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Biomedical subjects

M Ryan

Publications and source records attributed to M Ryan.

At least 37 records · Page 2Linked to original sources

Effect of insulin treatment on the body composition of Type 2 diabetic patients.

OBJECTIVE: Insulin is used commonly in Type 2 diabetes and is often accompanied by weight gain. The composition of this weight gain is poorly understood. Predominant increases in fat mass could increase cardiovascular risks. The aim of the study was to evaluate insulin-induced body composition changes. RESEARCH DESIGN AND METHODS: Body weight and composition of 35 Type 2 diabetic patients during their first 6 months of insulin therapy was compared with those in 34 Type 2 diabetic individuals treated with insulin for at least 1 year prior to commencing the study. Body composition was determined by the simultaneous measurement of body water spaces and body density. RESULTS: Over 6 months, glycaemic control improved in the new treatment group only (HbA(1c): 7.26 +/- 0.81 vs. 9.66 +/- 1.60%; P < 0.0001), remaining stable in the previously treated group (7.67 +/- 1.25 vs. 7.76 +/- 1.26%; P = NS). Weight significantly increased over time in the newly treated group (+1.7 kg; P = 0.04), but not in the previously treated group (-0.3 kg). It comprised of both fat (+0.85 kg) and fat-free mass (+0.55 kg). Total body water remained unchanged. Using bioelectrical impedance analysis, the gain in fat mass was +2.2 kg; P = 0.048. CONCLUSIONS: Over 6 months, insulin therapy leads to a weight gain of 1.7 kg because of an increase in both fat and fat-free mass. When body composition is determined by bioelectrical impedance analysis, the results are biased by fluctuations in hydration.

Aged↗

The natural history of the periacetabular fragment following Ganz osteotomy.

The vascularity of the acetabular free fragment in Ganz osteotomies has remained a concern. This study aims to assess the role of MR imaging in the postoperative evaluation of Ganz osteotomies. Twenty patients (19 females, 1 male), average age 24 years (range, 12-36 years), had sequential magnetic resonance imaging studies of the pelvis at 6 weeks and 6 months following Ganz osteotomies. Normal healing with no evidence of periosteotomy edema was seen in 17 patients at 6 weeks. Three patients showed evidence of reduced vascularity. In two of these, there were focal changes suggestive of subclinical ischemia. The other had gross signal changes in the osteotomy fragment suggestive of diffuse ischemia. The patients with focal changes were asymptomatic and had normal 6-month scans. The patient with diffuse changes complained of persistent groin pain, which resolved after 4 months. The 6-month scan showed some persistent vascular changes. The scan at 1 year showed complete resolution. The study suggests that Ganz osteotomy has minimal effect on the vascularity of the acetabular free fragment.

Acetabulum↗

General practice management of illicit drug users in Scotland: a national survey.

AIMS: To describe the level of involvement of general practitioners (GPs) in the management of illicit drug dependency; nature of current practice in the management of illicit drug dependency; influence of guidelines on practice; GP training experience and needs; and to consider the policy implications of the findings. DESIGN: A cross-sectional postal questionnaire survey. SETTING: General practice in Scotland. PARTICIPANTS: A 1 : 4 randomized sample (n = 926) of general practice principals, stratified according to age, gender and number of practice partners. MEASUREMENTS: A structured postal questionnaire. FINDINGS: A 63% response rate was achieved after two reminders (n = 583). Sixty per cent of respondents treated drug users, 51.5% provided methadone maintenance but only 58% used doses in the recommended range. Maintenance prescribing of dihydrocodeine and benzodiazepines was provided by 24% and 44.8% of respondents, respectively. While 79.3% had received the national clinical guidelines only 22.5% believed this had influenced their practice. Only a third of respondents had received drug dependency training. Beliefs about whether prescribing for drug misusers is part of a GPs professional remit was split. CONCLUSIONS: There was relatively high involvement with drug users, with methadone maintenance being the most common treatment provided. Maintenance prescribing of dihydrocodeine and benzodiazepines were common despite a lack of clinical evidence supporting the effectiveness of these treatments. This may reflect the nature of the presenting drug problems and highlights the difficulties some GPs may face in managing multiple drug dependencies within current guidelines. Further local training to implement guidelines along with trials of alternative treatments currently outwith guidelines should be considered.

