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Biomedical subjects

M Ryan

Publications and source records attributed to M Ryan.

At least 91 records · Page 5Linked to original sources
PubMed1999

The confirmation and control of metabolic caffeine in standardbred horses after administration of theophylline.

The origin of caffeine detections in equine serum and urine after theophylline administrations was examined. Three different preparations containing theophylline were administered to standardbred mares. Both blood and urine samples were collected. Caffeine was detected and quantified in theophylline administration samples by high performance liquid chromatography (HPLC) and liquid chromatography-tandem mass spectrometry (LC-MS-MS). Further in vitro analysis showed that caffeine metabolites were not detected when caffeine, or caffeine-containing products, were added to urine. Data derived from HPLC-UV and LC-MS-MS analysis of dosages of theophylline and caffeine are used to propose the establishment of a threshold limit to control and discern between metabolic and administered caffeine concentrations. A serum caffeine concentration of 250 ng/mL and a urine caffeine concentration of 1000 ng/mL are suggested. Based on the data supplied, these threshold concentrations could effectively control orally administered caffeine in racehorses, up to the dosage used in this work, up to 72 h before sampling time.

Animals↗
PubMed1999

A controlled study of the effects of isosorbide mononitrate on arterial blood pressure and pulse wave form in systolic hypertension.

OBJECTIVE: To determine the effect of an extended-release nitrate preparation on the arterial pulse wave and blood pressure of patients in whom systolic blood pressure was elevated in part by exaggerated pulse-wave reflectance. DESIGN: A double-blind randomized placebo-controlled crossover study was carried out. PATIENTS AND METHODS: The subjects were ten elderly patients with systolic hypertension resistant to conventional anti-hypertensive therapy. Pharmacodynamic responses to 2-week courses of placebo/isosorbide mononitrate (ISMN) were assessed in seven subjects by an ambulatory blood pressure monitor, and in all ten subjects by standard sphygmomanometry, arterial pulse-wave analysis and measurement of plasma nitrate concentration during peak and trough. RESULTS: Ambulatory systolic blood pressure was decreased by ISMN (P < 0.02) between 1000 and 2200 h. Ambulatory diastolic blood pressure fell with ISMN (P < 0.01) during the last 4 h of this period. At peak plasma nitrate levels, ISMN decreased the aortic systolic blood pressure (P < 0.01), ejection peak (P < 0.02) and augmentation component (P < 0.001) of the pulse wave; heart rate increased slightly (P < 0.03). CONCLUSION: ISMN has a role as an adjunct in the anti-hypertensive therapy of patients with refractory systolic hypertension due to exaggerated pulse-wave reflectance.

Aged↗
PubMed1999

Influence of angiotensin converting enzyme (ACE) genotype on interpretation of diagnostic tests for serum ACE activity.

BACKGROUND: The discovery that an insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene influences the circulating concentration of ACE may have implications for the proper use of serum ACE activity measurements in screening for sarcoidosis. AIM: To determine whether the sensitivity of the serum ACE test improves if ACE genotype is taken into account. METHODS: A retrospective determination of ACE genotype and clinical diagnosis was done in 54 patients with serum ACE activity above the upper limit of the reference range for the insertion (II) genotype. ACE was measured by radioenzymatic and spectrophotometric techniques, and genotype by PCR. RESULTS: When serum ACE values determined diagnostically were related to the appropriate genotype-specific reference range, sensitivity and specificity for diagnosis of sarcoidosis were 65-70% and 58% respectively, compared to 47-57% and 77% with a reference range unsegregated for genotype. CONCLUSION: ACE genotyping may be helpful in determining the diagnostic significance of mildly elevated serum ACE activity in patients with the II and ID genotypes.

Female↗
PubMed1999

An estimate of the proportion of diarrhoeal disease episodes seen by general practitioners attributable to rotavirus in children under 5 y of age in England and Wales.

