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Biomedical subjects

L Brennan

Publications and source records attributed to L Brennan.

At least 37 records · Page 2Linked to original sources

Factors associated with physical activity in women across the life span: implications for program development.

This study examined the rates and factors associated with physical activity in women of various ages. Adult women (n = 653) from four community-based family medicine clinics completed a self-administered behavioral and health questionnaire while waiting to see their physician. Findings suggested variation in physical activity over the life span, with older women performing less physical activity than younger women. Family characteristics (e.g., having children) were strongly associated with performing less structured, less intense physical activities of daily living among women 49 years and younger. Younger women reported having high self-efficacy for physical activity, but also reported the greatest numbers of barriers. Women in the oldest age category reported health as the most common motivator for physical activity, but were also least likely to perform physical activity. Interventions designed to meet the unique needs of women at different stages in their lives will potentially reduce the rate of inactivity among women. Creative, flexible strategies that incorporate physical activity into the daily routine should be used in the program development.

Adult↗

Preoperative education and outcome of patient controlled analgesia.

PURPOSE: To determine the effect of intensive preoperative education on the outcome of Patient Controlled Analgesia (PCA) postoperatively. METHODS: This prospective randomised study was carried out in a single teaching hospital over three months. One group of patients (n = 42) received a 20 min standardised tutorial regarding PCA use from a single investigator and the other group (n = 43) received no additional education apart from the routine preoperative anaesthetic consultation. A blinded investigator assessed the patients following surgery. Pain scores and morphine consumption, patient satisfaction, side-effect profile and anti-emetic use were recorded at six, 24 and 48 hr postoperatively. RESULTS: Pain scores, satisfaction scores and morphine consumption were similar in both groups throughout the study period. Fewer patients in the tutored group complained of nausea from 6 to 24 hr than did untutored patients (28% vs 51%; P < 0.05). More tutored patients used antiemetic medication from 0 to 6 (28% vs 12%; P < 0.05) and 6 to 24 hr (37% vs 19%; P < 0.05). Side effect profile and requirement for rescue analgesia was otherwise similar in both groups. CONCLUSION: Our results suggest that specific preoperative education of patients using PCA does not alter pain scores, morphine consumption or patient satisfaction but may result in earlier and more effective use of anti-emetic medication.

Analgesia, Patient-Controlled↗

Determination of solution structures of paramagnetic proteins by NMR.

Standard procedures for using nuclear Overhauser enhancements (NOE) between protons to generate structures for diamagnetic proteins in solution from NMR data may be supplemented by using dipolar shifts if the protein is paramagnetic. This is advantageous since the electron -nuclear dipolar coupling provides relatively long-range geometric information with respect to the paramagnetic centre which complements the short-range distance constraints NOEs. Several different strategies have been developed to date, but none of these attempts to combine data from NOEs and dipolar shifts in the initial stages of structure calculation or to determine three dimensional protein structures together with their magnetic properties. This work shows that the magnetic and atomic structures are highly correlated and that it is important to have additional constraints both to provide starting parameters for the magnetic properties and to improve the definition of the best fit. Useful parameters can be obtained for haem proteins from Fermi contact shifts; this approach is compared with a new method based on the analysis of dipolar shifts in haem methyl groups with respect to data from horse and tuna ferricytochromes c. The methods developed for using data from NOEs and dipolar shifts have been incorporated in a new computer program, PARADYANA, which is demonstrated in application to a model data set for the sequence of the haem octapeptide known as microperoxidase-8.

Anisotropy↗

Paramagnetic NMR shifts in cyanoferricytochrome c. Investigation of thermal stability and deviations from Curie law behaviour.

The paramagnetic shifts of 13C nuclei positioned alpha to the haem in cyanoferricytochrome c are reported and analysed in terms of molecular orbitals based on D4h symmetry with a rhombic perturbation. The temperature dependence of the Fermi contact and dipolar shifts of the haem and axial histidine ligand show deviations from Curie Law behaviour which are explained by a Boltzmann distribution between partially filled 3e(pi) molecular orbitals and the ground and first excited state Kramers doublets. The comprehensive explanation of the temperature dependence of the paramagnetic shifts leads to the conclusion that there is no detectable temperature dependence of the haem orientation or that of the His ligand orientation. This work also provides evidence for the role of the axial His ligand in determining the orientation of the magnetic z-axis.

