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Biomedical subjects

D Chamberlain

Publications and source records attributed to D Chamberlain.

At least 19 recordsLinked to original sources

European Resuscitation Council Guidelines 2000 for Adult Advanced Life Support. A statement from the Advanced Life Support Working Group(1) and approved by the Executive Committee of the European Resuscitation Council.

The European Resuscitation Council (ERC) last issued guidelines for Basic Life Support (BLS) in 1998 [1]. These were based on the 1997 International Liaison Committee on Resuscitation (ILCOR) Advisory Statements [2]. In 1999 and 2000 representatives of ILCOR, at the invitation of the American Heart Association, met on a number of occasions in Dallas to agree a Consensus on Science upon which future guidelines would be based. Representatives from the ERC played a prominent role in the deliberations, which culminated in the publication of "Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care--A Consensus on Science" in August 2000 [3]. The consensus was evidence-based wherever possible. The ERC ALS Working Group has considered this document and has recommended some changes in the guidelines that will be suitable for European practice. These changes, together with a summary of the Sequence of Actions in ALS, are presented in this paper.

Adult↗

Optimal Response to Cardiac Arrest study: defibrillation waveform effects.

INTRODUCTION: Advances in early defibrillation access, key to the "Chain of Survival", will depend on innovations in defibrillation waveforms, because of their impact on device size and weight. This study compared standard monophasic waveform automatic external defibrillators (AEDs) to an innovative biphasic waveform AED. MATERIAL AND METHODS: Impedance-compensated biphasic truncated exponential (ICBTE) and either monophasic truncated exponential (MTE) or monophasic damped sine (MDS) AEDs were prospectively, randomly assigned by date in four emergency medical services. The study design compared ICBTE with MTE and MDS combined. This subset analysis distinguishes between the two classes of monophasic waveform, MTE and MDS, and compares their performance to each other and to the biphasic waveform, contingent on significant overall effects (ICBTE vs. MTE vs. MDS). Primary endpoint: Defibrillation efficacy with < or =3 shocks. Secondary endpoints: shock efficacy with < or =1 shock, < or =2 shocks, and survival to hospital admission and discharge. Observations included return of spontaneous circulation (ROSC), refibrillation, and time to first shock and to first successful shock. RESULTS: Of 338 out-of-hospital cardiac arrests, 115 had a cardiac aetiology, presented with ventricular fibrillation, and were shocked by an AED. Defibrillation efficacy for the first "stack" of up to 3 shocks, for up to 2 shocks and for the first shock alone was superior for the ICBTE waveform than for either the MTE or the MDS waveform, while there was no difference between the efficacy of MTE and MDS. Time from the beginning of analysis by the AED to the first shock and to the first successful shock was also superior for the ICBTE devices compared to either the MTE or the MDS devices, while again there was no difference between the MTE and MDS devices. More ICBTE patients achieved ROSC pre-hospital than did MTE patients. While the rates of ROSC were identical for MTE and MDS patients, the difference between ICBTE and MDS was not significant. Rates of refibrillation and survival to hospital admission and discharge did not differ among the three populations. CONCLUSIONS: ICBTE was superior to MTE and MDS in defibrillation efficacy and speed and to MTE in ROSC. MTE and MDS did not differ in efficacy. There were no differences among the waveforms in refibrillation or survival.

Adult↗

Randomised controlled trials of staged teaching for basic life support: 2. Comparison of CPR performance and skill retention using either staged instruction or conventional training.