Mean weekly incidence rates for a 4-week period of new episodes of infectious intestinal disease (IID) and laboratory reports of faecal isolations in children under 5 y of age presenting in general practice were used to estimate the incidence of IID due to rotavirus infection in England and Wales. Between January 1992 and December 1996, a total of 92452 new episodes of IID were seen at sentinel general practices and reported to the Royal College of General Practitioners (RCGP) Research Unit in Birmingham, UK. Of these 32% (29592) were in children under 5 y of age. During the same period the Communicable Disease Surveillance Centre (CDSC) in London, UK received 159532 reports of faecal identifications in children under 5 y of age; 69219 (43%) of these were due to rotavirus. By modelling RCGP data and laboratory reports, the proportion of episodes attributable to rotavirus infection was estimated to be 29% (95% CI: 24% to 34%). By extrapolation of RCGP data it was estimated that rotavirus accounted for 762000 of new episodes of IID nationally in children under 5 y of age between January 1992 and December 1996. Implementation of a rotavirus vaccination programme could substantially reduce the incidence of childhood diarrhoea.

Child, Preschool↗
PubMed1999

Prediction of perinatal outcome in fetuses suspected to have intrauterine growth restriction: Doppler US study of fetal cerebral, renal, and umbilical arteries.

PURPOSE: To determine and compare the diagnostic performance of fetal middle cerebral (MCA), renal (RA), and umbilical (UA) arterial Doppler ultrasonography (US) for prediction of adverse perinatal outcome in suspected intrauterine growth restriction (IUGR). MATERIALS AND METHODS: Two hundred ninety-three small-for-gestational age fetuses (24-39 weeks at recruitment and US-estimated weight or abdominal circumference below 10th percentile) were prospectively examined with Doppler US of the UA, MCA, and RA. Clinicians were blinded to MCA and RA Doppler measurements. RESULTS: Seventy-six fetuses (25.9%) had at least one major or minor adverse perinatal outcome. Major outcomes included stillbirth, neonatal death, neurologic complication, and necrotizing enterocolitis. The MCA pulsatility index (PI), compared with the UA PI and RA PI, was more sensitive (72.4% vs 44.7% and 8.3%) but less specific (58.1% vs 86.6% and 92.6%) in predicting adverse outcome. The UA PI had the highest positive likelihood ratio (ratio, 3.3); the MCA PI had the lowest negative likelihood ratio (ratio, 0.48). When gestational age at the first Doppler US examination was less than 32 weeks, the MCA PI had a sensitivity of 95.5% and negative predictive value of 97.7% for major adverse outcome (negative likelihood ratio, 0.10). CONCLUSION: In suspected IUGR, while an abnormal UA PI is a better predictor of adverse perinatal outcome than an abnormal MCA or RA PI, a normal MCA PI may help to identify fetuses without major adverse perinatal outcome, especially before 32 weeks gestational age.

Brain↗
PubMed1999

Recent advances in the methods of cost-benefit analysis in healthcare. Matching the art to the science.

This paper outlines recent advances in the methods of cost-benefit analysis (CBA). Economic evaluations in healthcare can be criticised for, amongst other things, the inappropriate use of incremental cost-effectiveness ratios and the reporting of benefits in terms of cost savings, such as treatment costs averted. Many such economic evaluations are, according to the 'scientific' definition, CBAs. The 'balance-sheet' (or opportunity cost) approach is a form of CBA which can be used to identify who bears the costs and who reaps the benefits from any change. Whilst the next stage in a CBA, as defined in health economics, would require that all costs and benefits be valued in monetary terms, the balance-sheet approach, however, advocates that available monetary values can be augmented by other measures of cost and benefit. As such, this approach, which has a theoretical basis, is proposed as a practical prescription for CBA and highlights the notion that unquantified benefits are important and can be included within CBAs even when monetarisation is not possible. Recent methodological developments in monetary valuation for use in CBA are the development of the technique of willingness to pay, the use of conjoint analysis (CA) to elicit willingness-to-pay (WTP) values and advances in the debate on the inclusion of production gains in CBAs. Whilst acknowledging that there have been developments in each of these areas, it is claimed there has also been progress in using CBA as a framework for evaluation, as reflected by the balance-sheet approach. The paper concludes by stating that almost all types of economic evaluation have an element of the 'cost-benefit' approach in them. The important issue is to focus on the policy question to be addressed and to outline the relevant costs and benefits in a manner which assists the evaluation of welfare changes resulting from changes in healthcare delivery. The focus should not be on moulding a question to fit a hybrid definition of an analytical technique.

