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Biomedical subjects

A Kelly

Publications and source records attributed to A Kelly.

At least 73 records · Page 4Linked to original sources

Growth in use of statins after trials is not targeted to most appropriate patients.

OBJECTIVE: To determine whether growth in the use of lipid-lowering drugs after publication of studies in the primary and secondary prevention of coronary heart disease is in the population in which benefit was established, particularly middle-aged men. METHODS: We performed a series of pharmacoepidemiologic surveys of community prescribing in Ireland over 4 years. RESULTS: Nationally, the use of lipid-lowering drugs (92% statins) increased approximately fourfold from 1994 to 1998. In the Eastern Health Board region, the number of monthly recipients increased from 447 in April 1994 to 3530 in March 1998. Although use increased steadily after publication of Scandinavian Simvastatin Survival Study (4S) and West of Scotland Coronary Prevention Study (WOSCOPS) in 1994 and 1995, respectively, this occurred to a greater extent in women. However, after the Cholesterol and Recurrent Events (CARE) study in 1996 and subsequent recommendations that targeted statin use, particularly in men from 35 to 69 years old, there was a relatively greater increase in that population but, at 2.3%, it was well short of the target population of 5.8%. More women than men older than 65 years are receiving statins. The 10-mg dosage (a fourth or half that used in studies) is the most frequently dispensed. CONCLUSION: The use of statins, although rising rapidly, is below targets and was initially not directed at the population likely to benefit most or in the recommended dosage. Consequently, the benefits projected from clinical trials may not be seen in clinical practice.

Adult↗

Calcium-stimulated insulin secretion in diffuse and focal forms of congenital hyperinsulinism.

OBJECTIVES: To identify infants with hyperinsulinism caused by defects of the beta-cell adenosine triphosphate-dependent potassium channel complex and to distinguish focal and diffuse forms of hyperinsulinism caused by these mutations. STUDY DESIGN: The acute insulin response to intravenous calcium stimulation (CaAIR) was determined in 9 patients <20 years with diffuse hyperinsulinism caused by defective beta-cell sulfonylurea receptor (SUR1(-/-)), 3 patients with focal congenital hyperinsulinism (6 weeks to 18 months), a 10-year-old with insulinoma, 5 with hyperinsulinism/hyperammonemia syndrome caused by defective glutamate dehydrogenase (6 months to 28 years), 4 SUR1(+/-) heterozygotes with no symptoms, and 9 normal adults. Three infants with congenital focal disease, 1 with diffuse hyperinsulinism, and the child with insulinoma underwent selective pancreatic intra-arterial calcium stimulation with hepatic venous sampling. RESULTS: Children with diffuse SUR1(-/-) disease and infants with congenital focal hyperinsulinism responded to CaAIR, whereas the normal control group, patients with hyperinsulinism/hyperammonemia syndrome, and SUR1(+/-) carriers did not. Selective arterial calcium stimulation of the pancreas with hepatic venous sampling revealed selective, significant step-ups in insulin secretion that correlated anatomically with the location of solitary lesions confirmed surgically in 2 of 3 infants with congenital focal disease and in the child with insulinoma. Selective arterial calcium stimulation of the pancreas with hepatic venous sampling demonstrated markedly elevated baseline insulin levels throughout the pancreas of the infant with diffuse hyperinsulinism. CONCLUSIONS: The intravenous CaAIR is a safe and simple test for identifying infants with diffuse SUR1(-/-) hyperinsulinism or with focal congenital hyperinsulinism. Preoperative selective arterial calcium stimulation of the pancreas with hepatic venous sampling can localize focal lesions causing hyperinsulinism in children. The combination of these calcium stimulation tests may help distinguish focal lesions suitable for cure by local surgical resection.

ATP-Binding Cassette Transporters↗

Do patient age and medical condition influence medical advice to stop smoking?

OBJECTIVE: to determine whether the age and medical condition of a patient influences hospital-based doctors' decision making when advising patients to stop smoking cigarettes. METHODS: we presented 142 doctors from four grades (consultant, registrar, senior house officer and house officer) and four specialities (medicine, surgery, psychiatry and anaesthetics), based in a Dublin teaching hospital, with 20 clinical vignettes. Each vignette described a patient from one of five age groups with one of four levels of health. The vignettes were randomly mixed. We asked doctors to say whether they would advise the patient in each case to quit smoking. RESULTS: hospital-based doctors are significantly less likely to advise patients aged over 65 years than younger patients of the hazards of cigarette smoking, irrespective of the person's physical or mental health (P < 0.001). CONCLUSION: the advice given to patients about their cigarette smoking habits by hospital doctors is strongly influenced not only by the patient's health, but also by the patient's chronological age.

