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Biomedical subjects

A Milner

Publications and source records attributed to A Milner.

At least 19 recordsLinked to original sources

Iron spin transition in Earth's mantle.

High-pressure Mössbauer spectroscopy on several compositions across the (Mg,Fe)O magnesiowüstite solid solution confirms that ferrous iron (Fe(2+)) undergoes a high-spin to low-spin transition at pressures and for compositions relevant to the bulk of the Earth's mantle. High-resolution x-ray diffraction measurements document a volume change of 4-5% across the pressure-induced spin transition, which is thus expected to cause seismological anomalies in the lower mantle. The spin transition can lead to dissociation of Fe-bearing phases such as magnesiowüstite, and it reveals an unexpected richness in mineral properties and phase equilibria for the Earth's deep interior.

Journal Article↗

Plethysmograph and interrupter resistance measurements in prematurely born young children.

BACKGROUND: Airways obstruction in premature infants is often assessed by plethysmography, which requires sedation. The interrupter (Rint) technique does not require sedation, but has rarely been examined in children under 2 years of age. OBJECTIVE: To compare Rint results with plethysmographic measurements of airway resistance (Raw) in prematurely born, young children. DESIGN: Prospective study. SETTING: Infant and Paediatric Lung Function Laboratories. PATIENTS: Thirty children with a median gestational age of 25-29 weeks and median postnatal age of 13 months. INTERVENTIONS AND MAIN OUTCOME MEASURES: The infants were sedated, airway resistance was measured by total body plethysmography (Raw), and Rint measurements were made using a MicroRint device. Further Raw and Rint measurements were made after salbutamol administration if the children remained asleep. RESULTS: Baseline measurements of Raw and Rint were obtained from 30 and 26 respectively of the children. Mean baseline Rint values were higher than mean baseline Raw results (3.45 v 2.84 kPa/l/s, p = 0.006). Limits of agreement for the mean difference between Rint and Raw were -1.52 to 2.74 kPa/l/s. Ten infants received salbutamol, after which the mean Rint result was 3.6 kPa/l/s and mean Raw was 3.1 kPa/l/s (limits of agreement -0.28 to 1.44 kPa/l/s). CONCLUSION: The poor agreement between Rint and Raw results suggests that Rint measurements cannot substitute for plethysmographic measurements in sedated prematurely born infants.

Airway Obstruction↗

Accuracy of the volume and pressure displays of high frequency oscillators.

OBJECTIVE: To determine the effect of frequency on the accuracy of volume and pressure displays of high frequency oscillators. METHODS: The effect of frequency on the displayed volume of the Stephanie, Dräger Babylog 8000 Plus, and SLE 5000 oscillators was assessed. A sine wave pump delivered a constant tidal volume at frequencies of 5-15 Hz to the patient manifold of the oscillators. The displayed volumes at each frequency were compared with the delivered volume. The effect of frequency on displayed pressure was assessed by connecting the oscillator's patient manifold to a lung model; three types of oscillator were studied (SensorMedics 3100A, SLE 5000, and Stephanie). Airway pressure was measured from the manifold using a pressure transducer and non-compliant tubing; the pressure measuring system had a flat frequency response to 30 Hz. RESULTS: The SLE 5000 volume display overread the delivered volume (by about 5%), but was not affected by frequency. At 5 Hz, the Dräger Babylog 8000 Plus and the Stephanie underread the delivered volume (by about 20%). Increasing frequency resulted in a greater discrepancy between the delivered and displayed volume with the Stephanie, but a smaller discrepancy with the Dräger Babylog 8000 Plus. Altering frequency had a small effect (maximum difference 6%) on the relation between the displayed and delivered pressure for all three oscillators. CONCLUSION: Frequency affects the accuracy of displayed volumes and, to a lesser extent, displayed pressures of high frequency oscillators. The results emphasise that data displayed by new devices should not be uncritically accepted.

Chronic Disease↗

The importance of ventilation to effective resuscitation in the term and preterm infant.