Cytochrome c Group↗

Refined mapping and YAC contig construction of the X-linked cleft palate and ankyloglossia locus (CPX) including the proximal X-Y homology breakpoint within Xq21.3.

The gene for X-linked cleft palate (CPX) has previously been mapped in an Icelandic kindred between the unordered proximal markers DXS1002/DXS349/DXS95 and the distal marker DXYS1X, which maps to the proximal end of the X-Y homology region in Xq21.3. Using six sequence-tagged sites (STSs) within the region, a total of 91 yeast artificial chromosome (YAC) clones were isolated and overlapped in a single contig that spans approximately 3.1 Mb between DXS1002 and DXYS1X. The order of microsatellite and STS markers in this was established as DXS1002-DXS1168-DSX349-DXS95-DXS364-DXS 1196-DXS262-DXS110-DXS1066-(DXS1169, DXS1222)-DXS472-DXS1217-DXYS1X. A long-range restriction map of this region was created using eight nonchimeric, overlapping YAC clones. Analysis of newly positioned polymorphic markers in recombinant individuals from the Icelandic family has enabled us to identify DXS1196 and DXS1217 as the flanking markers for CPX. The maximum physical distance containing the CPX gene has been estimated to be 2.0 Mb, which is spanned by a minimum set of five nonchimeric YAC clones. In addition, YAC end clone and STS analyses have pinpointed the location of the proximal boundary of the X-Y homology region within the map.

Base Sequence↗

Low expression of the Lsp1 gene in early mouse T-lymphomas induced by N-methyl-N-nitrosourea.

The mouse Lsp1 gene encodes a 330 amino acid intracellular F-actin binding protein. Previously we showed that the mouse and human Lsp1 genes are expressed in normal B-cells and T-cells, including Thy1+ thymocytes and in normal macrophages and neutrophils. No or little LSP1 RNA and protein was found in a series of transformed mouse and human T-lymphoma cell lines, although normal antigen and lymphokine dependent T-cell lines expressed the Lsp1 gene. Here we show by Northern analysis that three mature antigen independent T-cell lines (CTLL-2, HT-2 and 532.10) which grow in the presence of lymphokine only, do not express LSP1 RNA, while mature resting and activated lymph node T-cells express high levels of LSP1 RNA. To determine whether the down-regulation of LSP1 expression is an early event which occurs in vivo in the tumor, rather than as a consequence of in vitro propagation of T-lymphoma cells, we analyzed LSP1 expression in primary T-lymphomas induced in AKR/J or AKR/J x BALB/cJ mice by a single intraperitoneal (i.p.) injection with 75 mg N-methyl-N-nitrosourea (MNU) per kg body-weight. Two- color Fluorescence Activated Cell Sorter (FACS) analysis showed that all tumors had an immature CD4+/CD8+ double positive (DP) phenotype. Many tumors contained a substantial population of CD4+ single positive (SP) cells. Since these cells may be infiltrating lymphocytes which can be expected to express the Lsp1 gene at a high level these tumors were not included in our analysis. Nineteen tumors were analyzed for Lsp1 gene expression and 13 contained reduced levels of LSP1 RNA, ranging from 4% to 44% of those found in age-matched normal thymus. Six tumors showed either no or only a small reduction in LSP1 RNA. These tumors had developed later than those expressing low levels of LSP1. The level of LSP1 RNA in tumors developing <110 days after injection of MNU was 19.1% +/- 5.2 (mean +/- SEM), while the level of LSP1 in later tumors was 78.4% +/- 13.0 (P = 0.004). Similar data were obtained when the expression of LSP1 protein was analyzed. These findings extend our previous data in several ways. First, they suggest a correlation between the down-regulation of LSP1 expression and abnormal regulation of growth or survival of immature and mature T-lymphocytes. Second, they show that down-regulation of the Lsp1 gene in transformed T-cells is not the result of prolonged in vitro culture, but occurs in the majority of primary tumors. Third, they show that there are two classes of T-lymphoma, which differ in their expression of LSP1 RNA and that the down-regulation of LSP1 is specifically associated with the early appearance of T-lymphoma after injection with MNU. This strongly suggests that the absence or reduced expression of LSP1 contributed to the transformation process and argues against the possibility that loss of LSP1 expression is a mere inconsequential epigenetic event.