Teaching CPR in stages is a strategy designed to improve skill acquisition and retention. This method has been compared with conventional teaching in a randomised trial involving 495 volunteers. The first ('bronze') stage was simplified by omitting ventilation and giving compressions in sets of 50 with pauses to open the victim's airway; in the second ('silver') stage ventilation was introduced in a ratio of 50 compressions to five breaths, and in the third ('gold') stage, the volunteers were converted to conventional CPR. 51% of those taught by this method reattended for the second ('silver') stage compared with 25% who were taught conventional CPR and advised to return for a revision session. 38% of the staged group reattended for the third ('gold') compared with 8% for the conventional group. Modest improvement in skill acquisition has earlier been reported for the 'bronze' stage teaching, and this has been followed by better performance in some of the components tested after the subsequent stages. Comparisons after the 'gold' stage were limited by the small numbers who reattended for a third session of conventional training, but no special difficulties were noted in changing the ratio of compressions to ventilation that was necessary to convert the staged training volunteers to conventional CPR. The increased number of compressions that can be achieved by teaching 'bronze' stage CPR with no ventilation was retained, to a lesser degree, when the 'silver' ratio of 50 compressions to five breaths was compared with the conventional 15:2 ratio. Our observations suggest that during the first critical 8 min of a resuscitation attempt, 58% more compressions might be delivered by using the 50:5 ratio - an increase that is likely to result in a significant augmentation of blood flow with important clinical implications. More comparative information will become available when the results of unannounced home testing are analysed.

Adult↗

Improved functional recovery of denervated skeletal muscle after temporary sensory nerve innervation.

Prolonged muscle denervation results in poor functional recovery after nerve repair. The possible protective effect of temporary sensory innervation of denervated muscle, prior to motor nerve repair, has been examined in the rat. Soleus and gastrocnemius muscles were denervated by cutting the tibial nerve, and the peroneal nerve was then sutured to the transected distal tibial nerve stump either immediately or after two, four or six months. In half of the animals with delayed repair, the saphenous (sensory) nerve was temporarily attached to the distal nerve stump. Muscles were evaluated three months after the peroneal-to-tibial union, and were compared with each other, with unoperated control muscles and with untreated denervated muscles. After four to six months of sensory "protection", gastrocnemius muscles weighed significantly more than unprotected muscles, and both gastrocnemius and soleus muscles exhibited better preservation of their structure, with less fiber atrophy and connective tissue hyperplasia. The maximum compound action potentials were significantly larger in gastrocnemius and soleus muscles following sensory protection, irrespective of the delay in motor nerve union. Isometric force, although less than in control animals and in those with immediate nerve repair, remained reasonably constant after sensory protection, while in unprotected muscles there was a progressive and significant decline as the period of denervation lengthened. We interpret these results as showing that, although incapable of forming excitable neuromuscular junctions, sensory nerves can nevertheless exert powerful trophic effects on denervated muscle fibers. We propose that these findings indicate a useful strategy for improving the outcome of peripheral nerve surgery.

Animals↗

The speech-language pathologist's role in a writing lab approach.

In a writing lab approach, speech-language pathologists (SLPs) work on collaborative teams with general and special educators to foster language growth using inclusive, curriculum-based, computer-supported writing process instruction. By engaging students in authentic writing projects using recursive writing processes--planning, organizing, drafting, revising, editing, publishing, presenting--and supporting them with instructional scaffolding, peer feedback, and computers, SLPs can address individualized needs while achieving goals of the general education curriculum. Case examples illustrate how intervention can be designed to meet the needs of students with diverse disabilities to interact socially and progress academically within the general education curriculum.

Computer-Assisted Instruction↗

Multicenter, randomized, controlled trial of 150-J biphasic shocks compared with 200- to 360-J monophasic shocks in the resuscitation of out-of-hospital cardiac arrest victims. Optimized Response to Cardiac Arrest (ORCA) Investigators.

BACKGROUND: In the present study, we compared an automatic external defibrillator (AED) that delivers 150-J biphasic shocks with traditional high-energy (200- to 360-J) monophasic AEDs. METHODS AND RESULTS: AEDs were prospectively randomized according to defibrillation waveform on a daily basis in 4 emergency medical services systems. Defibrillation efficacy, survival to hospital admission and discharge, return of spontaneous circulation, and neurological status at discharge (cerebral performance category) were compared. Of 338 patients with out-of-hospital cardiac arrest, 115 had a cardiac etiology, presented with ventricular fibrillation, and were shocked with an AED. The time from the emergency call to the first shock was 8.9+/-3.0 (mean+/-SD) minutes. CONCLUSIONS: The 150-J biphasic waveform defibrillated at higher rates, resulting in more patients who achieved a return of spontaneous circulation. Although survival rates to hospital admission and discharge did not differ, discharged patients who had been resuscitated with biphasic shocks were more likely to have good cerebral performance.