Although resuscitation at birth often has a successful outcome, there is very little data available on the optimal method. Face mask/bag resuscitation is relatively ineffective, rarely producing adequate alveolar ventilation before lung expansion has occurred, probably depending on the Head's Paradoxical Reflex to stimulate inspiratory efforts The T-piece/face mask technique is easier to use and more effective as the inflation pressure can be maintained for longer. Standard T-piece/endotracheal tube resuscitation produces inflation volumes of less than half of those generated by spontaneously breathing infants, and the functional residual capacity is not formed for several breaths. This can be overcome by maintaining the first inflation for 3 s. More studies are urgently required in very preterm infants as these are particularly vulnerable to volutrauma immediately after delivery.

Asphyxia Neonatorum↗

Serial fetal lung volume measurement using three-dimensional ultrasound.

OBJECTIVE: To establish reference intervals for fetal lung growth. DESIGN: Longitudinal observational study. SUBJECTS: Fifty-eight women with initially uncomplicated singleton pregnancies were recruited from the antenatal population of a teaching hospital. Four women were excluded from the final analysis because of complications arising in their pregnancy. METHODS: Each subject was serially scanned at monthly intervals. At each visit lung volume was measured using an ultrasound-based computerized three-dimensional imaging system. Multilevel models were used to determine conditional and unconditional reference intervals. RESULTS: Reference intervals for fetal lung growth were derived. Fetal lung volume increases in a non-linear way with gestation. CONCLUSIONS: Our computerized system has the capacity to be used in conjunction with any standard two-dimensional ultrasound scanner in order to measure volume. Lung volume measurement may be useful in predicting pulmonary hypoplasia.

Adult↗

International Guidelines for Neonatal Resuscitation: An excerpt from the Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care: International Consensus on Science. Contributors and Reviewers for the Neonatal Resuscitation Guidelines.

The International Guidelines 2000 Conference on Cardiopulmonary Resuscitation (CPR) and Emergency Cardiac Care (ECC) formulated new evidenced-based recommendations for neonatal resuscitation. These guidelines comprehensively update the last recommendations, published in 1992 after the Fifth National Conference on CPR and ECC. As a result of the evidence evaluation process, significant changes occurred in the recommended management routines for: * Meconium-stained amniotic fluid: If the newly born infant has absent or depressed respirations, heart rate <100 beats per minute (bpm), or poor muscle tone, direct tracheal suctioning should be performed to remove meconium from the airway. * Preventing heat loss: Hyperthermia should be avoided. * Oxygenation and ventilation: 100% oxygen is recommended for assisted ventilation; however, if supplemental oxygen is unavailable, positive-pressure ventilation should be initiated with room air. The laryngeal mask airway may serve as an effective alternative for establishing an airway if bag-mask ventilation is ineffective or attempts at intubation have failed. Exhaled CO(2) detection can be useful in the secondary confirmation of endotracheal intubation. * Chest compressions: Compressions should be administered if the heart rate is absent or remains <60 bpm despite adequate assisted ventilation for 30 seconds. The 2-thumb, encircling-hands method of chest compression is preferred, with a depth of compression one third the anterior-posterior diameter of the chest and sufficient to generate a palpable pulse. * Medications, volume expansion, and vascular access: Epinephrine in a dose of 0.01-0.03 mg/kg (0.1-0.3 mL/kg of 1:10,000 solution) should be administered if the heart rate remains <60 bpm after a minimum of 30 seconds of adequate ventilation and chest compressions. Emergency volume expansion may be accomplished with an isotonic crystalloid solution or O-negative red blood cells; albumin-containing solutions are no longer the fluid of choice for initial volume expansion. Intraosseous access can serve as an alternative route for medications/volume expansion if umbilical or other direct venous access is not readily available. * Noninitiation and discontinuation of resuscitation: There are circumstances (relating to gestational age, birth weight, known underlying condition, lack of response to interventions) in which noninitiation or discontinuation of resuscitation in the delivery room may be appropriate.

Blood Volume↗

The isolation and detection of non-collagenous proteins from the compact bone of the dinosaur Iguanodon.

This report describes the isolation of guanidinium chloride extractable protein from demineralised bone extracts obtained from the 125-130 mya dinosaur Iguanodon. Protein products were isolated in the Mr. range 5,000-66,000 using SDS-PAGE and represent the first electrophoretically defined proteins isolated from dinosaur tissues. The levels of glycine, aspartate and serine tentatively suggest the presence of phosphoproteins. Hydroxylysine and hydroxyproline were not detected, confirming the presence of non-collagenous material. In addition the absence of ornithine confirmed lack of bacterial contamination. The relatively high level of leucine in the 2MNaCl NaCl fractions together with the abolition of alcian blue reactivity following protease-free chondroitinase digestion suggests the presence of proteoglycans. The study is of interest in describing the early proteins laid down in mineralised tissues for epitactic crystal growth and may provide evidence on evolutionary aspects of bone proteins.

