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Biomedical subjects

M Evans

Publications and source records attributed to M Evans.

At least 37 records · Page 2Linked to original sources

Synthesis and degradation of sodium iron phosphate glasses and their in vitro cell response.

The degradation profiles of six sodium iron phosphate glass formulations have been investigated using simple dissolution trials in deionized water. The glasses were produced from the appropriate phosphate salts by melting at 1200 degrees C in 5% Au/95% Pt crucibles. Dissolution rates varied from 0.2 gcm(-2)h(-1) for the 1% Fe glass to essentially zero over the 6-week test period for the 15% Fe and 20% Fe glasses. The overall degradation rate was found to vary according to the approximate relation: rate = 1.3e(-0.79x) gcm(-2)h(-1), where x is the percentage iron content of the glass. Glasses with 10% or greater iron content were observed to maintain a constant density over the course of the tests and thus appeared to degrade from the surface and not the bulk. In vitro cell response tests were conducted on the glasses using macrophages and primary craniofacial osteoblasts. These tests were performed on the glasses with 10% or greater iron content because glasses with lower iron content degraded too quickly. Confocal microscopy revealed a rounded macrophage morphology and IL-1beta production was low, suggesting little macrophage activation. However, a significant level of peroxide production was observed. Osteoblasts were observed to attach to the glass surfaces and spread, exhibiting a similar cytosketetal organization to the cells on the Thermanox controls, with a high level of F-actin organization. On balance, the 15% Fe glass performed slightly better than the 20% Fe glass in these assays.

Animals↗

The public health response to a case of Lassa fever in London in 2000.

OBJECTIVES: Evaluation of the Department of Health 1996 guidance, the Memorandum on the Management and Control of Viral Haemorrhagic Fevers. METHODS: Description of the public health management in 2000 of the fifth UK patient confirmed to have Lassa fever. RESULTS: Delayed risk categorisation of the patient occurred for a variety of reasons. DH Guidance was followed once infection control advice was sought. Active surveillance of 125 contacts was extremely resource intense, involving over 3000 communications. Self-monitoring by healthcare workers should be considered in future. Advice on use of ribavirin prophylaxis is not included in the Memorandum, nor advice or templates for information sheets for contacts. Information sheets are now available from the Health Protection Agency in the event of future cases. International aspects not adequately addressed include the need for reliable risk assessment to be carried out before patients are medically evacuated from the country of origin, and the steps required to repatriate UK nationals. Effective and efficient communication is required between national and international organisations involved in such incidents. CONCLUSIONS: If guidelines are unclear or impracticable they will not be followed. It is important that lessons are learned and documented and that national guidance be regularly reviewed.

Communicable Disease Control↗

Burden and cost of imported infections admitted to infectious diseases units in England and Wales in 1998 and 1999.

BACKGROUND: International travel from the UK has been rising, and the number of imported infections has increased. This study aimed to describe the number, nature, origin, clinical burden and cost of imported infections treated in infectious disease units (IDU) in England and Wales. METHOD: Information about all admissions in 1998 and 1999 with illnesses considered to have been acquired during their most recent travel abroad was collected retrospectively by IDUs using a pre-piloted questionnaire. RESULTS AND ANALYSIS: Four of the 23 IDUs in England and Wales were able to complete the questionnaires. They reported a total of 421 travel related admissions during the 2-year period. Three hundred and ninety-two of these cases were attributed to infectious causes, and of these a discharge diagnosis was made for 340 cases. The total number of bed days used to treat cases of imported infection was 2918. The most common diagnosis was malaria. The odds ratio that cases of imported infection were malaria was highest following visits to Africa. The average cost per bed day on the IDUs was around pound sterling 100, and on this basis, the total cost of treating imported infections on the four IDUs in 2 years was around pound sterling 289,000. The relative risk of acquiring an imported infection requiring treatment on an IDU was greatest for travellers to Africa. CONCLUSIONS: From this study, the estimate of the total annual cost of IDU treatment for imported infections in England and Wales is in excess of pound sterling 800,000. Many cases may be preventable with prophylactic medication and vaccination and travel advice on risk reduction. Further information about imported infections would be useful to inform travel medicine services, other clinicians and travellers about the health risks associated with travel to specific areas, and help to target and assess the cost effectiveness of preventative measures.

Adult↗

Assessing mental health in primary care research using standardized scales: can it be carried out over the telephone?