Age Factors↗

Acupressure and prevention of nausea and vomiting during and after spinal anaesthesia for caesarean section.

The efficacy of acupressure at the P6 point in the prevention of nausea and vomiting during and after Caesarean section was studied. A double-blind, randomized controlled study of acupressure vs placebo was designed. Ninety-four patients scheduled for Caesarean section were included. The anaesthetic technique and postoperative analgesia were standardized. The use of acupressure reduced the incidence of nausea or vomiting from 53% to 23% compared with placebo (95% confidence interval (CI) 0.34-0.25; P = 0.002) during the operation and from 66% to 36% compared with placebo (95% CI 0.34-0.19; P = 0.003) after the operation. Other variables were similar between the groups.

Acupressure↗

Assessment of health status at two years of very low birthweight infants--clinical governance.

Aims to establish a mechanism to determine prospectively the health status at two years of babies who weighed less than 1.5 kg at birth, born and receiving neonatal intensive care in North Wales. Maternal and neonatal data on all babies discharged from each of the three units in North Wales meeting this criteria were collated by the study coordinator. A mechanism for review of the health status at two years, corrected for gestational age, was established using the data set recommended by a working group convened by the National Perinatal Epidemiology Unit and Oxford Regional Health Authority. The procedures developed and the outcome data, for a two year cohort of babies born in 1995 and 1996, are reported. Concludes that prevalence of severe disability was similar to that found in other studies, with a considerable number exhibiting impaired growth and delay in speech development.

Child Development↗

Fracture of the occipital condyle: the forgotten part of the neck.

A case of occipital condylar fracture in a multiply injured and unconscious motorcyclist is reported. This injury was clinically unsuspected but found on the lowest cuts of head computed tomography. It is shown that this site is often inadequately imaged when scanning the head and neck in victims of trauma. The Anderson and Montesano classification of occipital condylar fracture is described. It is noted that types 1 and 2 are stable injuries but type 3 is potentially unstable. A retrospective analysis of 30 head computed tomography scans in trauma cases revealed that in only 16 were the occipital condyles adequately imaged. It is emphasised that vigilance is required to detect fractures of the occipital condyle and that it should be standard practice to include this area when performing computed tomography of the head in trauma victims.

Adolescent↗

Differences in circulating concentrations of total, free and bound leptin relate to gender and body composition in adult humans.

We describe a radioimmunoassay (RIA) for total leptin and a gel filtration procedure for the separation of free and bound leptin in human serum. The RIA, based on a locally prepared antibody, has a minimum detection limit of 0.9 ng/mL, a working range (CV < 10%) of 2.5-50 ng/mL, inter-assay precision of 10.2, 7.2 and 8.9%CV at 7.9, 15.4 and 30.0 ng/mL, respectively, 94% recovery of exogenous leptin (range 81.1-120.6%), exhibited parallelism and demonstrated no significant cross-reactivity or interferences. A difference plot of results from this method and those from a commercially available kit (Linco Research) demonstrated satisfactory agreement up to concentrations of 50 ng/mL total leptin, with no significant bias. A gender-dependent correlation was obtained between body mass index (BMI) and total leptin (r = 0.91, P<0.001, n = 75 for men; r = 0.79, P<0.001, n = 72 for women), with women having higher leptin concentrations than men for any given BMI. Gel filtration studies (inter-assay precision: 4.7%CV, n = 18) demonstrated that a variable fraction (between 10% and 40%) of total leptin in serum was bound with high affinity (Keq = 1.0-1.45 x 10(9) L/mol) to a non-albumin, non-lipid macromolecule. Binding affinities were found to be similar irrespective of gender or fat mass. A significant positive correlation between free or bound leptin concentrations and BMI was obtained for both men and women (r = 0.87-0.94); free and bound leptin concentrations were also significantly higher in women (P<0.01) than in men for any given BMI, and higher in obese (P<0.01) than in lean individuals. We conclude that leptin 'resistance' associated with obesity cannot be accounted for by reduced free leptin concentrations in serum and that the methods described are suitable for the investigation of total, free and bound leptin for both clinical and research purposes.

Body Mass Index↗

The management of dysphasia in skeletal hyperostosis.