Animals↗

Chromosomal instability in haemopoietic cells of the foetus, mother and offspring after in utero irradiation of the CBA/Ca mouse.

PURPOSE: The present study was conducted to test the susceptibility of the mouse foetus to transmit chromosomal instability to the haemopoietic stem cells of offspring after in utero X-or plutonium-239-irradiation. MATERIALS AND METHODS: Pregnant CBA/Ca-mice were injected with 80 kBq/kg 239Pu or X-irradiated with 1 Gy X-rays on days 13 or 14 of gestation. CFU-A cultures were grown from haemopoietic stem cells sampled from foetal liver and the bone marrow from the offspring and from the mother. Non-clonal, unstable chromosomal aberrations were scored in metaphases from individual stem cell colonies. RESULTS: The relative excess (RE) of unstable chromosomal aberrations in foetal liver cells irradiated with 1 Gy X-rays increased from 1.6 at day 2 up to 2.7 at day 4 after irradiation. In the bone marrow cells from the mother, this value was 1.8 (average from cells sampled at days 3 and 14 after irradiation). After injection of the pregnant mice with 235Pu, the yield of unstable chromosomal aberrations per cell was 0.14+/-0.03 (RE approximately 10) in descendants of bone marrow cells from the mother, 0.11+/-0.02 (RE = 10) in descendants of foetal liver cells and 0.16+/-0.05 (RE = 10) in descendants of bone marrow cells from the offspring. CONCLUSIONS: From the numerical analysis of non-clonal, unstable aberrations in haemopoietic cells from the foetus, the mother and the offspring after in utero irradiation, it was concluded that in utero irradiation of the CBA/Ca mouse was not more efficient in inducing chromosomal instability in the offspring than in the foetus or the mother. All three cell populations exhibited a similar degree of unstable aberrations, both in terms of the absolute numbers of non-clonal aberrations and in terms of relative excess compared with unexposed controls.

Animals↗

Pharmacokinetics of three doses of epidural ropivacaine during hysterectomy and comparison with bupivacaine.

PURPOSE: Ropivacaine is a new long-acting aminoamide local anaesthetic, structurally related to bupivacaine. The clinical efficacy of 125 mg, 187.5 mg and 250 mg ropivacaine have been reported and compared with 125 mg bupivacaine for epidural analgesia during hysterectomy. In the pharmacokinetic part of this study the objectives were to 1) determine the dose proportionality in the pharmacokinetics of epidural ropivacaine, and 2) compare the pharmacokinetics of 125 mg ropivacaine and 125 mg bupivacaine. METHODS: In a randomized, double-blind controlled study, patients received one of four treatment regimens with ropivacaine (125, 187.5 or 250 mg) or bupivacaine (125 mg) as a 25 ml epidural bolus administered over three minutes. Peripheral venous blood samples were collected over 24 hr for ropivacaine or bupivacaine quantification using gas chromatography with nitrogen sensitive detection. Pharmacokinetic variables were derived from plasma concentration-time curve data. RESULTS: Fifty two women entered the study. Demographic characteristics were similar among groups. Six patients were excluded due to inadequate sensory block or an insufficient number of plasma samples. The peak plasma concentration (Cmax) of ropivacaine and the total area under the plasma concentration-time curve (AUC) increased proportionally with the dose. Apparent plasma clearance (CL) and the terminal half-life (t1/2) were similar in the three ropivacaine groups. When compared with the 125 mg ropivacaine group, the bupivacaine group had a longer terminal half life (P < 0.05). CONCLUSIONS: Epidural ropivacaine displays dose-proportional pharmacokinetic behaviour for doses of 125 mg to 250 mg. Ropivacaine has a shorter terminal half-life than bupivacaine.

Adult↗

Apoptosis-specific protein (ASP) identified in apoptotic Xenopus thymus tumor cells.