Adult↗

Randomised controlled trials of staged teaching for basic life support. 1. Skill acquisition at bronze stage.

We have investigated a method of teaching community CPR in three stages instead of in a single session. These have been designated bronze, silver, and gold stages. The first involves only opening of the airway and chest compression with back blows for choking, the second adds ventilation in a ratio of compressions to breaths of 50:5, and the third is a conversion to conventional CPR. In a controlled randomised trial of 495 trainees we compared the performance in tests immediately after instruction of those who had received a conventional course and those who had had the simpler bronze level tuition. The tests were based on video recordings of simulated resuscitation scenarios and the readouts from recording manikins. Differences occurred as a direct consequence of ventilation being required in one group and not the other, some variation probably followed from unforeseen minor changes in the way that instruction was given, whilst others may have followed from the greater simplicity in the new method of training. A careful approach was followed by slightly more trainees in the conventional group whilst appreciably more in the bronze group remembered to shout for help (44% vs. 71%). A clear advantage was also seen for bronze level training in terms of those who opened the airway as taught (35% vs. 56%), for checking breathing (66% vs. 88%), and for mentioning the need to phone for an ambulance (21% vs. 32%). Little difference was observed in correct or acceptable hand position between the conventional group who were given detailed guidance and the bronze group who were instructed only to push on the centre of the chest. The biggest differences related to the number of compressions given. The mean delay to first compression was 63 s and 34 s, and the mean duration of pauses between compressions was 16 s and 9 s, respectively. Average performed rates were similar in the two groups, but more in the conventional group compressed too slowly whereas more in the bronze group compressed too rapidly. Observations were made for only three cycles of compression, but extrapolating these to the 8 min often considered a watershed for chances of survival for victims of cardiac arrest, an average of 308 compressions would be expected from those using conventional CPR compared with 675 for those using bronze level CPR. The implications of this difference are discussed.

Adult↗

Hearing conservation for farmers: source apportionment of occupational and environmental factors contributing to hearing loss.

Those who work on farms continue to have a strikingly high prevalence of hearing loss, despite efforts to promote hearing conservation in agriculture. To develop improved hearing conservation programs, we performed a source apportionment analysis for hearing loss in a large, multiphasic health survey, the New York Farm Family Health and Hazard Survey. We used information from audiometric, otoscopic, and tympanometric examinations; detailed general health and farm exposure interviews; and a second interview that focused on additional potential determinants of hearing loss. Hearing loss on audiometry was significantly associated with increased age, male gender, education through high school or less, lifetime years of hunting with guns, lifetime years of use of a grain dryer, and a history of spraying crops during the previous year. Hearing conservation programs for farmers should thus be directed toward reduction in noise exposure, both from occupational and non-occupational sources. Additional study is needed to evaluate the association seen between crop spraying and hearing loss.

Adult↗

Correlation of chest radiographic findings with biopsy-proven acute lung rejection.