Diffuse idiopathic skeletal hyperostosis (DISH), or Forestier's disease, is an ossifying condition frequently encountered in otolaryngology as it affects 12-28 per cent of the adult population. This form of hyperostosis can manifest clinically with dysphagia, food impaction, hoarseness, stridor, myelopathies and other neurological problems. Judicious management of severe dysphagia proves challenging. The failure of conservative care often leaves surgery as the only option. In this report an anterolateral transcervical surgical approach to the confluent osteophytes is discussed and the value of videofluoroscopic swallow highlighted.

Aged↗

Detecting nonlinearity in psychological data: techniques and applications.

Modern graphical and computational techniques for detecting nonlinearity in psychological data sets are presented. These procedures allow researchers to determine the information complexity of temporal data, using physiological and psychological measurements, and to provide evidence for chaos in time series contaminated by measurement noise. Problems with noise reduction and appropriate experimental control, using surrogate time series, are discussed, and applications of the technology are illustrated, using response time, handwriting, and typing data sets. In an experimental application of appropriate nonlinear analysis procedures, the results of a time series prediction experiment confirm that some subjects are sensitive to chaos. In contrast to previous attempts demonstrating sensitivity to chaos, the experiment reported here employs surrogate series to control for linear stochastic aspects of the stimulus sequences, such as autocorrelation. Recommendations for the selection of appropriate software for performing nonlinear analyses are presented, including a comprehensive list of World-Wide Web sites offering such software.

Behavioral Sciences↗

Women and cardiovascular disease.

Cardiovascular disease remains the number one killer in the United States. The face of the person with cardiovascular disease is changing. No longer is the middle-aged man at highest risk. Current data reveal that women, especially postmenopausal women, are at highest risk for cardiovascular disease. This article identifies the differences noted between men and women with cardiovascular disease, including effects in presentation, identification, and treatment.

Clinical Trials as Topic↗

The flavohemoglobin of Escherichia coli confers resistance to a nitrosating agent, a "Nitric oxide Releaser," and paraquat and is essential for transcriptional responses to oxidative stress.

Escherichia coli possesses a flavohemoglobin (Hmp), product of hmp, the first microbial globin gene to be sequenced and characterized at the molecular level. Although related proteins occur in numerous prokaryotes and eukaryotic microorganisms, the function(s) of these proteins have been elusive. Here we report construction of a defined hmp mutation and its use to probe Hmp function. As anticipated from up-regulation of hmp expression by nitric oxide (NO), S-nitrosoglutathione (GSNO) or sodium nitroprusside (SNP), the hmp mutant is hypersensitive to these agents. The hmp promoter is more sensitive to SNP and S-nitroso-N-penicillamine (SNAP) than is the soxS promoter, consistent with the role of Hmp in protection from reactive nitrogen species. Additional functions for Hmp are indicated by (a) parallel sensitivity of the hmp mutant to the redox-cycling agent, paraquat, (b) inability of the mutant to up-regulate fully the soxS and sodA promoters in response to oxidative stress caused by paraquat, GSNO and SNP, and (c) failure of the mutant to accumulate reduced paraquat radical after anoxic growth. We conclude that Hmp plays a role in protection from nitrosating agents and NO-related species and oxidative stress. This protective role probably involves direct detoxification of those species and sensing of NO-related and oxidative stress.

Bacterial Proteins↗

Activation of tyrosine receptor kinase plays a role in expression of long-term potentiation in the rat dentate gyrus.

Long-term potentiation (LTP) in perforant path-granule cell synapses has been shown to be accompanied by an increase in glutamate release. The objective of this study was to examine the possibility that nerve growth factor (NGF), by activating tyrosine kinase, modulates glutamate release and, therefore, contributes to expression of LTP in dentate gyrus. The data indicate that NGF, in the presence of trans-1-aminocyclopentyl-1,3-dicarboxylate (ACPD), enhanced KCI-stimulated release and KCI-stimulated calcium influx in vitro and that these effects were blocked by the tyrosine receptor kinase (trk) inhibitor tyrphostin AG879. The data also indicate that NGF increased phosphorylation of trkA and the mitogen-activated protein kinase extracellular signal-regulated kinase (ERK) in dentate gyrus in vitro. In addition to its effects in vitro, tyrphostin AG879 inhibited the expression of LTP in perforant path-granule cell synapses and the accompanying increase in transmitter release. Analysis of phosphorylation of the two tyrosine kinase substrates trkA and ERK in synaptosomes prepared from untetanized and tetanized dentate gyrus revealed that LTP was associated with increased phosphorylation of both proteins; no evidence of such a change was observed in either tetanized or untetanized tissue prepared from tyrphostin-pretreated rats. These findings are consistent with the hypothesis that NGF, by interacting with trkA, triggers a sequence of tyrosine kinase-dependent phosphorylation steps that modulate glutamate release and calcium influx and impact on expression of LTP in dentate gyrus.