BACKGROUND: Telephone interviewing has economic and logistical advantages but has not been widely used in the UK. Most studies comparing face-to-face and telephone psychiatric assessment have been carried out in the US, often restricted to a population with known psychiatric disorder and involving comparisons between two separate sample groups rather than repeat interviews with the same group. The aim of the present study was to compare face-to-face and telephone administration of the 12-item General Health Questionnaire and the Revised Clinical Interview Schedule in a UK general practice sample. METHOD: Ninety-eight consecutive attenders at two general practices were assessed twice within 48 h. The order of face-to-face and telephone interviews was alternated. RESULTS: There was no evidence that the mode of administration led to a bias in scores on the CIS-R. For the GHQ, those aged over 60 tended to score higher on the telephone. There was good agreement between face-to-face and telephone scores for both GHQ and CIS-R and good agreement for case definition. Participants had a strong preference for face-to-face interviews. CONCLUSIONS: Telephone assessment of mental health using the GHQ and CIS-R is a reasonable method to be used in primary care research in the UK with the limitation that telephone responses from older people might be different from face-to-face assessments for the GHQ. However, telephone interviewing appeared less acceptable and should probably be used in the context of established or ongoing personal contact between researcher and subject.

Adolescent↗

Chylomicron-remnant-like particles modify production of vasoactive mediators by endothelial cells.

Endothelial-cell dysfunction is a critical initiating event in the pathogenesis of atherosclerosis. Although there is evidence to suggest that chylomicron remnants (CMRs), lipoproteins derived from the diet, influence endothelial-cell function to generate a pro-atherogenic phenotype, the mechanisms involved remain undefined. We have examined the effects of CMR-like particles (CMR-LPs) on human endothelial-cell function, focusing on the cyclo-oxygenase (COX) and nitric oxide synthase (NOS) pathways. CMR-LPs strongly enhanced the expression of the inducible cyclo-oxygenase COX-2 and increased prostacyclin synthesis in a biphasic manner. Studies with the COX-2-selective inhibitor NS-398 confirmed the COX-2 dependency of the later increase in prostanoid production. Pre-incubation with CMR-LPs reduced basal and thrombin-stimulated cGMP generation, whereas expression of endothelial NOS was not modified by remnant treatment.

6-Ketoprostaglandin F1 alpha↗

Characteristics of a human monoclonal autoantibody to the thyrotropin receptor: sequence structure and function.

The properties of a human monoclonal antibody to the thyrotropin receptor (TSHR) (M22) with the characteristics of patient sera thyroid stimulating autoantibodies is described. Similar concentrations (pmol/L) of M22 Fab and porcine TSH had similar stimulating effects on cyclic adenosine monophosphate (cAMP) production in TSHR-transfected Chinese hamster ovary cells whereas higher doses of intact M22 immunoglobulin G (IgG) were required to cause the same level of stimulation. Patient sera containing TSHR autoantibodies with TSH antagonist (blocking) activity inhibited M22 Fab and IgG stimulation in a similar way to their ability to block TSH stimulation. Thyroid-stimulating monoclonal antibodies (TSmAbs) produced in mice inhibited 125I-TSH binding and 125I-M22 Fab binding to the TSHR but the mouse TSmAbs were less effective inhibitors than M22. These competition studies emphasized the close relationship between the binding sites on the TSHR for TSH, TSHR autoantibodies with TSH agonist activity, and TSHR autoantibodies with TSH antagonist activity. Recombinant M22 Fab could be produced in Escherichia coli and the recombinant and hybridoma produced Fabs were similarly active in terms of inhibition of TSH binding and cAMP stimulation. The crystal structure of M22 Fab was determined to 1.65 A resolution and is that of a standard Fab although the hypervariable region of the heavy chain protrudes further from the framework than the hypervariable region of the light chain. The M22 antigen binding site is rich in aromatic residues and its surface is dominated by acidic patches on one side and basic patches on the other in agreement with an important role for charge-charge interactions in the TSHR-autoantibody interaction.

Animals↗

Human monoclonal thyroid stimulating autoantibody.

