Biomedical subjects

A Kelly

Publications and source records attributed to A Kelly.

At least 19 recordsLinked to original sources

PubMed2005

Predictors of antral follicle count during the reproductive years.

BACKGROUND: We sought to identify indicators of antral follicle count which would be serviceable to clinicians seeking to estimate the number of ovarian follicles without relying on sonographic counts. METHODS: We examined the relations of chronological age and four potential indicators of ovarian age-ovarian volume, FSH, dimeric inhibin B and estradiol-to antral follicle count in 176 recently pregnant women. We identified the regression models which best predict low antral follicle count (< or =10 follicles). RESULTS: Chronological age, ovarian volume, FSH and inhibin B were each significantly associated with antral follicle count. Fifty-three (30.1%) women had < or =10 antral follicles. In the total sample, at the cutpoint corresponding to 80% sensitivity, the positive predictive value for a regression model with all four variables was 60%. All regression models performed less well in women <35 years (13.9% with low count) than in women > or =35 years (52.0% with low count). In older women, the positive predictive value for the model with all four variables was 79%, compared with 60% for a model with chronological age alone. CONCLUSIONS: Our models provide a basis for advising women aged > or =35 years who are either trying to conceive or wish to learn whether they may postpone childbearing.

Adult↗

PubMed2004

The relationship between circulating concentrations of C-reactive protein, inflammatory cytokines and cytokine receptors in patients with non-small-cell lung cancer.

The relationship between circulating C-reactive protein concentrations and potential cytokine and receptor mediators (interleukin-6, leukaemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), soluble IL-6 receptor, soluble gp130, soluble TNF receptor, interleukin-1 receptor antagonist and interleukin-8 (IL-8)) of this acute phase protein were examined in healthy subjects (n=11) and patients with non-small-cell lung cancer (n=50). Leukaemia inhibitory factor and CNTF were below detection limits in all controls and patients. C-reactive protein, interleukin-6, soluble gp130, soluble TNF receptor, interleukin-1 receptor antagonist and IL-8 concentrations were significantly elevated in cancer patients (P< or =0.001). Cancer patients with elevated C-reactive protein concentrations had greater concentrations of interleukin-6 (P<0.01) and interleukin-1 receptor antagonist (P<0.05). On regression analysis only interleukin-6 was independently associated with C-reactive protein (r=0.616, P<0.001). Interleukin-6 is an important independent mediator of elevated C-reactive protein concentrations in patients with non-small-cell lung cancer.

Adult↗

PubMed2004

Trisomic pregnancy and the oocyte pool.

BACKGROUND: We tested the hypothesis that trisomy risk is increased for women with fewer oocytes (older ovarian age) than other women of the same chronological age. METHODS: Our study compared three indicators of ovarian age-number of antral follicles, level of dimeric inhibin B, level of FSH-among women who had trisomic pregnancy losses (n = 54) with those among women who had other losses (24 with other chromosomally abnormal loses, 21 with chromosomally normal losses) or who had chromosomally normal births (n = 65). RESULTS: Ovarian age indicators did not differ between women with trisomic spontaneous abortions and the three comparison groups. Compared with live birth controls, adjusting for chronological age, we estimate that, on average, among trisomy cases the geometric means of 1 + follicle count, inhibin B and FSH are about 7.5% higher, 16.6% higher and 5.5% lower, respectively, with all 95% confidence intervals including zero. The sample size was sufficient to detect moderate differences (0.52 standard errors of regression) between trisomy cases and live birth controls. CONCLUSIONS: Although our data do not support our hypothesis, they leave open the possibility that changes in follicular development unrelated to the size of the oocyte pool influence abnormal chromosome segregation.

Abortion, Spontaneous↗

PubMed2004

Evaluation of painful hydronephrosis in pregnancy: magnetic resonance urographic patterns in physiological dilatation versus calculous obstruction.

