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M Ryan

Publications and source records attributed to M Ryan.

At least 55 records · Page 3Linked to original sources

Indexing-based differential display--studies on post-mortem Alzheimer's brains.

In this study we demonstrate for the first time that a novel indexing-based differential display technique generates valid and reproducible results when applied to human post-mortem tissue. We studied expression profiles in prefrontal cortex tissue derived from Alzheimer's disease (AD) and control brains, respectively, and found robust changes in several expressed genes, some of which have a known association with the disease process in AD. These included the dramatic reduction of calcineurin (known to be involved in tau phosphorylation) and GAP-43 (associated with synapse remodelling). Differential display results were confirmed by semi-quantitative RT-PCR on a larger number of brains.

Aged↗

SDS-induced phenoloxidase activity of hemocyanins from Limulus polyphemus, Eurypelma californicum, and Cancer magister.

Phenoloxidase, widely distributed among animals, plants, and fungi, is involved in many biologically essential functions including sclerotization and host defense. In chelicerates, the oxygen carrier hemocyanin seems to function as the phenoloxidase. Here, we show that hemocyanins from two ancient chelicerates, the horseshoe crab Limulus polyphemus and the tarantula Eurypelma californicum, exhibit O-diphenoloxidase activity induced by submicellar concentrations of SDS, a reagent frequently used to identify phenoloxidase activity. The enzymatic activity seems to be restricted to only a few of the heterogeneous subunits. These active subunit types share similar topological positions in the quaternary structures as linkers of the two tightly connected 2 x 6-mers. Because no other phenoloxidase activity was found in the hemolymph of these animals, their hemocyanins may act as a phenoloxidase and thus be involved in the primary immune response and sclerotization of the cuticle. In contrast, hemolymph of a more recent arthropod, the crab Cancer magister, contains both hemocyanin with weak phenoloxidase activity and another hemolymph protein with relatively strong phenoloxidase activity. The chelicerate hemocyanin subunits showing phenoloxidase activity may have evolved into a separate phenoloxidase in crustaceans.

Animals↗

Rhinocerebral zygomycosis in childhood acute lymphoblastic leukaemia.

The hazards associated with invasive candidiasis and aspergillosis in oncology patients are well recognised. These conditions typically present late in treatment, often after prolonged or recurrent episodes of neutropenia. We report the occurrence of Absidia corymbifera infection causing rhinocerebral zygomycosis in two children with acute lymphoblastic leukaemia, early in the induction phase of treatment and within a 3-month interval, in the same oncology unit. The initial presentation of facial pain was rapidly followed by the development of cranial nerve palsies, cavernous sinus thrombosis, diabetes insipidus, seizures and death within 9 days of symptom onset, despite aggressive management with high-dose liposomal amphotericin (Ambisome), surgical debridement and local instillation of amphotericin solution. These cases highlight the need for awareness of zygomycosis as a potentially lethal fungal infection that can present even with short duration exposure to the usual risk factors. Their occurrence within a limited time period raises questions as to the relative importance of environmental exposure. The failure of medical and surgical intervention to impact on the course illustrates the need to develop appropriate preventative strategies which may have to incorporate measures to reduce the environmental exposure of susceptible patients.

Absidia↗

Minimally invasive, radioguided surgery for primary hyperparathyroidism.

BACKGROUND: Primary hyperparathyroidism affects 1 in 700 individuals in the United States. A single adenoma is responsible in over 85% of cases. Surgery remains the most effective treatment. This study was designed to assess the feasibility of minimally invasive radioguided parathyroidectomy (MIRP) with confirmation of excision by ex vivo radioactivity alone. METHODS: Seventy-five consecutive patients with primary hyperparathyroidism were prospectively studied. Following sestamibi scan, patients underwent unilateral neck exploration guided by a handheld gamma probe, which was also used to measure ex vivo radioactivity of excised tissue. RESULTS: The sestamibi scan was positive in 88% of the patients. A small incision (mean, 3.2+/-0.3 cm) was sufficient. Ectopic gland sites were localized in five patients with positive scans and single adenomas. Mean operative time was 48 minutes (range, 15-125 minutes), with shorter procedures after the initial 20 cases (mean, 24 vs. 72 minutes; P < .01). Radioguided parathyroidectomy was successful in 97%, with a mean follow-up of 11 months (range, 1-26 months). As noted previously, adenomatous parathyroid glands contained more than 20% of the background radioactivity. CONCLUSIONS: MIRP is a feasible alternative to bilateral dissection with the advantages of guided dissection and rapid confirmation, and may become the procedure of choice for primary hyperparathyroidism.