A monoclonal autoantibody (MAb) with powerful thyroid stimulating activity has been produced from lymphocytes from a patient with Graves' disease. The autoantibody and its Fab fragment bind to the thyroid stimulating hormone (TSH) receptor (TSHR) with high affinity, inhibit labelled TSH binding to the receptor and stimulate cyclic AMP production in Chinese hamster ovary cells transfected with TSHR. TSHR autoantibodies with TSH agonist or antagonist activities from patients' serum samples are effective inhibitors of labelled monoclonal autoantibody binding to TSHR. Thus, the human monoclonal autoantibody has all the characteristics of serum TSHR autoantibodies. Its availability has important implications for new studies on the pathogenesis of Graves' disease.

Antibodies, Monoclonal↗

Co-infection by a yeast-like organism in Hematodinium-infected European edible crabs Cancer pagurus and velvet swimming crabs Necora puber from the English Channel.

During the winter months, edible crabs Cancer pagurus and velvet swimming crabs Necora puber from the English Channel can harbour infections by a Hematodinium sp. dinoflagellate. This parasite is responsible for a highly pathological condition known as 'Pink Crab Disease' (PCD) in the edible crab. In the current study, a high proportion (between 25 and 100%) of Hematodinium-infected edible and velvet swimming crabs captured from 2 sites in the English Channel also harboured a systemic infection by a yeast-like organism. This is the first report of such an infection in crabs. Budding yeast-like cells were observed intracellularly in circulating haemocytes and free in the host plasma. These cells stained positively with silver and periodic acid-Schiff (PAS) reactions. Despite an apparent haemocytopoenia in Hematodinium-infected crabs, haemocytic encapsulation of yeast-like cells was evident, while no such response was observed against Hematodinium sp. plasmodia. It is hypothesised that Hematodinium infection in these crabs may either increase the likelihood of secondary infections via an indirect suppression of the host immune system, or alternatively, decrease the likelihood of competitive growth inhibition by stimulating the host immune system to encapsulate and destroy secondary pathogens. Results are discussed with regard to the likely identity of the yeast-like organism, and the role of secondary pathogens in the eventual mortality of Hematodinium-infected hosts.

Animals↗

Dimensional vs. categorical diagnosis in psychosis.

OBJECTIVE: To compare dimensional measures vs. categorical diagnosis of psychopathology in their prediction of disability and outcome in psychotic illness. METHOD: A community study of 980 subjects with psychotic illness was included in the Australian National Survey of Mental Health and Wellbeing. The study instrument [including the Schedules for Clinical Assessment in Neuropsychiatry (SCAN)] yielded symptom data along with Operational Criteria for Psychotic Illness (OPCRIT) diagnoses by several diagnostic schemata. Factor analysis of symptoms yielded five dimensions of psychopathology (positive symptoms, negative symptoms, dysphoria, mania and substance use). Variance in service demand and disability explained by the diagnostic schemata was compared with the variance explained by the dimensions of psychopathology. RESULTS: Dimensional measures of psychopathology explained more of the variance in service demand, dysfunctional behaviour, social adaptation and global occupation and function. Only use of support services and illness course were better predicted by categorical diagnosis. Dimensional scores explained significant extra variance when added to categorical diagnoses. CONCLUSION: Dimensional measures of psychopathology explain more variance in behaviour, disability and outcome than does categorical diagnosis in functional psychosis. Dimensions provided significant extra information not provided by diagnosis and would be a more useful basis for clinical management.

Adult↗

Effects of insulin lispro and chronic vitamin C therapy on postprandial lipaemia, oxidative stress and endothelial function in patients with type 2 diabetes mellitus.