A novel apoptosis-specific protein (ASP) has recently been identified in the cytoplasm of apoptotic mammalian cells. This paper investigates whether ASP is found in Xenopus thymus tumor-derived lymphoid cell lines undergoing apoptosis and also in apoptotic, nontransformed splenocytes. Cultured Xenopus tumor lymphoid cells induced to undergo apoptosis by serum deprivation or treatment with the calcium ionophore, ionomycin, displayed altered morphology typical of apoptotic cells, as judged by flow cytometric light-scatter characteristics and by fluorescence microscopy of acridine-orange-stained cells. Flow cytometry of permeabilized cells and fluorescence microscopy of acetone-fixed cytospins revealed that apoptotic Xenopus tumor cells, especially those displaying loss or condensation of DNA, displayed increased expression of epitopes recognized by a rabbit polyclonal antibody against ASP. Flow cytometry confirmed that ASP is also expressed in splenocytes induced to apoptose by culture in ionomycin or following concanavalin A stimulation. No increased expression of ASP was seen when lymphoid tumor cells or splenocytes were induced into necrosis by overdose with the antifungal agent amphotericin B. Western blotting with antibody against ASP identified the emergence of several protein bands in cell lysates from apoptotic, but not necrotic, Xenopus tumor cells. The new and simple methodology for identifying apoptotic cells described here is likely to be of value to those studying immune system development and associated programmed cell death in Xenopus.

Amphotericin B↗

Volume estimation from multiplanar 2D ultrasound images using a remote electromagnetic position and orientation sensor.

A system is described for calculating volume from a sequence of multiplanar 2D ultrasound images. Ultrasound images are captured using a video digitising card (Hauppauge Win/TV card) installed in a personal computer, and regions of interest transformed into 3D space using position and orientation data obtained from an electromagnetic device (Polhemus, Fastrak). The accuracy of the system was assessed by scanning 10 water filled balloons (13-141 mL), 10 kidneys (147-200 mL) and 16 fetal livers (8-37 mL) in water using an Acuson 128XP/10 (5 MHz curvilinear probe). Volume was calculated using the ellipsoid, planimetry, tetrahedral and ray tracing methods and compared with the actual volume measured by weighing (balloons) and water displacement (kidneys and livers). The mean percentage error for the ray tracing method was 0.9 +/- 2.4%, 2.7 +/- 2.3%, 6.6 +/- 5.4% for balloons, kidneys and livers, respectively. So far the system has been used clinically to scan fetal livers and lungs, neonate brain ventricles and adult prostate glands.

Algorithms↗

[Role of anticholinergic agents in acute bronchiolitis in infants].

There is almost universal agreement that neither beta 2-agonists, theophyllin nor steroids, given either by inhalation or systemically, have any effect on lung function in acute bronchiolitis of infancy. As ipratropium bromide appears to be a more effective bronchodilator drug than beta 2-stimulants in the first year of life, a study was set up to investigate its possible role in bronchiolitis. Diagnostic requirements for inclusion in the study were tachypnoea, hyperinflation recession, and the presence of fine crepitations on auscultation with a chest X-ray which excluded either heart failure or gross pneumonia. Twenty-five infants were recruited in the preliminary study. A respiratory jacket and water filled oesophageal catheter (feeding tube) were used to measure the work of breathing per minute and per litre of expired gases. After baseline readings the infants received salbutamol (2.5 mg), ipratropium bromide (250 micrograms) or placebo in 2 ml volumes using a standard nebuliser. The salbutamol and water were associated with an increase in the work of breathing of 4% and 22% respectively. The ipratropium therapy led to a fall of 18% with a significant response in 6 of 15 infants studied. Following these encouraging results, a double blind study was set up assessing the effects of nebulised ipratropium bromide (250 micrograms) and nebulised saline given every 6 hours to 66 infants admitted to the ward with acute bronchiolitis. Response to therapy was determined using symptom scores and need for nebulised therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Structure of the C3HC4 domain by 1H-nuclear magnetic resonance spectroscopy. A new structural class of zinc-finger.