Adenoma↗

Gene expression profiling in the post-mortem human brain--no cause for dismay.

Global expression profiling techniques such as microarray technology promise to revolutionize biology. Soon it will be possible to investigate alterations at the transcript level of the entire human genome. There is great hope that these techniques will at last shed light on the pathological processes involved in complex neuropsychiatric disorders such as schizophrenia. These scientific advances in turn have re-kindled a great interest and demand for post-mortem brain tissue. Good quality post-mortem tissue undoubtedly is the fundamental prerequisite to investigate complex brain disorders with molecular profiling techniques. In this review we show that post-mortem brain tissue can yield good quality mRNA and intact protein antigens which allow the successful application of traditional molecular biology methods as well as novel profiling techniques. We also consider the use of laser-capture microdissection on post-mortem tissue. This recently developed technique allows the experimenter to explore the molecular basis of cellular function at the single cell level. The combination of laser-capture microdissection with high throughput profiling techniques offers opportunities to obtain precise genetic fingerprints of individual neurons allowing comparisons of normal and pathological states.

Autopsy↗

Retroviral vector-mediated expression of HoxB4 in hematopoietic cells using a novel coexpression strategy.

Retroviral vector-mediated expression of the homeoboxgene, HoxB4, in hematopoietic cells has been reported to mediate a benign expansion of gene-modified hematopoietic stem and precursor cells in vivo. In the present study, we used a novel coexpression strategy for coordinated expression of HoxB4 along with a cytoplasmic protein from a retroviral vector. The novel coexpression strategy, based on cotranslational protein separation mediated by the 2A sequence of foot-and-mouth disease virus (FMDV), allows an indirect quantification of HoxB4 expression levels when inserting a reporter such as the enhanced green fluorescent protein (GFP) in the retroviral vector. Presence of the 2A sequence did not interfere with the correct subcellular localization of HoxB4 (nuclear) and GFP (cytoplasmic), nor with the titer of bicistronic vectors, and mediated functional long-term coexpression (at least 1 year) of GFP and HoxB4 after transplantation of transduced mouse bone marrow cells in mice.

Animals↗

Costs and benefits of cervical screening IV: valuation by women of the cervical screening programme.

OBJECTIVES: To assess the value of the cervical smear test to women, taking account of the positive and negative aspects of the cervical screening service. DESIGN: A postal survey. SETTING: Tayside Health Board region of Scotland. PARTICIPANTS: A sample of 2000 women aged 20-59. MAIN OUTCOME MEASURES: Maximum willingness to pay (WTP) for a cervical smear test. RESULTS: Women were prepared to pay 50.20 British pounds per smear on a 3-yearly basis. Willingness to pay was positively related to income, but unrelated to age and whether or not the respondent had previously had a smear. CONCLUSIONS: Previous studies have estimated the cost per screen or cost per life year saved by cervical screening. This study used the economic instrument of WTP to take account of other potential (dis)benefits to women. The value women place on having a smear was more than the cost to the National Health Service (NHS) of providing the service. The output of a WTP study is potentially useful at the policy level. Future work should explore both the value of alternative approaches to cervical screening, and the value of competing health care interventions.

Adolescent↗

Assessing women's preferences for intrapartum care.

BACKGROUND: Recent government reports have recommended involving consumers in the planning of health services. Although satisfaction surveys have traditionally been used, they have several limitations. This paper describes a relatively new method of eliciting consumer preferences that allows respondents (women) to indicate the importance that they attribute to specific aspects of a service. The aim was to explore the feasibility of using a discrete choice experiment to assess the importance to women of different aspects of intrapartum care. METHODS: In this pilot study of 301 women at low obstetric risk, data were collected using an anonymous self-complete questionnaire given to each participant by the midwife at the booking visit. RESULTS: The results of the regression model suggest that respondents prefer maternity units that offer greater continuity of caregiver, more methods of pain relief, continuous fetal heart rate monitoring, a homely appearance, routine involvement of medical staff, and greater involvement for the woman in the decision-making process. Although all attributes were important to women, they were not all of equal importance. For example, if continuity of caregiver were achieved at the expense of decreasing the availability of pain relief then women would be worse off. CONCLUSIONS: The discrete choice experiment appears to be a useful tool in assessing the strength of women's preferences for different aspects of maternity care. Future research should include a qualitative approach to explore in greater depth the processes involved in shaping women's preferences.

Adult↗

Efficacy of an angiotensin II receptor antagonist in managing hyperaldosteronism.