BACKGROUND: Insulin therapy may influence cardiovascular disease (CVD) and lipid metabolism in type 2 diabetes (T2D). Exaggerated postprandial lipaemia (PPL) is a feature of diabetic dyslipidaemia affecting CVD via enhanced oxidative stress (OS) and endothelial dysfunction. We assessed endothelial function and OS during PPL following insulin and vitamin C. Twenty (17 M) T2D patients were studied (mean Hba1c 8.4%) at baseline, following 6 weeks of insulin lispro (0.2 Iu kg-1) and vitamin C 1-g daily. Eight-h lipid and glucose profiles were measured following a fatty meal. Endothelial function (flow-mediated vasodilatation: FMD) and OS were measured at fasting, 4 h and 8 h. MATERIALS AND METHODS: Glucose, body mass index, and total and LDL cholesterol remained unchanged. FMD improved. Placebo group: fasting, 1.1 +/- 1.2 to 4.2 +/- 1.1% (P < 0.001); 4-h, 0.3 +/- 1.2 to 3.1 +/- 0.9% (P < 0.01); 8-h, 0.7 +/- 1.1 to 3.76 +/- 1.1% (P < 0.001). Vitamin C group: fasting, 0.9 +/- 1.1 to 6.1 +/- 1.3% (P < 0.001); 4-h, 0.7 +/- 1.5 to 4.9 +/- 2.1% (P < 0.001); 8-h, 0.8 +/- 0.9 to 5.8 +/- 0.6% (P < 0.01). Post-prandial lipaemia was attenuated: TG area-under-curve (mmol L-1 8 h-1), 52.6 +/- 11 to 39.1 +/- 12.5 (placebo group), P < 0.02; and 56.9 +/- 8 to 40.1 +/- 10.3 (vitamin C group), P < 0.02. Oxidative stress was reduced, with greater changes in the vitamin C group. CONCLUSION: Insulin may thus exert vascular benefits in T2D, by modifying fasting and postprandial lipid metabolism resulting in reduced OS and improved EF. Vitamin C therapy may augment the vascular benefits of insulin in T2D through additional effects on OS and EF.

Adult↗

Kikuchi-Fujimoto disease: a rare but important cause of lymphadenopathy.

UNLABELLED: Cervical lymphadenopathy is a common problem in children. Kikuchi-Fujimoto disease (histiocytic necrotizing lymphadenitis) is a rare condition that causes persistent lymphadenopathy and has a characteristic histological appearance. Kikuchi-Fujimoto disease is well recognized in Japan, where it was first described, but descriptions in the paediatric literature are sparse. Paediatricians may therefore be unaware of this rare but important condition. The case is described of a 14-y-old girl suffering from fatigue, weight loss, night sweats and lymphadenopathy. The predominance of systemic symptoms prompted an extensive investigation. The diagnosis of Kikuchi-Fujimoto disease was made after direct histological examination of a lymph node biopsy. The case illustrates the clinical features of this little-known condition and highlights the potential confusion with other diagnoses. The pathological features are discussed and the literature reviewed. CONCLUSION: Kikuchi-Fujimoto disease should be considered in cases of persistent lymphadenopathy. An early biopsy can be instrumental in preventing unnecessary investigations and potentially harmful treatments.

Adolescent↗

Coping effectiveness training reduces depression and anxiety following traumatic spinal cord injuries.

OBJECTIVE: To extend the findings of a pilot study that evaluated a brief group-based psychological intervention aimed at improving psychological adjustment, self-perception and enhancing adaptive coping following spinal cord injury. The theoretical underpinnings of the Coping Effectiveness Training (CET) Programme are Lazarus and Folkman's (1984) cognitive theory of stress and coping, and cognitive behavioural therapy techniques. DESIGN: A controlled trial comparing patients that received the CET intervention with matched controls on measures of psychological adjustment and coping. METHOD: A total of 45 intervention group participants and 40 matched controls were selected from inpatients at a hospital-based spinal cord injury centre. Outcome measures of anxiety and depression, self-perception and coping were collected before, immediately after and 6 weeks following the intervention. RESULTS: Intervention group participants showed a significant reduction in depression and anxiety, compared to the matched controls following the intervention. There was no evidence of a significant change in the pattern of coping strategies used by the intervention group compared to controls. The intervention group alone completed measures of self-perception. There was a significant decrease in the discrepancy between participants' 'ideal' self and 'as I am', and between 'as I would be without the injury' and 'as I am' following the intervention and at follow-up. Significant correlations were also found between self-perception, and anxiety and depression over time. CONCLUSIONS: These results confirm the findings of the pilot study, that the CET intervention facilitated a significant improvement in psychological adjustment to spinal cord injury. It is proposed that this improvement may be understood in terms of changing participants' negative appraisals of the implications of spinal cord injury with the result of increasing the perceived manageability of its consequences. Such decatastrophizing alters appraisals which are associated with current mood. Participants found shared discussion and problem-solving to be particularly helpful. Avenues for further research are discussed.

Adaptation, Psychological↗

Ultrasound imaging for external-beam prostate treatment setup and dosimetric verification.

