialectical behaviour therapy, a form of cognitive-behaviour therapy (CBT), has been shown to reduce repeat episodes, but this is lengthy and intensive and difficult to extrapolate to busy clinical practice. We investigated the effectiveness of a new manual-based treatment varying from bibliotherapy (six self-help booklets) alone to six sessions of cognitive therapy linked to the booklets, which contained elements of dialectical behaviour therapy. METHODS: Thirty-four patients, aged between 16 and 50, seen after an episode of deliberate self-harm, with personality disturbance within the flamboyant cluster and a previous parasuicide episode within the past 12 months, were randomly assigned to treatment with manual-assisted cognitive-behaviour therapy (MACT N = 18) or treatment as usual (TAU N = 16). Assessment of clinical symptoms and social function were made at baseline and repeated by an independent assessor masked to treatment allocation at 6 months. The number and rate of all parasuicide attempts, time to next episode and costs of care were also determined. RESULTS: Thirty-two patients (18 MACT; 14 TAU) were seen at follow-up and 10 patients in each group (56% MACT and 71% TAU) had a suicidal act during the 6 months. The rate of suicidal acts per month was lower with MACT (median 0.17/month MACT; 0.37/month TAU; P = 0.11) and self-rated depressive symptoms also improved (P = 0.03). The treatment involved a mean of 2.7 sessions and the observed average cost of care was 46% less with MACT (P = 0.22). CONCLUSIONS: Although limited by the small sample, the results of this pilot study suggest that this new form of cognitive-behaviour therapy is promising in its efficacy and feasible in clinical practice.

Adolescent↗

Effects of an oral and intravenous fat load on adipose tissue and forearm lipid metabolism.

We have studied the fate of lipoprotein lipase (LPL)-derived fatty acids by measuring arteriovenous differences across subcutaneous adipose tissue and skeletal muscle in vivo. Six subjects were fasted overnight and were then given 40 g of triacylglycerol either orally or as an intravenous infusion over 4 h. Intracellular lipolysis (hormone-sensitive lipase action; HSL) was suppressed after both oral and intravenous fat loads (P < 0.001). Insulin, a major regulator of HSL activity, showed little change after either oral or intravenous fat load, suggesting that suppression of HSL action occurred independently of insulin. The rate of action of LPL (measured as triacylglycerol extraction) increased with both oral and intravenous fat loads in adipose tissue (P = 0.002) and skeletal muscle (P = 0.001). There was increased escape of LPL-derived fatty acids into the circulation from adipose tissue, shown by lack of reesterification of fatty acids. There was no release into the circulation of LPL-derived fatty acids from skeletal muscle. These results suggest that insulin is not essential for HSL suppression or increased triacylglycerol clearance but is important in reesterification of fatty acids in adipose tissue but not uptake by skeletal muscle, thus affecting fatty acid partitioning between adipose tissue and the circulation, postprandial nonesterified fatty acid concentrations, and hepatic very low density lipoprotein secretion.

Adipose Tissue↗

A program of acquired immune deficiency syndrome education for nurses in Romania.

After the fall of the communist government in Romania, many children were found to be human immunodeficiency virus (HIV) infected. The majority of these children were abandoned and currently live in orphanages. The children have been cared for on a day-to-day basis by nurses with little general nursing education and even less HIV education. The Romanian-American Pediatric AIDS Education and Clinical Research Program was established at Texas Children's Hospital and Baylor College of Medicine in May, 1996 to aid in the education of Romanian nurses. Syllabi developed by the U.S. nursing team were initially piloted in three pediatric HIV centers in Romania in July, 1997. Since that time, two annual nursing symposia have been held offering topics on general pediatrics and HIV-related content. The purpose of this article is to describe a program of HIV education for nurses in Romania.

Child↗

Quorum-sensing and siderophore biosynthesis in Pseudomonas aeruginosa: lasR/lasI mutants exhibit reduced pyoverdine biosynthesis.

Cell density-dependent gene expression in Pseudomonas aeruginosa is controlled, in part, by the quorum-sensing regulator LasR. lasR null mutants exhibited a reproducible 2-fold decrease in production of the catecholate-hydroxamate siderophore pyoverdine during grown under iron-limiting conditions. Similarly, lasI mutants defective in the biosynthesis of the autoinducer PAI-1 also exhibited a 2-fold decrease in pyoverdine production which could be largely restored upon addition of exogenous PAI-1. lasR mutants were not altered with respect to expression of the pvdD gene involved in the synthesis of the peptide portion of pyoverdine, indicating that some other pyoverdine biosynthetic gene(s) were affected by the LasRI status of the cell. This represents the first report of quorum-sensing regulation of siderophore production in bacteria and highlights the fact that cell density, while not an essential signal for pyoverdine expression, does enhance production of this siderophore.

Bacterial Proteins↗