The purpose of this study was to determine the chest radiographic findings of acute rejection and the accuracy of chest radiography in making this diagnosis in patients undergoing lung transplantation. For each of 100 transbronchial biopsies performed on 25 lung transplant recipients (single lung in three, double lung in 22), chest radiographs obtained within 24 hours before the biopsy were reviewed retrospectively without knowledge of clinical or biopsy information. Transbronchial biopsy revealed 42 instances of acute rejection in 17 patients and 58 instances of no acute rejection (normal, n = 43; other processes, n = 15). All pulmonary parenchymal radiographic abnormalities were assessed. Acute rejection was associated with the presence of middle or lower lung reticular interstitial or airspace disease in 21 lungs (sensitivity = 0.50 [21/42]). This pattern was seen in 18 lungs without acute rejection (specificity = 0.69 [40/58]). There was no difference in the appearance of the lungs between grades 1 and 2 acute rejection. Normal lungs were noted in 20 instances of acute rejection (48%). The authors conclude that chest radiograph findings are abnormal in about 50% of instances of biopsy-proven acute rejection. Because the appearance of acute rejection is similar to that of other conditions, the diagnosis cannot be made accurately by chest radiography.

Acute Disease↗

Upregulation of T-helper 1 cytokines and chemokine expression in post-transplant airway obliteration.

The major obstacle to long-term survival after lung transplantation is chronic graft dysfunction manifest as bronchiolitis obliterans. Since the early stages are characterized by proliferation of itinerant cells (lymphocytes and macrophages), we hypothesized that cytokines and chemokines may play a role in the development of the fibroproliferative process. In a heterotopic rat tracheal transplant model, we studied isografts and allografts 3, 7, and 21 d after transplantation as representative time points for the triphasic time course in the evolution of allograft airway obliteration. Using a semiquantitative RT-PCR technique, intragraft gene expression of T-helper 1 (Th1)- and Th2-type cytokines and of C-C and C-X-C chemokines was examined. The results of our study show a distinct pattern of cytokine and chemokine gene expression in the development of post-transplant airway obliteration. Allografts, in contrast to isografts, showed a strong and persistent Th1-type response (expression of interleukin-2 and interferon-gamma genes), even after fibrous airway obliteration was complete, suggesting an ongoing allo-immune process until late in the fibroproliferative stage. RANTES and MCP-1 were also upregulated late after transplantation, whereas MIP-2 upregulation occurred early post-transplant and was not restricted to allografts alone, which might reflect alloantigen-independent processes after transplantation that are present in both allografts and isografts.

Animals↗

Expression and prognostic significance of metalloproteinases and their tissue inhibitors in patients with small-cell lung cancer.

PURPOSE: Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are important in tumor development and progression. MMP expression has been correlated with advanced clinical stage and poor survival in some tumors, but data for small-cell lung cancer (SCLC) are lacking. The aim of this study was to assess the expression of MMPs and TIMPs in SCLC and to evaluate their importance relative to standard prognostic factors. PATIENTS AND METHODS: Expression of MMP-1, -2, -3, -9, -11, -13, and -14 and TIMP-1, -2, -3, and -4 was evaluated by immunohistochemistry (IHC). In situ hybridization was used to confirm expression of specific mRNAs. Clinical data collected included sex, tumor stage, performance status, weight loss, hematology (hemoglobin, WBC, platelets) and biochemistry (sodium, albumin, alkaline phosphatase, lactate dehydrogenase), treatment, and survival. RESULTS: Samples from 46 patients were evaluated: 30 males, 16 females; 29 limited, 17 extensive stage; 35 Eastern Cooperative Oncology Group performance status 0-1. Positive IHC staining was evident for MMP-1 and -9 in 60% to 70% of tumor cells, and for MMP-11, -13, and -14 and TIMP-2 and -3 in 70% to 100% of tumor cells. Stromal staining of TIMP-1 to -3 was present in less than 30% of specimens. On multivariate analysis, only stage and decreased tumoral expression of TIMP-1 were significant for response (P =.043). Significant factors for survival were tumor stage (P =.0021); weight loss (P =. 013); and high tumor cell expression of MMP-3 (P =.077), MMP-11 (P =. 031), and MMP-14 (P =.019). MMP and TIMP expression did not differ significantly between stages. CONCLUSION: MMPs and TIMPs are widely expressed in SCLC. Increased tumoral expression of MMP-3, -11, and -14 were independent negative prognostic factors for survival. The results support the evaluation of synthetic MMP inhibitors in patients with SCLC.