Adult↗

The value of routine MR myelography at MRI of the lumbar spine.

PURPOSE: To determine whether a commercially available automated MR myelogram sequence improves the interpretation and diagnostic yield at MRI of the lumbar spine. MATERIAL AND METHODS: A total of 207 consecutive patients referred for MR examination of the lumbar spine for evaluation of low back pain or spinal radicular symptoms were included for study. All patients had initial imaging with sagittal T1-W and T2-W scans, followed by axial T2-W images. Subsequently an MR myelogram was acquired in each case in coronal, sagittal and oblique planes. MR myelogram images were evaluated initially and a diagnosis was established and recorded. Subsequently, a diagnosis was established by review of conventional images of the lumbar spine in sagittal and axial planes, in conjunction with the MR myelogram. The utility of the MR myelogram in establishing the diagnosis was graded on a 4-point scale, where grade 0 indicated that it contributed no additional information and grade 3 indicated that it was essential for diagnosis. Analysis of the additional value of myelography in patients with multilevel disease was made. RESULTS: Primary diagnoses were disc herniation in 69 cases (33%), degenerative disc disease in 51 cases (26%), spinal stenosis in 19 cases (9%), isolated lateral recess stenosis in 5 cases (2%), or other diagnoses, including facet degeneration in 48 cases (23%). Scans were normal in 15 cases (7%). MR myelography was graded as grade 0 in 151 cases (73%), grade 1 in 44 cases (21%) and grade 2 in 12 cases (6%). In no case was MR myelography essential for diagnosis (grade 3). In patients with multilevel disease (n=27), in 17 cases MR myelography was graded as grade 1 (63%) and in 8 cases grade 2 (30%). CONCLUSION: MR myelography when employed in routine practice was of limited value, assisting in establishing a diagnosis in a minority of cases (6%). The technique was of limited additional value in patients with multilevel pathology and to a lesser extent in patients with scoliosis, where it helped to establish the level most likely to account for pathology.

Adolescent↗

Role of the sensitivity of detection of oestrus in the submission rate of cows treated to resynchronise oestrus.

OBJECTIVE: To determine if failure to detect oestrus in cows treated to resynchronise oestrus leads to fewer cows being inseminated than are truly in oestrus. PROCEDURE: Cows in three herds were enrolled in a controlled breeding program that involved synchronisation of oestrus for a first round of artificial insemination (AI) followed by resynchronisation for a second round of AI. Just before oestrus was expected at the second round of AI, aids for the detection of oestrus were fitted, which included pedometers, radiotelemetric transmitters (HeatWatch), tail-paint and heatmount detectors. Milk samples were collected at the second round of AI (day 33, herds A and B; day 35, herd C of the treatment program) and were used in combination with pregnancy testing to determine the number of cows that were in oestrus (milk progesterone < 2.0 ng/mL) and cows that were not in oestrus (milk progesterone > 2.0 ng/mL or pregnant at second round of AI) at the time samples were collected. RESULTS: The mean sensitivity of detection of oestrus at the resynchronised oestrus was 92.5% and did not differ significantly between herds (P = 0.19). A total of 75% (60/80) of cows that were retrospectively determined to be not pregnant at the time of the second round of AI were classified as having high (> or = 2.0 ng/mL) concentrations of progesterone in milk at that time. Pregnancy testing of cows about 35 days after AI suggested that early pregnancy loss also contributed to a reduction in submission rates at the resynchronised oestrus. CONCLUSION: Failure to submit cows for insemination at a resynchronised oestrus was mainly due to cows not being in oestrus rather than due to a failure to detect oestrus.

Animals↗

Comparison of four methods for detection of oestrus in dairy cows with resynchronised oestrous cycles.