OBJECTIVE: To determine whether an angiotensin II receptor antagonist decreases blood pressure in patients with hyperaldosteronism and hypertension who are taking other antihypertensive agents. DESIGN: A double-blind randomized placebo-controlled crossover study. PATIENTS AND METHODS: Blood pressure and hormonal responses to 2-week courses of placebo/irbesartan (150 mg/day given by mouth at 08.05 h) were assessed in 10 patients with hyperaldosteronism. Clinic blood pressure was measured by sphygmomanometer, and plasma concentrations of aldosterone, cortisol, angiotensin II, electrolytes and renin activity (PRA) were determined weekly. Automated 24 h ambulatory blood pressure recordings were made at the end of the active and placebo phases. RESULTS: Irbesartan caused a post-dose decrease in ambulatory blood pressure (systolic, P = 0.02; diastolic, P = 0.05) in the period from 10.00 h to 20.00 h. Clinic blood pressure, measured at trough, was not significantly decreased. Plasma aldosterone decreased (P < 0.03) and PRA increased (P < 0.04) in the first week of active treatment with irbesartan, but differences between the placebo and active-treatment groups were not significant in the second week. There were no significant changes in plasma concentrations of angiotensin II, cortisol or potassium in either week. In the second week of irbesartan treatment, there were associations between change in plasma aldosterone and maximal change in ambulatory blood pressure (systolic and diastolic). CONCLUSION: Irbesartan has a role in combination antihypertensive treatment of patients with hyperaldosteronism.

Adult↗

Can obstetric complications explain the high levels of obstetric interventions and maternity service use among older women? A retrospective analysis of routinely collected data.

OBJECTIVE: To determine whether the higher levels of obstetric intervention and maternity service use among older women can be explained by obstetric complications. DESIGN: A retrospective analysis of routinely collected data from the Aberdeen Maternity and Neonatal Databank. PARTICIPANTS: All residents of Aberdeen city district delivering singleton infants at the Maternity Hospital 1988-1997 (28,484 deliveries). MAIN OUTCOME MEASURES: Odds ratios for each intervention in older maternal age groups compared with women aged 20-29. Interventions considered include obstetric interventions (induction of labour, augmentation, epidural use, assisted delivery, caesarean section) and raised maternity service use (more than two prenatal scans, amniocentesis, antenatal admission to hospital, admission at delivery of more than five days, infant resuscitation, and admission to the neonatal unit). METHODS: Logistic regression was used to investigate the association between maternal age and the incidence of interventions. The odds ratios for each intervention were then adjusted for relevant obstetric complications and maternal socio-demographic characteristics. RESULTS: Levels of amniocentesis, caesarean section, assisted delivery, induction, and augmentation (in primiparae) are all higher among older women. Maternity service use also increases significantly with age: older women are more likely to have an antenatal admission, more than two scans, a hospital stay at delivery of more than five days, and have their baby admitted to a neonatal unit. Controlling for relevant obstetric complications reveals several examples of effect modification, but does not eliminate the age effect for most interventions in most groups of women. CONCLUSIONS: Higher levels of intervention among older women are not explained by the obstetric complications we considered.

Adult↗

Use of discrete choice experiments to elicit preferences.

This paper considers the application of discrete choice experiments for eliciting preferences in the delivery of health care. Drawing upon the results from a recently completed systematic review, the paper summarises the application of this technique in health care. It then presents a case study applying the technique to rheumatology outpatient clinics. 200 patients were questioned about the importance of six attributes: staff seen (junior doctor or specialist nurse); time in waiting area; continuity of contact with same staff; provision of a phone-in/advice service; length of consultation; and change in pain levels. The systematic review indicated that discrete choice experiments have been applied to a wide number of areas and a number of methodological issues have been addressed. Consistent with this literature, the case study found evidence of both rationality and theoretical validity of responses. The approach was used to establish the relative importance of different attributes, how individuals trade between these attributes, and overall benefit scores for different clinic configurations. The value of attributes was estimated in terms of time, and this was converted to a monetary measure using the value of waiting time for public transport. Discrete choice experiments represent a potentially useful instrument for eliciting preferences. Future methodological work should explore issues related to the experimental design of the study, methods of data collection and analysis, and satisfaction with the economic axioms of the instrument. Collaborative work with psychologists and qualitative researchers will prove useful in this research agenda.

Adolescent↗

Doxycycline dosing.

Explore the source record for details and available documents.

Anti-Bacterial Agents↗

Eliciting public preferences for healthcare: a systematic review of techniques.