Animals↗

Refinement of the X-linked cleft palate and ankyloglossia (CPX) localisation by genetic mapping in an Icelandic kindred.

The gene responsible for X-linked cleft palate and ankyloglossia (CPX) has previously been localized to the proximal region of the q arm of the X chromosome in both Icelandic and North American Indian kindreds. In this study, further linkage analysis has been performed on the Icelandic family and has resulted in a significant reduction in the size of the interval containing the mutated gene. A new polymorphism at DXS95, together with DXS1002 and DXS349, defines the proximal boundary of the CPX interval, whereas DXYS1X defines the distal boundary. Multipoint analysis supports this localisation with a peak lod score of 12.7, more than 2 lod score units higher than the next most likely position. In order to assess the physical size of the CPX interval prior to initiating yeast artificial chromosome cloning, metaphase fluorescence in situ hybridisation analysis was performed with the closest flanking markers. The size of the interval between DXS95 and DXYS1X was estimated to be approximately 2-3 Mb.

Chromosome Mapping↗

Postal survey of paediatric practice and training among consultant anaesthetists in the UK.

A postal survey of previous paediatric anaesthetic training, current paediatric experience and management of an infant pyloromyotomy was undertaken among consultant anaesthetists in the UK. A total of 851 questionnaires were returned, giving a response rate of 31%; 352 (41%) consultants had at least one paediatric list each week, 180 (21%) anaesthetized more than one infant less than 6 months old each month and 373 (44%) had obtained more than 6 months' specialist training. Consultants trained most recently had received significantly longer (P < 0.001) specialist training than their senior colleagues: 558 (66%) consultants dealt with infants requiring a pyloromyotomy, 348 with one or two cases annually. Two-thirds preferred to use an i.v. induction technique and less than half used cricoid pressure. Choice of technique was related to the duration of specialist paediatric training and when it was received, but not to current paediatric anaesthetic experience. The results are discussed in relation to recently published recommendations on paediatric anaesthetic services.

Anesthesia↗

Elevated serum homocysteine as a predictor for vitamin B12 or folate deficiency.

Tissue deficiency of vitamin B12 and folate results in an increase in serum homocysteine (sHcy). We have measured sHcy in patients with reduced serum vitamin B12 and/or red cell folate (RCF) to determine its usefulness as a discriminant for the diagnostic interpretation of reduced vitamin levels. Of 3846 patients who had serum vitamin B12 and RCF assayed, 335 (9%) had reduced vitamin levels. Multivariate analysis showed a significant association between sHcy and serum creatinine (p = 0.0001), positive intrinsic factor (IF) antibody or neutrophil hypersegmentation (NHS) (p = 0.001), increased MCV (p = 0.014) and low RCF (p = 0.025) but no relationship with the level of serum vitamin B12 or haemoglobin. After censoring the patients with renal impairment (n = 54), the distribution of the remaining 72 patients with elevated sHcy was 37/151 (25%) with low serum vitamin B12 with or without low RCF and 35/130 (27%) with low RCF alone. sHcy correctly identified response to vitamin therapy in 33/35 (94%) patients who had adequate parameters to assess response. The positive predictive values of IF antibody/NHS, macrocytosis and/or low RCF for elevated sHcy were 100% and 34% respectively. Twenty-four percent of patients with a low serum vitamin B12 and elevated sHcy had no abnormal haematologic parameters as determined by the routine laboratory staff. These data suggest that the usefulness of measuring sHcy in a routine diagnostic setting is limited and a careful review of the peripheral blood for macrocytosis and NHS plus determination of RCF may be a more cost-effective process than sHcy assay in most instances to determine the presence of tissue deficiency.

Adult↗

Major incident planning in South East Thames Region: a survey of medical staff awareness and training.