A recently identified sequence motif, referred to as "C3HC4" (also "RING finger" and "A Box") for its distinctive pattern of putative metal-binding residues, has been found in a wide range of proteins. In a previous paper we described the expression and purification of fragments encompassing this motif from the Vmw110 (IPC0) protein family. We showed that the equine herpes virus protein binds zinc ions and adopts a beta beta alpha beta fold. We now report the tertiary structure of this domain in solution, as determined by two-dimensional 1H-NMR An amphipathic alpha-helix lies along one surface of a triple-stranded beta-sheet. Four pairs of metal-binding residues sequester two zincs at distinct tetrahedral sites. The first and third pairs bind one metal ion, while the second and fourth pairs bind the other, forming an interleaved whole. The first and the fourth pairs are contained within two prominent, well-defined loops related by an approximate dyad symmetry. Conserved residues within the helix, sheet and loops contribute to a compact hydrophobic core. The region comprising the first two beta-strands and the alpha-helix has remarkable structural similarity with a TFIIIA type of zinc finger, even though the C3HC4 domain appears not to bind specifically to DNA or RNA. Using site-directed mutagenesis we demonstrate that exposed polar side-chains of the C3HC4 alpha-helix are essential for trans-activation of gene expression by an intact herpes virus regulatory protein.

Amino Acid Sequence↗

A novel arrangement of zinc-binding residues and secondary structure in the C3HC4 motif of an alpha herpes virus protein family.

A highly conserved, cysteine-rich region plays a crucial role in the function of a family of regulatory proteins encoded by alpha herpes viruses. The so-called C3HC4 motif spans approximately 60 residues and has been predicted to bind zinc. This motif occurs in a number of other viral and cellular proteins, many of which appear to be involved in some aspect of the regulation of gene expression. We have cloned and expressed in bacteria a portion of immediate-early protein Vmw110 of herpes simplex virus type 1 that encompasses the C3HC4 motif, and the equivalent regions from the homologous proteins of varicella zoster virus and equine herpes virus type 1 (EHV-1). All three polypeptides were purified and found to bind zinc stably. None of the three interacted significantly with either DNA or RNA under our assay conditions. The EHV-1 domain yielded interpretable proton nuclear magnetic resonance spectra. Assignment of resonances and analysis of nuclear Overhauser effects revealed its secondary structure. Starting from the N terminus, this consists of an ordered but irregular loop, the first two strands of a triple-stranded antiparallel beta-sheet, two turns of an alpha-helix, a second irregular loop, and the third strand of the beta-sheet. It appears that, taking the cysteine and histidine residues in turn, cysteine residues I, II, IV and V co-ordinate one zinc atom while the histidine residue and cysteine residues III, VI and VII co-ordinate a second zinc atom. This arrangement of secondary structure differs from that found in other characterized zinc-containing proteins.

Amino Acid Sequence↗

Irradiated fibroblasts protect Burkitt lymphoma cells from apoptosis by a mechanism independent of bcl-2.

When cells of fresh Burkitt lymphoma (BL) biopsies are explanted into tissue culture, their survival and growth are greatly dependent on the presence of a feeder layer of irradiated fibroblasts. To investigate the nature of this feeder dependence, we characterized the growth requirements of a panel of Epstein-Barr Virus (EBV)-negative and -positive BL cell lines in both the absence and the presence of feeder cells in vitro. Four EBV-negative BL lines and 4 EBV-positive lines displaying the phenotype of BL cells in vivo required high cell density for proliferation in the absence of feeder cells, but grew out as single-cell clones when seeded on irradiated human fibroblasts. EBV-positive BL cell lines which had acquired an activated phenotype similar to that of lymphoblastoid cell lines required much lower cell densities for autonomous proliferation. The EBV-negative Burkitt lymphoma line BL70 was used as a model to study the feeder-cell dependence in more detail. BL70 cells grew in the absence of feeder cells only at high cell density and at high FCS concentration. In the presence of feeder cells, BL70 cells became clonogenic even at greatly reduced FCS concentration. A decrease in either cell density or FCS concentration induced apoptosis. Supernatants from feeder cells and from BL70 cells growing autonomously at high cell density were unable to substitute for the survival and growth-promoting effect of the feeder cells. Protection of Burkitt lymphoma cells from apoptosis by co-cultivation with irradiated fibroblasts was not mediated by induction of bcl-2.(ABSTRACT TRUNCATED AT 250 WORDS)

Apoptosis↗