Cost-Benefit Analysis↗
PubMed1999

Evaluation of traditional classroom teaching methods versus course delivery via the World Wide Web.

Higher education is moving with deliberate speed to an electronic classroom. Much has been published on faculty experiences with World Wide Web (WWW) course delivery. However, little research exists on the evaluation of these methods. The purpose of this study was to evaluate students' perceptions of two approaches to teaching: classroom and WWW modules. Classroom methods were rated significantly higher in relation to content, interaction, participation, faculty preparation, and communication. Technical skills were rated higher for WWW modules. Critical thinking and time allotted for assignments were not significantly different between classroom and WWW instruction. Open-ended comments were rich and supported both positive and negative aspects of classroom and WWW-based modules. Implications call for creativity in course development, course redesign and orientation, active communication with students, support for technical problems, faculty development, and university-wide planning through partnerships.

Attitude of Health Personnel↗
PubMed1999

Stress response decreases the interleukin-1beta-induced production of complement component C3 in human intestinal epithelial cells.

Interleukin-1beta (IL-1beta) increases the production of complement component C3 in enterocytes. Heat shock regulates the response to cytokines and other inflammatory mediators in various cell types. We tested the hypothesis that the heat-shock response regulates IL-1beta-induced C3 production in the enterocyte. Cultured Caco-2 cells, a human intestinal epithelial cell line, were treated with sodium arsenite (10-500 microM) for 1 h or subjected to hyperthermia (43 degrees C) for 1-4 h, and allowed to recover for 1 h. The cells were then treated with IL-1beta (0.5 ng/ml) for up to 24 h, whereafter C3 levels were measured by ELISA and C3 mRNA by Northern blot analysis. Heat-shock protein of 72 kDa (hsp72) was determined by Western blot analysis. Treatment of the cells with sodium arsenite or subjecting them to hyperthermia induced the expression of hsp72. The IL-1beta-induced expression of C3 mRNA and C3 production were down-regulated by hyperthermia and sodium arsenite in a dose-dependent fashion. The results suggest that the stress response induced by hyperthermia or sodium arsenite decreases IL-1beta-induced C3 production in human enterocytes.

Arsenites↗
PubMed1999

Regulation of follicle waves to maximize fertility in cattle.

Cattle have recurrent follicular waves every 7-10 days in most physiological situations; an FSH increase is associated with emergence of the wave and LH pulse frequency determines the fate of the dominant follicle. To control oestrus with hormones it is necessary to ensure that either induced corpus luteum regression or the termination of a progestogen treatment coincides with the selection of the dominant follicle during the wave, to give a precise onset of oestrus and high fertility. The exogenous administration of progesterone or progestagen blocks the normal turnover of the dominant follicle once the corpus luteum regresses. Thus, the effects of duration of dominance of the preovulatory follicle on onset of oestrus and fertility were examined. The variation in onset of oestrus was reduced but occurred 5-9 h later after 4 versus 8 days of dominance; pregnancy rate was also affected with dominance periods of 2-4, 4-8 and > 10 days resulting in 0, 10-15% or 20-50% reduction in pregnancy rates, respectively. The necessity for short duration of dominance of the preovulatory follicle means that to ensure high fertility the follicular wave needs to be regulated when using hormones to control oestrus. Two approaches were examined, namely the use of GnRH or oestradiol at time of progesterone intravaginal releasing device insertion. The effect of 250 micrograms of synthetic GnRH on the fate of an existing follicle wave was to ovulate the dominant follicle (20/20 cows) and a new wave emerged 1.6 +/- 0.3 days later; however, there was no effect of GnRH on the wave if administered before dominant follicle selection. The effect of oestradiol concentrations on suppression of FSH in ovariectomized heifers showed that increasing oestradiol to 10-15 pg ml-1 caused a 37 +/- 6.9% decrease in FSH for 24 h, with a subsequent increase to pretreatment values by 57 +/- 13 h. In cyclic heifers, increasing oestradiol to > 10 pg ml-1 in conjunction with progesterone treatment at emergence of the first wave of the cycle affected the current follicle wave by either preventing dominant follicle selection or decreasing diameter of the dominant follicle, without consistently affecting the interval to new wave emergence. Increase of oestradiol after dominance, however, delayed new wave emergence by 2-5 days. A better understanding of the hormonal control of follicle waves will lead to development of improved hormonal regimens to control oestrus sufficiently to give high pregnancy rates to a single AI without recourse to detection of oestrus.