In order to assess awareness and training of medical staff in major incident planning and disaster medicine, a telephone survey was conducted throughout South East Thames Region. Duty consultants and trainees in anaesthesia, general surgery and orthopaedic surgery from a total of 17 hospitals in the region were included. Accident and emergency (A&E) consultants were also interviewed in order to assess administrative aspects of major incident planning. It was found that major incident plans were updated regularly in all the hospitals that were surveyed. Training exercises had been held in 88% of hospitals and the majority had tested communications only. All consultants and 77% of trainees knew that their hospital had a major incident plan. However, only 39% of trainees had been given any major incident plan related literature and less than a third of all staff had attended a major incident plan orientation session. Over half of all staff expressed confidence in their personal training in disaster medicine, but few had received relevant tuition. Of all non-A&E personnel, 5% had attended an Advanced Trauma Life Support (ATLS) provider course. We conclude that major incident plans are in place and are updated in all the hospitals surveyed. However, all staff lack training in clinical and administrative aspects of major incident planning and disaster medicine. Recommendations to improve this situation are made.

Awareness↗

Use of pediatric physician extenders in pediatric and neonatal intensive care units.

OBJECTIVES: To determine present and future use of pediatric physician extenders in neonatal and pediatric intensive care units (ICUs). DESIGN: Descriptive, prospective, questionnaire survey. PARTICIPANTS: One hundred thirty hospitals represented by members of the Pediatric Section of the Society of Critical Care Medicine and 18 randomly selected hospitals identified as having no pediatric intensivist. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred one (68.2%) of 148 responding institutions employed physician extenders and 69 (46.7%) employed pediatric physician extenders. Eighty percent of the hospitals using pediatric physician extenders employed pediatric nurse practitioners and 25% employed physician assistants. Of the 69 hospitals that employed pediatric physician extenders, 51 (73.9%) hospitals utilized them in neonatal ICUs and 12 (17.4%) hospitals used them in the pediatric ICUs. Institutions that did or did not employ pediatric physician extenders in pediatric ICUs were comparable in all factors studied, except for the perception of childcare physician staffing shortages. Duties competently performed by pediatric physician extenders did not differ between pediatric nurse practitioners and physician assistants and were similar to those duties of a second-year pediatric resident. More than 40% of institutions expected to increase the use of pediatric physician extenders in neonatal and pediatric ICUs and they expected to provide the majority of the specialty training required. CONCLUSIONS: Pediatric physician extenders are extensively employed in pediatric and neonatal ICUs. They are perceived to perform at the level of second-year pediatric residents and are strongly supported by staff physicians and residents. It appears that more pediatric physician extenders will be employed in pediatric and neonatal ICUs in the future.

Chi-Square Distribution↗

Chemotactic peptide-induced cytoplasmic pH changes in incubated human monocytes.

Stimulation of phagocytic leukocytes with chemotactic factors results in transient acidification, followed by alkalinization of the cytosol. Human monocytes are known to alter their functional responses to the chemotactic peptide N-formylmethionyl-leucyl-phenylalanine (fMLP) in a complex fashion as they mature in vitro to macrophages. To examine the evolution of the cytoplasmic pH (pHi) response of monocytes to fMLP as they mature into macrophages, we incubated cells for 0, 24, 48, and 96 h (Medium-199 + 10% fetal bovine serum; 37 degrees C) and examined pHi using the fluorescent probe 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF; 1 microM) and a Perkin-Elmer 650/10 spectrofluorimeter (lambda em = 530 nm, lambda ex = 500, 450 nm) as previously described. The resting pHi of fresh (0 h) monocytes was 7.07 +/- 0.16 (SD) and was unchanged after incubation for 24, 48, or 96 h (7.09, 7.11, 7.05, respectively). Cells exhibited an fMLP dose-dependent cytoplasmic acidification, with maximal delta pHi occurring 30-60 s after exposure to 10(-7) M fMLP. The response to fMLP did not change with the duration of incubation and, as with neutrophils, cytoplasmic realkalinization was blocked by dimethylamiloride (20 microM). Incubation with 2-deoxyglucose (10 min, 5 mM), sufficient to inhibit by more than 90% the formyl peptide-stimulated superoxide generation by monocytes, slowed fMLP-induced acidification and abrogated the alkalinization. In addition, monocytes isolated from the blood of a patient with X-linked chronic granulomatous disease (CGD) underwent fMLP-induced acidification that was unmasked further by coincubation with dimethylamiloride, in a manner quantitatively similar to that of normal monocytes, despite the inability of the CGD cells to produce superoxide. The chemotactic factor-induced cytoplasmic pH responses of monocytes/macrophages remained constant as the cells matured in vitro and exhibited a dimethylamiloride-independent acidification and dependent alkalinization, as did the response in neutrophils. The cytoplasmic acidification of these cells thus did not correlate with the cells' production of superoxide and with the concomitant hexose monophosphate shunt activation, as has been suggested for other leukocyte types.