PURPOSE: We evaluated magnetic resonance urography (MRU) appearances in symptomatic hydronephrosis in pregnancy and compared urographic patterns in physiological and calculous disease. MATERIALS AND METHODS: A total of 24 consecutive pregnant women with symptomatic hydronephrosis underwent MRU, comprising an overview fast T2-weighted examination of the abdomen and pelvis, and thick slab, heavily T2-weighted MRU images, followed by focused, high resolution T2-weighted sequences obtained in an axial and coronal oblique plane through the level of ureteral caliber change. RESULTS: Of these 24 pregnant women 15 were found to have physiological hydronephrosis, 7 had calculous disease and 2 had preexisting urinary anomalies. MRU findings in physiological hydronephrosis cases were extrinsic compression of the middle third of the ureter, no filling defect and a collapsed ureter below it. Obstruction by ureteral calculi was seen at points of ureteral narrowing in the ureter, that is at the vesicoureteral junction in 2 cases, in the compressed mid ureter in 3 and at the pelviureteral junction in 1. Nonobstructive renal calculi were seen in another patient. Calculi presented throughout pregnancy but physiological hydronephrosis presented only in the late second and third trimesters. With distal calculi the MRU appearance was the double kink sign with constriction at the pelvic brim and the vesicoureteral junction with a standing column of urine in the pelvic ureter. There was renal edema and perirenal extravasation. Small calculi were only identified using high resolution T2-weighted magnetic resonance imaging. CONCLUSIONS: MRU is a valuable and well tolerated investigation for evaluating painful hydronephrosis in pregnancy. There are characteristic and differing urographic appearances in physiological and calculous obstruction.

Adolescent↗

PubMed2004

Congenital anomalies and proximity to landfill sites.

The occurrence of congenital anomalies in proximity to municipal landfill sites in the Eastern Region (counties Dublin, Kildare, Wicklow) was examined by small area (district electoral division), distance and clustering tendancies in relation to 83 landfills, five of which were major sites. The study included 2136 cases of congenital anomaly, 37,487 births and 1423 controls between 1986 and 1990. For the more populous areas of the region 50% of the population lived within 2-3 km of a landfill and within 4-5 km for more rural areas. In the area-level analysis, the standardised prevalence ratios, empirical and full Bayesian modelling, and Kulldorff's spatial scan statistic found no association between the residential area of cases and location of landfills. In the case control analysis, the mean distance of cases and controls from the nearest landfill was similar. The odds ratios of cases compared to controls for increasing distances from all landfills and major landfills showed no significant difference from the baseline value of 1. The kernel and K methods showed no tendency of cases to cluster in relationship to landfills. In conclusion, congenital anomalies were not found to occur more commonly in proximity to municipal landfills.

Bayes Theorem↗

PubMed2004

The potential impact on travel times of closure and redistribution of A&E units in Ireland.

Modelling has been used to estimate variations in travel time to Accident & Emergency (A&E) Departments for Acute Myocardial Infarction (AMI) and Road Traffic Accidents (RTA), taking into account three different distributions of A&E departments in the country. We have modelled three scenarios: current, the current distribution of A&E Departments; intermediate, two A&E Units for some Health Boards and one for others; and extreme, one A&E Department for each of the 10 Health Boards. The percentage of travel times that fall within an hour for AMI and RTA for the three scenarios (current, intermediate and extreme) are 85.6, 82.8, 70.0 and 81.8, 85.2, 71.8 percent respectively. While a redistribution of A&E Departments seems inevitable, a sensible modelling approach can be used to plan the new distribution of services to maintain equitable geographic access.

Accidents, Traffic↗

PubMed2003

Synaptophysin immunogold labelling of synapses decreases in dentate gyrus of the hippocampus of aged rats.

Synaptophysin expression was assessed in dentate gyrus prepared from aged (22 months) and young (4 months) rats by immunoblotting and post-embedding immunolabelling at electron microscope level. Immunoblotting showed qualitatively that there was a marked reduction in synaptophysin expression in synaptosomes of aged compared with young rats. Immunogold labelling studies in the medial molecular layer of the dentate gyrus demonstrated that gold particles were restricted to pre-synaptic boutons, and were present mainly on the membranes of the synaptic vesicles or occasionally inside vesicles. In aged rats, immunolabelling patterns and the density of immunogold particles per pre-synaptic bouton were almost 50% lower than in younger rats. However, because boutons were larger in older rats the actual labelling density per unit area of bouton (3.77) was even lower than in the young rats (7.74). The role of synaptophysin in neural plasticity and ageing should be further examined.

Aging↗

PubMed2003

Influence of material deprivation on prescribing patterns within a deprived population.