Ultrasound (US) image-guided patient positional verification was performed daily on four prostate cancer patients using the BAT system (NOMOS Corporation, CA). The BAT system has shown that the prostate can shift by as much as 1 cm from its intended position in any direction. Furthermore, the daily shifts measured by the BAT system were included into the treatment planning system to assess changes in prostate dose coverage. Dose volume histograms were used to compare the dosimetry between the ideal patient set-up situation (prostate always positioned correctly) and that taking all patient daily shifts into consideration. Daily patient shifts on the order of magnitudes measured, can significantly and adversely affect dosimetric coverage, therefore an US-based patient positioning system is required for improving the therapeutic ratio.

Humans↗

Mechanisms involved in the resistance of Enterococcus faecalis to calcium hydroxide.

AIM: This study sought to clarify the mechanisms that enable E. faecalis to survive the high pH of calcium hydroxide. METHODOLOGY: E. faecalis strain JH2-2 was exposed to sublethal concentrations of calcium hydroxide, with and without various pretreatments. Blocking agents were added to determine the role of stress-induced protein synthesis and the cell wall-associated proton pump. RESULTS: E. faecalis was resistant to calcium hydroxide at a pH of 11.1, but not pH 11.5. Pre-treatment with calcium hydroxide pH 10.3 induced no tolerance to further exposure at pH 11.5. No difference in cell survival was observed when protein synthesis was blocked during stress induction, however, addition of a proton pump inhibitor resulted in a dramatic reduction of cell viability of E. faecalis in calcium hydroxide. CONCLUSIONS: Survival of E. faecalis in calcium hydroxide appears to be unrelated to stress induced protein synthesis, but a functioning proton pump is critical for survival of E. faecalis at high pH.

Calcium Hydroxide↗

The influence of the Pro12Ala mutation of the PPAR-gamma receptor gene on metabolic and clinical characteristics in treatment-naïve patients with type 2 diabetes.

Peroxisome proliferator activated receptor-gamma is an important factor in adipocyte differentiation and energy metabolism and is thus a candidate gene for obesity, insulin resistance and dyslipidaemia. We therefore assessed the associations between the most common variant of the PPAR-gamma, the Pro12Ala (P12A) substitution in the PPAR-gamma 2 gene, with BMI, blood pressure, fasting plasma glucose, HbA1c, total cholesterol, LDL and HDL cholesterol and plasma triglyceride in 183 treatment-naïve patients with type 2 diabetes (T2D). The P12A allele associated with lower fasting plasma glucose but had no influence on HbA1c or BMI. In obese patients (BMI > 29 kg/m2), the P12A substitution associated with elevated total and non-HDL cholesterol levels.

Adult↗

Isolation and characterization of human monoclonal autoantibodies to glutamic acid decarboxylase.

Production of human monoclonal autoantibodies to glutamic acid decarboxylase M(r) 65,000 (GAD65), characterization of their isotype, binding affinity, V region sequences and competition with autoantibodies in patients' sera is described. Lymphocytes from a patient with Addison's disease who had GAD65 autoantibodies without diabetes were immortalised and fused to a mouse/human hybridoma. In addition, mouse monoclonal antibodies to GAD65 were produced using standard techniques. F(ab')2S from our monoclonals and the GAD6 mouse monoclonal were used in competition with intact monoclonals and sera from diabetic patients for binding to 125I-labelled GAD65 (amino acids 46-586). Reactivities of the human monoclonals with GAD 65,000/67,000 M(r) chimeras were also studied. Variable region genes of human monoclonals were sequenced and analysed. The human monoclonals (n = 3) had affinity constants for GAD65 of 2.2 x 10(9), 5.8 x 10(9), 1.3 x 10(10) mol/l(-1); affinities of the mouse monoclonals (n = 5) ranged from 1.1 x 10(8) to 5.4 x 10(10) mol/l(-1). The binding of each of the human monoclonals was inhibited by GAD6 F(ab')2 and the binding of GAD6 antibody was inhibited by the human monoclonal F(ab')2S suggesting that the epitopes for these antibodies were overlapping. Studies with GAD65/GAD67 chimeras indicated that the human monoclonals reacted with C-terminal epitopes. The human monoclonals, GAD6 and 3/5 mouse monoclonals inhibited serum autoantibody binding to 125I-labelled GAD65. Overall, the human monoclonals were of high affinity, reacted with C-terminal epitopes and showed evidence of antigen driven maturation; they represented only a proportion of the repertoire of autoantibodies to GAD65 in the donor's serum and in the sera of patients with type-1 diabetes.

Addison Disease↗