OBJECTIVE: To compare the sensitivity and positive predictive value of four methods for detection of oestrus in dairy cows with resynchronised oestrous cycles. PROCEDURE: Oestrous cycles in cows in three herds were synchronised for a first round of artificial insemination (AI) and then resynchronised for a second round of AI. Sensitivity and positive predictive value of four aids (pedometers, radiotelemetric transmitters [HeatWatch; HW], tail-paint and heatmount detectors) that were used to detect the resynchronised oestrus were compared. Milk progesterone concentration and pregnancy testing at 12 weeks were used as the reference standard for cows being in oestrus. RESULTS: The mean sensitivity and positive predictive value for detecting the resynchronised oestrus, for each aid that was used, was > 80%. Tail-paint was significantly more sensitive at detecting oestrus compared to heatmount detectors (P = 0.002), but not significantly more sensitive than pedometers (P = 0.07) or HW (P = 0.55) for detecting oestrus (91.3, 85.7; 81.4 and 88.4%, respectively). Positive predictive value of HW for detecting oestrus was greater than tail-paint (P = 0.014) and heatmount detectors (P = 0.024) but not pedometers (P = 0.25; 100, 91.7, 92.9 and 87.5%, respectively). Positive predictive value of heatmount detectors was greater than pedometers in herd C (93.4% vs 73.3%; P = 0.035) but not in herds A (95.0% vs 90.0%; P = 0.56) or B (90.8% vs 100%; P = 0.10). No other significant differences in sensitivity or positive predictive value of detection of oestrus were found between aids. CONCLUSION: Tail-paint, heatmount detectors, pedometers and HW provide a high sensitivity (> 80%) and positive predictive value (> 85%) of detecting oestrus in dairy cows with resynchronized oestrous cycles.

Animals↗

Use of the infant transwarmer mattress as an external warming modality in resuscitation from hypothermia.

Normothermia must be established in drowning victims before death may be declared, as the myocardium may remain resistant to stimulation at subnormal temperatures, and complete neurological recovery from submersion associated hypothermia has been reported. A safe and effective method of external re-warming is described that may prove particularly useful in the paediatric population.

Beds↗

Generic drug utilisation on the General Medical Services (GMS) scheme in 2001.

Expenditure on medicines under the Community Drug Schemes was Euro 674.8 million in 2001, a 27% increase as compared with the year 2000. Prescribing less expensive generic drugs is one method of reducing costs whilst maintaining therapeutic efficacy. In this study the cost and quantity of generic drugs dispensed and the potential savings for GMS prescribing in 2001 that could be made by increasing utilisation of generic drugs was investigated. Twenty two per cent of prescription items were dispensed generically (branded generics (17%) and non-branded generics (5%)) in 2001. This represented approximately 13% of the total ingredient cost of drugs dispensed in that period. Eighteen per cent of prescription items were dispensed as proprietary preparations when a generic equivalent was available. Eleven of the top 30 drugs, of highest cost to the GMS scheme, had a generic equivalent which if substituted could produce savings in the region of Euro 5.65 million. The results of this study highlight the potential for cost savings to be made by generic substitution, facilitating the most efficient use of the limited drugs budget.

Drug Prescriptions↗

Cost of treating stroke in an Irish teaching hospital.

In contrast to CHD and cancer, the burden of stroke lies with long term disability as opposed to death and it is the most common cause of neurological disability in the western world. Consequently such patients frequently require longer acute hospital stays followed by lengthy periods of rehabilitation where such services are available, long term nursing care or indefinite dependency on community care. Inevitably stroke is a major economic burden on healthcare systems. It has been estimated that approximately 6% of total healthcare resources are consumed in the management of this condition a figure which is expected to grow with an increasing elderly population. Due to the high level of disability caused by stroke, patients often require longer and therefore costly periods of acute hospital stay. The aim of this study is to determine the cost of treating an acute episode of ischaemic stroke in an Irish teaching hospital. The costing evaluation was from the hospital admission perspective and the strategy used was a microcosting detailed collection of resources used on patients admitted to St. James's hospital between January 1999 and March 2000. The average cost of a hospital admission for the treatment of an episode of acute ischaemic stroke was 6,722 euros. The average cost per day was calculated at 263 euros. Approximately 83% of hospital costs were associated with ward costs whereas medications accounted for just 1% of total costs. The projected cost for the treatment of stroke in euros using the consumer price index for October 2002 would be 7,686 euros. The availability of Irish cost data is essential for the assessment of the cost effectiveness of therapeutic interventions for the treatment of stroke in our healthcare system.

Aged↗

Decision-making by healthcare payers.