OBJECTIVE: To study the effect of material deprivation on prescribing trends in primary care, using a locally derived deprivation score. METHODS: A retrospective analysis of prescribing trends linked to material deprivation by district electoral division (DED) in the Eastern Region of the General Medical Services in Ireland (population of 334,031) was performed. Standardised prescribing ratios were determined for a number of drug classes, including those that could be used to identify particular diseases for 181,647 patients who were assigned a locally derived material deprivation score. RESULTS: Prescribing rates for a number of medications including anti-asthma, nitrate and benzodiazepine medications increased, whilst the prescribing of other medications such as anti-parkinsonian and antidepressive agents decreased with increasing deprivation. CONCLUSIONS: Our results suggest that, even within a population considered to be economically deprived, different levels of deprivation may significantly influence general practitioner prescribing patterns. Within the group of centrally active medications, the prescription of symptomatic medications increased with increasing material deprivation, whilst the prescription of disease-specific medications decreased with increasing material deprivation.

Cultural Deprivation↗

PubMed2003

Early and late outcome after carotid artery bypass grafting with saphenous vein.

OBJECTIVES: This study was undertaken to determine outcome and durability of internal carotid artery bypass grafting with saphenous vein. METHODS: Data for 50 patients undergoing serial clinical and ultrasound surveillance were collected prospectively and analyzed retrospectively. RESULTS: Bypass grafting was performed in 50 patients between 1995 and 2002, the commonest reasons being excessive endarterectomy zone thinning or penetrating atheroma (n = 22), severe internal carotid artery coiling above the endarterectomy zone (n = 14), and patch infection (n = 5). Perioperative mortality was 2%, and death and stroke rate was 6%. Perioperative complications were associated with complex cardiovascular events, including hemorrhage after prosthetic patch infection, on-table thrombosis after endarterectomy, and synchronous carotid artery-cardiac reconstruction. One patient had a late ipsilateral stroke (10 months; normal scan). Cumulative stroke-free survival at 3 years (including operative events) was 91%. Cumulative freedom from recurrent stenosis greater than 70% or occlusion was 86% at 1 year and 83% at 3 years. Severe recurrent stenosis or occlusion developed in 7 patients, within 9 months of surgery in 6 patients and with 18 months in 1 patient. Angioplasty was performed without complication (no protection device, no stent) in 5 patients, 3 of whom required repeat angioplasty on at least one further occasion. CONCLUSIONS: In common with venous conduits elsewhere, carotid artery bypass grafting with saphenous vein is associated with a high incidence of early graft stenosis. The long-term stroke risk, however, is low. Carotid artery bypass grafting is a safe and durable alternative when endarterectomy would prove hazardous or inadvisable, but regular surveillance is necessary.

Blood Vessel Prosthesis Implantation↗

PubMed2003

The impact of a vertically transmitted microsporidian, Nosema granulosis on the fitness of its Gammarus duebeni host under stressful environmental conditions.

Although purely vertically transmitted parasites are predicted to cause low pathogenicity in their hosts, the effects of such parasites on host fitness under stressful environmental conditions have not previously been assessed. Here, we investigate the effects of Nosema granulosis, a vertically transmitted, microsporidian parasite of the brackish water amphipod Gammarus duebeni, on host growth and survival under conditions of host-host competition and limited food. The parasite had no effect on host survival, but caused a reduction in juvenile growth. Stressful environmental conditions also led to a reduction in G. duebeni growth. However, we found no evidence to support the prediction that parasitized hosts would suffer a greater reduction in fitness than uninfected hosts under adverse environmental conditions. We interpret our results in the context of selection for successful vertical parasite transmission.

Amphipoda↗

PubMed2003

Using simulated patients in a multiprofessional communications skills programme: reflections from the programme facilitators.

This paper discusses a multiprofessional, 4-day communication skills programme in which participants explore the challenges of communicating with cancer patients and their families. Effective communication and skilled emotional support are essential prerequisites for high quality care in oncology and palliative care settings. This aspect of care presents major challenges to nurses and other health care professionals. It is acknowledged that health professionals often lack the requisite skills to communicate meaningfully with this patient group and that tangible benefits accrue from training in this area. Using simulated patients, structured feedback and small group discussions, this multiprofessional programme seeks to provide a forum that enables participants to acquire confidence and competence in a safe, comfortable and non-threatening environment. The programme structure presents several challenges in terms of providing a learning experience that addresses the diverse educational of a heterogeneous learning group. Participants' comments and programme facilitators reflections suggest that the programme is successful in addressing these challenges and providing a meaningful learning experience.