Animals↗
PubMed1999

A role for conjoint analysis in technology assessment in health care?

The aim of this paper is to demonstrate the use of conjoint analysis (CA) in health services research. Conjoint analysis is first explained, with emphasis on the history of the technique, followed by an explanation of how to carry out such a study and how the results from such a study can be used. The technique is demonstrated with reference to a study that looks at the benefits of in vitro fertilization. It is shown how CA can be used to estimate the relative importance of attributes, the trade-offs individuals make between these attributes, willingness to pay if cost is included as an attribute, and utility or benefit scores for different ways of providing a service. The paper then considers the potential advantages of CA over other, more commonly used benefit assessment instruments. Finally, there is discussion of the issues raised in the design and analysis of CA studies. It is concluded that these issues must be addressed before the technique becomes an established instrument for technology assessment.

Adult↗
PubMed1998

Use of a broad-host-range bacteriocin-producing Lactococcus lactis transconjugant as an alternative starter for salami manufacture.

Lactococcus lactis DPC4268 is widely used for Cheddar cheese manufacture in Ireland where it is recognised for its reliable fast acid producing ability in dairy environments. A transconjugant of this strain, L. lactis DPC4275, was generated which produces the broad spectrum, two-component bacteriocin lacticin 3147, which is inhibitory to a variety of undesirable gram-positive bacteria including Clostridium, Bacillus, Enterococcus, Listeria, Staphylococcus and Streptococcus. Both DPC4268 and DPC4275 were used as single strain starters for manufacture of salamis. These products were compared with a salami manufactured with a conventional starter (Lactobacillus sake and Staphylococcus carnosus) in terms of pH development, a(w)-value, weight loss, colour development and sensory characteristics. Salamis produced with either lactococcal culture exhibited pH values below 5.1 and a(w)-values below 0.90 which is favourable for preservation and hygienic stability. In addition, these salamis had good sensory and colorimetric qualities. A minimum lacticin 3147 concentration of 640 AU/g was detected in the salamis which were produced with L. lactis DPC4275.

Animals↗
PubMed1998

The pharmacokinetics of combination therapy with nelfinavir plus nevirapine.

OBJECTIVE: To investigate the pharmacokinetics of nelfinavir (NFV) administered alone and in combination with nevirapine (NVP) to HIV-positive patients. DESIGN: Seven patients with advanced HIV disease received dual nucleoside analogues in addition to NFV (750 mg three times daily) and subsequently NVP (200 mg daily for 2 weeks followed by 200 mg twice daily) as salvage therapy. On the first study day (day 3), blood samples were taken for assay of NFV. The second study day followed the introduction of NVP for 3 weeks. METHODS: Blood samples were obtained at 0, 1, 2, 3, 4, 6 and 8 h after dosing on both study days. Separated plasma was heated to 58 degrees C for 30 min to inactivate HIV and stored at -80 degrees C until analysis by high performance liquid chromatography for both NFV and NVP. RESULTS: The geometric mean NFV area under the concentration-time curve to 8 h (AUC0-8h) was 23.4 microg x h/ml (range, 13.5-49.2) and 11.6 microg x h/ml (range, 6.6-23.2) on the first and second study days, respectively. The geometric mean ratio was 0.49 (95% confidence interval, 0.33-0.72; P = 0.016). This represented a 50% reduction in plasma NFV concentrations. Maximum and minimum concentrations were also reduced during NVP therapy (from 4.4 to 2.5 microg/ml and from 1.7 to 0.8 microg/ml, respectively). Time to maximum concentration was reduced from 4 to 2 h. NVP concentrations were determined with a maximum concentration of 5.4 microg/ml at 4 h. CONCLUSIONS: NVP is currently being used in combination therapy with protease inhibitors for antiretroviral-experienced patients in the setting of treatment failure. This study demonstrates that when patients are coadministered NVP there is a 50% reduction in the plasma AUC of NFV. Although the mean trough concentrations of NFV remained above the stated minimum effective concentration of 0.4 microg/ml, there is nevertheless concern that some patients will fall below this value when NVP is added to treatment regimens. In the absence of therapeutic drug monitoring we suggest that an increase in the standard NFV dosage of 750 mg three times daily will be required to ensure satisfactory NFV plasma concentrations, thereby maintaining antiviral efficacy.