Carcinoma, Small Cell↗

A synthetic holliday junction is sandwiched between two tetrameric Mycobacterium leprae RuvA structures in solution: new insights from neutron scattering contrast variation and modelling.

The interaction between homologous DNA molecules in recombination and DNA repair leads to the formation of crossover intermediates known as Holliday junctions. Their enzymatic processing by the RuvABC system in bacteria involves the formation of a complex between RuvA and the Holliday junction. To study the solution structure of this complex, contrast variation by neutron scattering was applied to Mycobacterium leprae RuvA (MleRuvA), a synthetic analogue of a Holliday junction with 16 base-pairs in each arm, and their stable complex. Unbound MleRuvA was octameric in solution, and formed an octameric complex with the DNA junction. The radii of gyration at infinite contrast were determined to be 3.65 nm, 2.74 nm and 4.15 nm for MleRuvA, DNA junction and their complex, respectively, showing that the complex was structurally more extended than MleRuvA. No difference was observed in the presence or absence of Mg2+. The large difference in RG values for the free and complexed protein in 65% 2H2O, where the DNA component is "invisible", showed that a substantial structural change had occurred in complexed MleRuvA. The slopes of the Stuhrmann plots for MleRuvA and the complex were 19 and 15 or less (x10(-5)), respectively, indicating that DNA passed through the centre of the complex. Automated constrained molecular modelling based on the Escherichia coli RuvA crystal structure demonstrated that the scattering curve of octameric MleRuvA in 65% and 100% 2H2O is explained by a face-to-face association of two MleRuvA tetramers stabilised by salt-bridges. The corresponding modelling of the complex in 65% 2H2O showed that the two tetramers are separated by a void space of about 1-2 nm, which can accommodate the width of B-form DNA. Minor conformational changes between unbound and complexed MleRuvA may occur. These observations show that RuvA plays a more complex role in homologous recombination than previously thought.

Amino Acid Sequence↗

Possible arrangement of the five domains in human complement factor I as determined by a combination of X-ray and neutron scattering and homology modeling.

Human factor I is a multidomain plasma serine protease with one factor I-membrane attack complex (FIMAC) domain, one CD5 domain, two low-density lipoprotein receptor (LDLr) domains, and one serine protease (SP) domain and is essential for the regulation of complement. The domain arrangement in factor I was determined by X-ray and neutron scattering on serum-derived human factor I (sFI) and recombinant insect cell factor I (rFI). While the radii of gyration of both were the same at 4.05 nm and both had overall lengths of 14 nm, the cross-sectional radii of gyration were different at 1.70 nm for sFI and 1.57 nm for rFI. This difference was attributed to their different means of glycosylation which is complex-type for sFI and high-mannose-type for rFI. Homology models were constructed for the FIMAC, LDLr, and SP domains of factor I using related crystal structures, and CD5 was represented as a globular protein by referencing its electron microscopy dimensions. In these models, 38 of the 40 Cys residues in factor I were predicted to form internal disulfide bridges. The two remaining Cys residues at the N terminus of the FIMAC domain and at the center of the first LDLr domain were potentially not bridged. It was postulated that, if these two Cys residues were bridged to each other, the FIMAC, CD5, and LDLr-1 domains would form a compact triangular arrangement. This hypothesis was tested by automated scattering curve fit searches based on 9600 bilobal models, setting the FIMAC, CD5, and LDLr-1 domains as one lobe and the large SP domain as the other lobe. The searches gave a single small family of similar structures with a separation of 5.9 nm between the centers of the lobes which gave similar good X-ray and neutron fits for both sFI and rFI, despite the different glycosylations of sFI and rFI. These best-fit structures for factor I showed that this domain model is plausible, and suggested that the SP and the CD5 and LDLr-1 domains may present exposed surfaces in factor I whose roles are to interact separately with its substrates C3b and C4b and with cofactor proteins.

Amino Acid Sequence↗