Clinical Competence↗

PubMed2002

Incomplete feminisation by the microsporidian sex ratio distorter, Nosema granulosis, and reduced transmission and feminisation efficiency at low temperatures.

We investigated the effects of temperature on transovarial transmission and feminisation by Nosema granulosis, a microsporidian sex ratio distorter of the brackish water amphipod Gammarus duebeni. There was no difference in parasite transmission efficiency to the F(1) eggs of infected females maintained under two temperature conditions, 5 and 10 degrees C (89 and 86%, respectively). When F(1) individuals were screened as adults, the proportion infected was also similar at both temperatures (74 and 75%, respectively). However, transmission to the eggs of the F(2) generation was significantly reduced at low temperatures (61% at 5 degrees C and 91% at 10 degrees C). In addition, feminisation efficiency was reduced substantially at low temperatures; at 10 degrees C, a calculated 85% of infected males were feminised, but at 5 degrees C only 49% were feminised. This is the first evidence for incomplete feminisation and temperature-dependent transmission and feminisation by this sex ratio distorter. We examine the consequences for parasite spread and maintenance in natural populations using a model to predict parasite prevalence in large populations. Reduced feminisation at low temperatures impedes the spread of the parasite so that it attains a substantially lower frequency, or may even be excluded, from host populations.

Animals↗

PubMed2002

Analysis of the presynaptic signaling mechanisms underlying the inhibition of LTP in rat dentate gyrus by the tyrosine kinase inhibitor, genistein.

A great deal of recent evidence points to a role for tyrosine kinase in expression of LTP. Data have been presented that are consistent with the idea that tyrosine phosphorylation of proteins occurs in both the presynaptic and postsynaptic areas. In this study, we set out to investigate the role that tyrosine kinase might play presynaptically to modulate release of glutamate in an effort to understand the mechanism underlying the persistent increase in release that accompanies LTP in perforant path-granule cell synapses. We report that LTP was associated with increased calcium influx and glutamate release. LTP was also associated with an increase in phosphorylation of the alpha-subunit of calcium channels and ERK in synaptosomes prepared from dentate gyrus, and these effects were inhibited when LTP was blocked by the tyrosine kinase inhibitor, genistein. LTP was accompanied by increased protein synthesis and increased phosphorylation of CREB in entorhinal cortex, effects that were also blocked by genistein. We conclude that tetanic stimulation leads to enhanced tyrosine phosphorylation of certain presynaptically located proteins that modulate glutamate release and contribute to expression of LTP.

Animals↗

PubMed2002

Long-term potentiation and spatial learning are associated with increased phosphorylation of TrkB and extracellular signal-regulated kinase (ERK) in the dentate gyrus: evidence for a role for brain-derived neurotrophic factor.

In this study, the authors investigate changes in the presynaptic terminal of the dentate gyrus that accompany 2 types of hippocampal-dependent plasticity: spatial learning and long-term potentiation (LTP). Parallel changes occurred in the dentate gyrus of rats that had undergone training in the Morris water maze and had sustained LTP. In both cases, KCl-induced brain-derived neurotrophic factor release was increased, and this was accompanied by increased phosphorylation of TrkB and the mitogen-activated protein kinase, ERK. Glutamate release was also enhanced, and the data suggest that this may be a consequence of increased activation of TrkB and ERK. Because the data indicate that similar cellular modifications are shared by these 2 forms of plasticity, they provide circumstantial evidence that LTP satisfies some of the requirements of a memory-inducing cellular substrate.

Animals↗

PubMed2002

Neoadjuvant treatment of advanced stage esophageal adenocarcinoma increases survival.

Sophisticated surgical approaches have a definite but limited role in esophageal cancer. The majority have systemic disease at presentation, minimal residual disease following resection or co-morbid conditions that preclude extensive surgery. This paper examines whether neoadjuvant therapy is effective in advanced-stage disease. A randomized trial, closing September 1995, was followed up to determine results at 5 years. All patients were followed up for more than 5 years. Median survival, based on intention-to-treat, was 17 months for multimodal therapy vs. 12 months for surgery alone (P=0.002). Survival based on treatment received was 27 months vs. 14 months (P=0.0006). Multimodal therapy enhances survival for patients with minimal residual disease. This is consistent with the literature. Under-powered trials cannot prove a real difference to be significant. Future trials should target patients with minimal residual disease.