BACKGROUND: Limited resources coupled with unlimited demand for healthcare mean that decisions have to be made regarding the allocation of scarce resources across competing interventions. Policy documents have advocated the importance of public views as one such criterion. In principle, the elicitation of public values represents a big step forward. However, for the exercise to be worthwhile, useful information must be obtained that is scientifically defensible, whilst decision-makers must be able and willing to use it. AIMS AND OBJECTIVES: The aim was to identify techniques that could be reasonably used to elicit public views on the provision of healthcare. Hence, the objectives were: (1) to identify research methods with the potential to take account of public views on the delivery of healthcare; (2) to identify criteria for assessing these methods; (3) to assess the methods identified according to the predefined criteria; (4) to assess the importance of public views vis-à-vis other criteria for setting priorities, as judged by a sample of decision-makers; (5) to make recommendations regarding the use of methods and future research. METHODS: A systematic literature review was carried out to identify methods for eliciting public views. Criteria currently used to evaluate such methods were identified. The methods identified were then evaluated according to predefined criteria. A questionnaire-based survey assessed the relative importance of public views vis-à-vis five other criteria for setting priorities: potential health gain; evidence of clinical effectiveness; budgetary impact; equity of access and health status inequalities; and quality of service. Two techniques were used: choice-based conjoint analysis and allocation of points technique. The questionnaire was sent to 143 participants. A subsample was followed up with a telephone interview. RESULTS: The methods identified were classified as quantitative or qualitative. RESULTS - QUANTITATIVE TECHNIQUES: Quantitative techniques, classified as ranking, rating or choice-based approaches, were evaluated according to eight criteria: validity; reproducibility; internal consistency; acceptability to respondents; cost (financial and administrative); theoretical basis; whether the technique offered a constrained choice; and whether the technique provided a strength of preference measure. Regarding ranking exercises, simple ranking exercises have proved popular, but their results are of limited use. The qualitative discriminant process has not been used to date in healthcare, but may be useful. Conjoint analysis ranking exercises did well against the above criteria. A number of rating scales were identified. The visual analogue scale has proved popular within the quality-adjusted life-year paradigm, but lacks constrained choice and may not measure strength of preference. However, conjoint analysis rating scales performed well. Methods identified for eliciting attitudes include Likert scales, the semantic differential technique, and the Guttman scale. These methods provide useful information, but do not consider strength of preference or the importance of different components within a total score. Satisfaction surveys have been frequently used to elicit public opinion. Researchers should ensure that they construct sensitive techniques, despite their limited use, or else use generic techniques where validity has already been established. Service quality (SERVQUAL) appears to be a potentially useful technique and its application should be researched. Three choice-based techniques with a limited application in healthcare are measure of value, the analytical hierarchical process and the allocation of points technique, while those more widely used, and which did well against the predefined criteria, include standard gamble, time trade-off, discrete choice conjoint analysis and willingness to pay. Little methodological work is currently available on the person trade-off. RESULTS - QUALITATIVE TECHNIQUES: Qualitative techniques were classified as either individual or group-based approaches. Individual approaches included one-to-one interviews, dyadic interviews, case study analyses, the Delphi technique and complaints procedures. Group-based methods included focus groups, concept mapping, citizens' juries, consensus panels, public meetings and nominal group techniques. Six assessment criteria were identified: validity; reliability; generalisability; objectivity; acceptability to respondents; and cost. Whilst all the methods have distinct strengths and weaknesses, there is a lot of ambiguity in the literature. Whether to use individual or group methods depends on the specific topic being discussed and the people being asked, but for both it is crucial that the interviewer/moderator remains as objective as possible. The most popular and widely used such methods were one-to-one interviews and focus groups. (ABSTRACT TRUNCATED)

Data Collection↗

Liver toxicity. Could this be a drug reaction?

BACKGROUND: Adverse reaction to prescription medications, over the counter medications and complementary medicines, are an important cause of liver toxicity. OBJECTIVE: To highlight the importance of drug induced liver toxicity in patients presenting with abnormal liver function tests. DISCUSSION: In patients who present with symptoms of liver dysfunction such as anorexia, itch or Jaundice and in whom liver function tests are abnormal, the possibility of an adverse reaction to medications should be considered. A detailed history of all medications taken in the past few months, including complementary medicines, should be obtained. After exclusion of other causes of liver disease such a viral hepatitis or gallstones, the cessation of the offending medication and the normalisation of liver tests is usually sufficient to establish a diagnosis. Occasionally, referral to a specialist and liver biopsy may be required.

Adult↗