Healthcare payers are faced with the need to allocate finite resources to maximize population health. To assist in decision-making, healthcare payers are increasingly using health outcomes information and economic analyses. Healthcare payers are often under pressure to make early decisions (around the time of product launch), when the evidence available is imperfect. They must also consider the equitable distribution of resources between therapeutic areas. Tools to help healthcare payers reach transparent and objective decisions include cost-utility analysis and decision modelling. In practice, healthcare payers in different countries (for example, Ireland, France and Canada) vary in the approaches taken to reimbursement and formulary listing decisions. The key to decision-making among healthcare payers is the provision of appropriate evidence, comparing any new treatment approach to current best practice, in situations corresponding to real life. When data assumptions have to be made, these should be clearly stated with consideration of the impact of varying the assumptions. The impact on budgets should also be considered.

Attitude of Health Personnel↗

Aging and accumulation of microdamage in canine bone.

Fractures associated with minimal trauma are common in aged human beings. However, bone safety margins are better preserved in aged dogs, which are rarely affected with minimal trauma fractures. Although the hierarchical architecture of canine and human compact bone is similar, the precise reasons for this species difference are unclear. Cyclic loading of bone during normal daily activity leads to the formation of microcracks within the tissue matrix of compact bone. Using a standard bulk-staining technique with basic fuchsin, we examined calcified transverse sections of the mid-diaphysis of the canine humerus from dogs of varying ages. We found that the amount of microdamage and porosity increased exponentially with aging, although the increases were relatively small, compared with human bone. Gender (female, ovariohysterectomized female, male, castrated male) did not have a significant effect on the amount of microdamage or porosity in bone. Alterations to the local material properties of bone tissue, or alterations to the local tissue repair responses, may play a role in the accumulation of microdamage in bone with aging. Determination of osteocyte lacunar density (number of osteocyte lacunae per bone area) and activation frequency (number of actively remodeling osteons per bone area per year) indicated that these variables declined exponentially with aging. There also was a trend for bone from dogs with low osteocyte lacunar density to have a higher microcrack density, but not higher porosity. Furthermore, bones with a high activation frequency did not accumulate microcracks or porosity. Taken together, these data suggest that, in canine bone, although a certain minimum number of osteocytes may be essential for an operational network that forms part of the signaling pathways that orchestrate repair of bone microdamage, increases in porosity with aging may not be directly associated with impaired function of the osteocyte network within bone.

Aging↗

The use of local accident and emergency injury surveillance to monitor the impact of a lay safety community programme.

To study prospectively the injury patterns in under 14 year olds presenting to casualty. To use this information to assess the impact of a local Community Childhood Accident Prevention Project (CCAPP) Prospective injury surveillance was collected on all attendees under 14 years of age. Casualty attendance for the members of the Safety Club and matched controls were analysed. Of the 4,267 attendees there was the expected male predominance. 2,261 (53%) of injuries occurred at home, 574 (13.5%) on the road, 553 (13%) at school with 202 (4.7%) during sports. Priority areas noted were high falls > 1 metre, road accidents, burns and poisonings. Those participating in the program demonstrated significantly (p-value < 0.05) reduced admission rates and head injury rates when compared to non-participants. The above database allows us to analyse injury patterns and to assess the success of an EU-sponsored local injury prevention campaign in areas of high social deprivation.

Accident Prevention↗

Data analyst technician: an innovative role for the pharmacy technician.

The development of an innovative role for the pharmacy technician is described. The role of the pharmacy technician was based on a needs assessment and the expertise of the pharmacy technician selected. Initial responsibilities of the technician included chart reviews, benchmarking surveys, monthly financial impact analysis, initiative assessment, and quality improvement reporting. As the drug-use and disease-state management (DUDSM) program expanded, pharmacist activities increased, requiring the expansion of data analyst technician (DAT) duties. These new responsibilities included participation in patient assessment, data collection and interpretation, and formulary enforcement. Most recently, technicians' expanded duties include maintenance of a physician compliance profiling database, quality improvement reporting and graphing, active role in patient risk assessment and database management for adult vaccination, and support of financial impact monitoring for other institutions within the health system. This pharmacist-technician collaboration resulted a threefold increase in patient assessments completed per day. In addition, as the DUDSM program continues to expand across the health system, an increase in DAT resources from 0.5 to 1.0 full-time equivalent was obtained. The role of the DAT has increased the efficiency of the DUDSM program and has provided an innovative role for the pharmacy technician.

Academic Medical Centers↗

Hyponatremia and leukopenia associated with oxcarbazepine following carbamazepine therapy.