Adenocarcinoma↗

PubMed2002

Assessment and management of fatigue in patients with advanced cancer: developing guidelines.

Cancer-related fatigue is one of the most important untreated symptoms of cancer, with a prevalence between 60 and 100%, but there has been a reluctance to prioritize fatigue and develop effective management strategies. The development of standards and guidelines will encourage a more systematic approach and help to stimulate further research. The Mersey Palliative Care Audit Group has developed guidelines for the assessment and management of fatigue. These guidelines were produced following a regional survey, which looked at both the educational needs of nurses, and the impact of fatigue on patients with advanced cancer.

England↗

PubMed2002

Survival and normal function of glycolysis-deficient mouse oocytes.

Mouse embryos homozygous for a null allele of Gpi1 which encodes the glycolytic enzyme glucose phosphate isomerase fail to complete gastrulation and die at about embryonic day 7.5, but mutant cells can survive in fetal chimaeras in which they are mixed with wild-type cells. An adult female mouse chimaera, composed of wild-type cells and homozygous Gpi1(-/-) null mutant cells, was produced to test whether the presence of wild-type cells in the ovary allowed mutant oocytes to survive and function. This mouse produced 28 offspring, eight of which were derived from homozygous Gpi1(-/-) null oocytes. DNA in situ hybridization also showed that some Gpi1(-/-) follicle cells were able to survive in chimaeric ovarian follicles. It is likely that the survival of mutant follicle cells and fully functional mutant oocytes was mediated by the presence of wild-type cells that could provide metabolic intermediates and so bypass the block in the glycolytic pathway. Wild-type cumulus cells probably supported the growing GPI-deficient oocytes via metabolic co-operation, by passing ATP and other glycolytic products through gap junctions. It was concluded that female mouse germ cells and ovarian follicle cells do not need an intact endogenous glycolytic pathway if they can obtain appropriate metabolites from an exogenous source.

Anemia, Hemolytic, Congenital Nonspherocytic↗

PubMed2002

Differential expression of human chorionic gonadotropin (hCG) glycosylation isoforms in failing and continuing pregnancies: preliminary characterization of the hyperglycosylated hCG epitope.

Human chorionic gonadotropin (hCG) glycoforms change as pregnancy progresses. We have developed an antibody (B152) which can measure a hyperglycosylated early pregnancy isoform of hCG. This putative hyperglycosylated form of hCG arises very early in pregnancies and is rapidly replaced by an isoform that predominates for the remainder of the pregnancy. The profiles of these hCG glycoforms are measured as a ratio of values of two immunometric assays. The profiles of these ratios differ between pregnancies which persist and those which will experience early failure. In this report, daily urine hCG isoform ratios from donor eggs (no exogenous hCG pretreatment), in vitro fertilization pregnancies were profiled and analyzed from the first day following embryo transfer (ET). Significant differences were found between continuing pregnancy and pregnancy loss throughout days 5-20 post-ET. When hCG isoform ratios were analyzed from the first day of detectable hCG, pregnancy loss could be predicted in the case of a single fetus both during the 5- to 10-day time segment (P=0.018) and the 10- to 15-day time segment (P=0.045). When single and multiple fetus pregnancies were analyzed together significance was approached in the 10- to 15-day time period (P=0.058). In a second population of pregnant women who conceived naturally, in whom urine samples were collected at approximately weekly intervals to either term birth or clinical spontaneous abortion, the ratio could discriminate between miscarriages and normal term pregnancies (P=0.043). In later pregnancy, the ratio of hCG isoforms declined more rapidly in miscarriages than in term pregnancy. Antibody B152 was produced using a choriocarcinoma-derived hCG (C5), which was hyperglycosylated at both N- and O-linked sites and was 100% nicked at position beta(47-48). Western blot analyses supported the assay results showing that early pregnancy urine does not contain nicked C5-like hCG. Also, the early pregnancy hCG appeared to be the same size as later pregnancy hCG as judged by SDS gel electrophoresis. A series of Western blot analyses and immunoassays conducted with the samples either non-reduced or reduced showed that B152 is directed to a linear epitope located in the COOH-terminal peptide region of the beta subunit. This indicated that only the O-glycan groups and not the N-linked glycans are part of the antibody epitope.

Abortion, Spontaneous↗