Adult↗
PubMed1998

Use of systematic reviews of randomised trials by Australian neonatologists and obstetricians.

OBJECTIVE: To determine what proportion of Australian neonatologists and obstetricians report using systematic reviews of randomised trials. DESIGN: Cross-sectional survey using structured telephone interviews. SETTING: Australian clinical practice in 1995. PARTICIPANTS: 103 of the 104 neonatologists in Australia (defined as clinicians holding a position in a neonatal intensive care unit); a random sample of 145 members of the Royal Australian College of Obstetricians and Gynaecologists currently practising in Australia. MAIN OUTCOME MEASURES: Information sources used in clinical practice; reported awareness of, access to and use of systematic reviews, and consequent practice changes. RESULTS: Response rates were 95% (neonatologists) and 87% (obstetricians); 71 neonatologists (72%) and 55 obstetricians (44%) reported using systematic reviews, primarily for individual patient care. Databases of systematic reviews were used with a median frequency of once per month. Among neonatologists, systematic reviews were used more commonly by those who were familiar with computers, attended professional meetings, and had authored research papers. Among obstetricians, they were used more commonly by those who were familiar with computers, had less than 10 years' clinical experience, attended more deliveries, and were full-time staff specialists in public hospitals. Of neonatologists who reported using systematic reviews, 58% attributed some practice change to this use. For obstetricians, the corresponding figure was 80%. CONCLUSIONS: There is evidence that Australian neonatologists and obstetricians use systematic reviews and modify their practice accordingly. Dissemination efforts can benefit from knowledge of factors that predict use of systematic reviews.

Adult↗
PubMed1998

Atrial natriuretic peptide increases urinary albumin excretion in men with type 1 diabetes mellitus and established microalbuminuria.

Raised plasma concentrations of atrial natriuretic peptide (ANP) have been reported in patients with Type 1 (insulin dependent) diabetes mellitus (DM) who have poor glycaemic control and are associated with the presence of microalbuminuria. To test the hypothesis that elevations in plasma ANP concentration increase urinary albumin excretion in Type 1 DM, we have studied the effects of intravenous infusions of ANP in eight such subjects with established microalbuminuria. Blood glucose was maintained between 4 and 7 mmol l-1 in all subjects for the duration of studies; after euglycaemia had been established, a standard oral water load (20 ml kg-1 plus replacement of urinary losses) was given. Once steady state diuresis was attained, subjects received intravenous infusion of either placebo (0.9% saline), low dose (2.5 pmol kg-1 min-1) or high dose (5.0 pmol kg-1 kg min-1) ANP solution in a randomized, double-blind protocol. Infusion of ANP caused a dose-dependent increase in urinary albumin excretion rate (placebo, 11.3 (SD 8.9) to 8.7 (SD 6.8) micrograms min-1; low dose ANP, 12.4 (SD 9.9) to 26.5 (SD 27.5) micrograms min-1, p < 0.01; high dose ANP 10.3 (SD 7.3) to 36.6 (SD 28.5) micrograms min-1, p < 0.001, ANOVA). Only high dose ANP caused an increase in urine flow. Blood glucose remained unchanged in all studies. We conclude that intravenous infusions of ANP cause a dose-dependent increase in urinary albumin excretion rate in Type 1 DM subjects with microalbuminuria. These data support the hypothesis that ANP has albuminuric actions which may contribute to microalbuminuria in Type 1 DM.

Adult↗
PubMed1998

Methodological issues in the application of conjoint analysis in health care.

This paper adds to an increasing literature on methodological questions addressed in the application of conjoint analysis (CA) in health care. Three issues are addressed: ordering effects; internal validity; and internal consistency. The results of an application of CA in a primary care setting provide no evidence that the ordering of scenarios was important. Evidence was found of both internal validity and internal consistency. In addition, individual preferences were found to be determined by experiences, which raise potentially important questions regarding the elicitation and use of such preferences in economic evaluation.

Appointments and Schedules↗