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L Brennan

Publications and source records attributed to L Brennan.

At least 19 recordsLinked to original sources
PubMed1995

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1993

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↗
PubMed1992

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↗
PubMed1992

University neonatal centers and level II centers compatibility. Jacksonville experience.

Reported are 10 years experience in the development of a Citywide Neonatal Program in the Jacksonville area, which could be helpful as a model for establishing relationships between academic centers and outside Level II nurseries. The four phases of development are documented. An analysis of the financial impact to the academic program is presented and also an outline of the gain realized by the Department of Pediatrics, University of Florida Health Science Center. The positive results in amalgamation of the neonatal services in Jacksonville have far outweighed any potential harmful effects from competition between an academic center and other private nurseries in the city.

Academic Medical Centers↗
PubMed1991

Affinity-chromatographic purification of sixteen cysteine-substituted maltoporin variants: thiol reactivity and cross-linking in an outer membrane protein of Escherichia coli.

Wild-type and 16 variant maltoporins with site-directed cysteine substitutions at 14 sites were purified by a novel one-step affinity-chromatographic procedure. The trimer stability of purified proteins with C22S, C38S and G103C substitutions was reduced compared to wild-type maltoporin. Quantitative labelling with N-ethyl[14C]maleimide, cross-linking with bifunctional bismaleimides and disulphide formation was used to test the reactivity of cysteines in the folded protein. The maleimide reactivity of the residues was in the order: 152 approximately equal to 153 greater than 265 greater than 30 approximately equal to 103 approximately equal to 120 approximately equal to 154 approximately equal to 382 greater than 57 approximately equal to 146, with the other sites (22, 38, 97, 184) poorly labelled. Only cysteines at 152 or 153 permitted the formation of inter-subunit disulphide bonds suggesting these residues are located within 0.5-0.9 nm of each other in homotrimers of maltoporin. S152C and S153C as well as S154C permitted the formation of inter-subunit cross-links using bifunctional bismaleimides. The cross-linkability and the high reactivity to N-ethylmaleimide of the 150 region was consistent with the current model of the structure of maltoporin in the outer membrane; the reactivity of the other sites is also discussed within the context of this model.

Amino Acid Sequence↗
PubMed1991

Genetic mapping of starch- and lambda-receptor sites in maltoporin: identification of substitutions causing direct and indirect effects on binding sites by cysteine mutagenesis.

Cysteine mutagenesis was used to test the proximity of 16 residues to protein-ligand interaction sites in maltoporin (LamB protein). LamB protein with additional cysteines was incorporated into the outer membrane of Escherichia coli except with a Ser-30----Cys substitution. Phage Lambda and starch binding was assayed before and after incubation of mutants with six thiol-specific reagents. Four categories of mutation were recognized on the basis of phenotype and modification for each of the Lambda- and starch binding sites. The thiol modification experiments helped to clarify whether the phenotype of a mutation was due to a substitution at the binding site or an indirect perturbation of the structure. This study suggests that the cysteine mutagenesis/thiol modification approach may be usefully applied to the operational mapping of surface-accessible binding sites or epitopes.

Bacterial Outer Membrane Proteins↗
PubMed1990

Simultaneous flow cytometric measurements of cytoplasmic Ca++ and membrane potential changes upon FMLP exposure as HL-60 cells mature into granulocytes: using [Ca++]in as an indicator of granulocyte maturity.

Treatment of human leukemic HL-60 cells with N,N-dimethylformamide (DMF) induces them to mature until they reach granulocytoid morphology 3-6 d later. We have reported a maturation-dependent ability of these cells to respond to phorbol myristate acetate (PMA), as evaluated by membrane depolarization and by oxidative burst product formation (Newburger et al.: J. Biol. Chem. 259,3771, 1984). More recently we have attempted to develop techniques for simultaneous evaluation of these parameters during HL-60 cell maturation. Here, we compare the cytoplasmic [Ca++] and membrane potential changes elicited by the chemotactic peptide fMLP via simultaneous measurement of individual cells in a fluorescence-activated cell sorter (FACS), as done previously for mature granulocytes (Lazzari et al.: J. Biol. Chem. 261,9710, 1986). The stimulus-induced [Ca++]in changes are detected with the fluorescent probe Indo-1 and reproducibly increase in magnitude for a subpopulation of cells as the cells mature into granulocytes. Ca++ responsiveness to formyl peptide is restricted to a subpopulation of HL-60 granulocytes which expresses receptors for chemotactic peptide and consistently increases in magnitude (in response to the same concentration of agonist) with maturation. In contrast, there is less consistency in the direction or magnitude of membrane potential changes elicited under the same circumstances from the same maturing HL-60 cells.

Calcium↗
PubMed1989

Surgical glove failure rate.

Surgical gloves were collected after day-time operations for a 4-week period. Glove punctures were located by inflating each glove with compressed air and immersing the inflated glove in water. During the period of the study 681 surgical operations were performed. A total of 3790 gloves was collected, 334 gloves (8.8%) had perforations at the end of the surgical procedure. Defects occurred in one or more gloves in 32.0% of all operations.

Equipment Failure↗
PubMed1987

Spectrum and mode of action of azithromycin (CP-62,993), a new 15-membered-ring macrolide with improved potency against gram-negative organisms.

The macrolide antibiotic azithromycin (CP-62,993; 9-deoxo-9a-methyl-9a-aza-9a-homoerythromycin A; also designated XZ-450 [Pliva Pharmaceuticals, Zagreb, Yugoslavia]) showed a significant improvement in potency against gram-negative organisms compared with erythromycin while retaining the classic erythromycin spectrum. It was up to four times more potent than erythromycin against Haemophilus influenzae and Neisseria gonorrhoeae and twofold more potent against Branhamella catarrhalis, Campylobacter species, and Legionella species. It had activity similar to that of erythromycin against Chlamydia spp. Azithromycin was significantly more potent versus many genera of the family Enterobacteriaceae; its MIC for 90% of strains of Escherichia, Salmonella, Shigella, and Yersinia was less than or equal to 4 micrograms/ml, compared with 16 to 128 micrograms/ml for erythromycin. Azithromycin inhibited the majority of gram-positive organisms at less than or equal to 1 micrograms/ml. It displayed cross-resistance to erythromycin-resistant Staphylococcus and Streptococcus isolates. It had moderate activity against Bacteroides fragilis and was comparable to erythromycin against other anaerobic species. Azithromycin also demonstrated improved bactericidal activity in comparison with erythromycin. The mechanism of action of azithromycin was similar to that of erythromycin since azithromycin competed effectively for [14C]erythromycin ribosomebinding sites.

Anti-Bacterial Agents↗
PubMed1986

Educating Martha.

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Child, Preschool↗