Animals↗

Activation of p42 mitogen-activated protein kinase by arachidonic acid and trans-1-amino-cyclopentyl-1,3- dicarboxylate impacts on long-term potentiation in the dentate gyrus in the rat: analysis of age-related changes.

Maintenance of long-term potentiation in perforant path-granule cell synapses is associated with an increase in glutamate release, which we have suggested relies on an interaction between arachidonic acid and the metabotropic glutamate receptor agonist, trans-1-amino-cyclopentyl-1,3-dicarboxylate (ACPD). Evidence suggests that this interaction is dependent on stimulation of tyrosine kinase, which phosphorylates and activates phospholipase Cgamma. In this study, we demonstrate that arachidonic acid and ACPD stimulate tyrosine phosphorylation of a protein of about 40,000 mol. wt and further analysis, using a specific antibody, suggested that this may be extracellular signal-regulated kinase, one member of the family of mitogen-activated protein kinases. Activity of extracellular signal-regulated kinase was increased by arachidonic acid and ACPD in vitro, but it was also increased by induction of long-term potentiation in perforant path-granule cell synapses. A role for extracellular signal-regulated kinase in long-term potentiation was supported by the observation that expression of long-term potentiation, as well as the associated increases in endogenous glutamate release and extracellular signal-regulated kinase activation, were inhibited by pretreatment with the mitogen-activated protein kinase inhibitor, PD98059, while PD98059 pretreatment inhibited the interaction between arachidonic acid and ACPD on glutamate release. An age-related decrease in extracellular signal-regulated kinase activity was observed in the dentate gyrus, and there was no evidence of increased extracellular signal-regulated kinase activity or endogenous glutamate release in tissue prepared from aged rats in which long-term potentiation was compromised. The evidence is consistent with the view that increased activation of extracellular signal-regulated kinase plays a role in long-term potentiation, and that activation of this kinase relies on the interaction between arachidonic acid and ACPD.

Aging↗

A nursing intervention to decrease depression in family caregivers of persons with dementia.

The goal of this study was to evaluate a community-based psychoeducational-nursing intervention designed to teach home caregivers to manage behavioral problems of persons with Alzheimer's disease and related dementias (ADRD) using the Progressively Lowered Stress Threshold (PLST) model, and to compare this intervention with routine information and referrals for case management, community-based services, and support groups. Previous caregiver studies have overwhelmingly pointed to the adverse effects of caregiving on the caregivers' physical and mental health, and high prevalence rates of depression among caregivers of persons with ADRD have consistently been reported. Therefore, a primary aim was to evaluate the impact of the intervention on caregivers' affective responses, especially depression. Data from both the Profile of Moods States and the Geriatric Depression Rating Scale support the effectiveness of this intervention in decreasing depression among caregivers who received the experimental training. Additional analysis of factors associated with caregiver depression are also reported. The pivotal role of psychiatric nurses in the assessment and treatment of depression among caregivers of persons with ADRD is discussed.

Adaptation, Psychological↗

Effects of stocking density and concentrate supplementation of grazing dairy cows on milk production, composition and processing characteristics.

The effects on milk composition and processing characteristics of varying grass supply by changing stocking density and of offering a concentrate supplement were investigated. The experiment was conducted over 28 weeks of the lactation (April-October) using 48 spring-calved Friesian-Holstein cows. Three herds each of 16 cows were offered a restricted grass supply, a standard grass supply and a standard grass supply with a supplement of 3 kg concentrate/d. Treatment groups were grazed separately with a residence time of 3 d/paddock. Milk production, composition and processing characteristics such as renneting properties, ethanol stability and plasmin activity were measured weekly. Increasing stocking density above the standard system resulted in significant reductions in milk fat and protein yields, the concentrations of total protein, casein and whey proteins, and a deterioration in most processing characteristics. Imposing concentrate supplementation on the standard system increased total protein, casein and whey protein concentrations but generally did not improve processing characteristics except for ethanol stability. These results suggest that the standard grass supply in a rotational grazing paddock system can support efficient production of quality milk, and concentrate supplementation will not improve processing characteristics when an adequate supply of good quality herbage is available.

Animal Feed↗