Straightforward reports of unusual drug experiences are included in this section. While selected references may be cited, the purpose of a Drug Experience report is not to present an extensive review of the literature. A related section, Grand Rounds, includes papers that are well-documented patient case reports with a thorough review of the important literature to help put the case in perspective. Authors should report serious adverse drug reactions to the FDA medical products reporting program (MedWatch). Such reporting will not jeopardize the chances that AJHP will publish manuscripts on the same drug reactions.

Anticonvulsants↗

A catalytic diad involved in substrate-assisted catalysis: NMR study of hydrogen bonding and dynamics at the active site of phosphatidylinositol-specific phospholipase C.

Phosphatidylinositol-specific phospholipase Cs (PI-PLCs, EC 3.1.4.10) are ubiquitous enzymes that cleave phosphatidylinositol or phosphorylated derivatives, generating second messengers in eukaryotic cells. A catalytic diad at the active site of Bacillus cereus PI-PLC composed of aspartate-274 and histidine-32 was postulated from the crystal structure to form a catalytic triad with the 2-OH group of the substrate [Heinz, D. W., et al. (1995) EMBO J. 14, 3855-3863]. This catalytic diad has been observed directly by proton NMR. The single low-field line in the 1H NMR spectrum is assigned by site-directed mutagenesis: The peak is present in the wild type but absent in the mutants H32A and D274A, and arises from the histidine Hdelta1 forming the Asp274-His32 hydrogen bond. This hydrogen is solvent-accessible, and exchanges slowly with H2O on the NMR time scale. The position of the low-field peak shifts from 16.3 to 13.8 ppm as the pH is varied from 4 to 9, reflecting a pKa of 8.0 at 6 degrees C, which is identified with the pKa of His32. The Hdelta1 signal is modulated by rapid exchange of the Hepsilon2 with the solvent. Estimates of the exchange rate as a function of pH and protection factors are derived from a line shape analysis. The NMR behavior is remarkably similar to that of the serine proteases. The postulated function of the Asp274-His32 diad is to hydrogen-bond with the 2-OH of phosphatidylinositol (PI) substrate to form a catalytic triad analogous to Asp-His-Ser of serine proteases. This is an example of substrate-assisted catalysis where the substrate provides the catalytic nucleophile of the triad. This hydrogen bond becomes shorter as the imidazole is protonated, suggesting it is stronger in the transition state, contributing further to the catalytic efficiency. The hydrogen bond fits the NMR criteria for a short, strong hydrogen bond, i.e., a highly deshielded proton resonance, bond length of 2.64 +/- 0.04 A at pH 6 measured by NMR, a D/H fractionation factor significantly lower than 1.0, and a protection factor > or = 100.

Bacillus cereus↗

Chemokine receptor CCR4 on CD4+ T cells in juvenile rheumatoid arthritis synovial fluid defines a subset of cells with increased IL-4:IFN-gamma mRNA ratios.

To understand the mechanisms that promote recruitment and survival of T cells within the pediatric inflamed joint, we have studied the expression of CCR4 and CCR5 on synovial fluid T cells and matched peripheral blood samples from juvenile rheumatoid arthritis (JRA) patients using three-color flow cytometric analysis. Thymus- and activation-regulated chemokine and macrophage-derived chemokine, ligands for CCR4, were measured by ELISA in JRA synovial fluid, JRA plasma, adult rheumatoid arthritis synovial fluid, and normal plasma. IL-4 and IFN-gamma mRNA production was assessed in CD4+/CCR4+ and CD4+/CCR4(-) cell subsets. We found accumulations of both CCR4+ and CCR5+ T cells in JRA synovial fluids and a correlation for increased numbers of CCR4+ T cells in samples collected early in the disease process. Thymus- and activation-regulated chemokine was detected in JRA synovial fluid and plasma samples, but not in adult rheumatoid arthritis synovial fluid or control plasma. Macrophage-derived chemokine was present in all samples. CD4+/CCR4+ synovial lymphocytes produced more IL-4 and less IFN-gamma than CD4+/CCR4(-) cells. These findings suggest that CCR4+ T cells in the JRA joint may function early in disease in an anti-inflammatory capacity through the production of type 2 cytokines and may play a role in determining disease phenotype.

Adolescent↗