Calcium↗

Amniotic fluid volume: fluid dynamics and measurement technique.

Evaluation of amniotic fluid volume is an important aspect of obstetrical ultrasound. Several methods are currently used to describe amniotic fluid volumes. The most common are the subjective assessment of fluid and the semiquantitative methods. The reproducibility of these methods is excellent in experienced hands. Because of the multiple methods used to assess fluid, both oligohydramnios and polyhydramnios have numerous definitions. Regardless of which definition is used, it is clear that both of these entities are associated with a variety of fetal and maternal conditions. Abnormal amniotic fluid volume may be the only or earliest sonographic sign of an obstetrical problem. Therefore, it is important that sonologists are familiar with amniotic fluid volume assessment. Although subjective and semiquantitative techniques may produce similar results, a numerical scale is no substitute for experience and training. One should be able to recognize lesser degrees of fluid abnormality and be able to assess the trend of amniotic fluid volume in serial examinations.

Amniotic Fluid↗

Homeostatic balance between dorsal and cactus proteins in the Drosophila embryo.

The maternal-effect gene dorsal encodes the ventral morphogen that is essential for elaboration of ventral and ventrolateral fates in the Drosophila embryo. Dorsal belongs to the rel family of transcription factors and controls asymmetric expression of zygotic genes along the dorsoventral axis. The dorsal protein is cytoplasmic in early embryos, possibly because of a direct interaction with cactus. In response to a ventral signal, dorsal protein becomes partitioned into nuclei of cleavage-stage syncytial blastoderms such that the ventral nuclei have the maximum amount of dorsal protein, and the lateral and dorsal nuclei have progressively less protein. Here we show that transgenic flies containing the dorsal cDNA, which is driven by the constitutively active hsp83 promoter, exhibits rescue of the dorsal- phenotype. Transformed lines were used to increase the level of dorsal protein. Females with dorsal levels roughly twice that of wild-type produced normal embryos, while a higher level of dorsal protein resulted in phenotypes similar to those observed for loss-of-function cactus mutations. By manipulating the cactus gene dose, we found that in contrast to a dorsal/cactus ratio of 2.5 which resulted in fully penetrant weak ventralization, a cactus/dorsal ratio of 3.0 was acceptable by the system. By manipulating dorsal levels in different cactus and dorsal group mutant backgrounds, we found that the relative amounts of ventral signal to that of the dorsal-cactus complex is important for the elaboration of the normal dorsoventral pattern. We propose that in a wild-type embryo, the activities of dorsal and cactus are not independently regulated; excess cactus activity is deployed only if a higher level of dorsal protein is available. Based on these results we discuss how the ventral signal interacts with the dorsal-cactus complex, thus forming a gradient of nuclear dorsal protein.

Androgen-Binding Protein↗

An audit of induction of anaesthesia in neonates and small infants using pulse oximetry.

The frequency and severity of hypoxaemia during induction of anaesthesia in neonates and small infants at the Norfolk and Norwich Hospital, a district general hospital, was compared, using pulse oximetry, with that of the nearest specialist hospital, the Queen Elizabeth Hospital for Sick Children in London. There were differences in staffing and the choice of anaesthetic techniques between the hospitals. One third of the patients in both hospitals experienced desaturation of more than 5% (moderate or severe hypoxaemia) at one or more recordings during induction. The highest incidence of hypoxaemia was associated with awake intubation. There was no statistical difference in the incidence or severity of hypoxaemia between the hospitals. In the district general hospital, moderate or severe hypoxaemia of greater than 30 s duration was more likely if an anaesthetist with a regular paediatric operating list was not present at induction (p < 0.01).

Anesthesia, Inhalation↗