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D Chamberlain

Publications and source records attributed to D Chamberlain.

At least 19 recordsLinked to original sources
PubMed2006

Intrinsic stability and functional properties of disulfide bond-stabilized coagulation factor VIIIa variants.

BACKGROUND: The utility of purified coagulation factor (F)VIII for treatment of hemophilia A is limited in part by its instability following activation by thrombin, which is caused by spontaneous dissociation of the A2 domain from the activated FVIII (FVIIIa) heterotrimer. To prevent this A2 domain dissociation in FVIIIa, we previously engineered a cysteine pair (C664-C1826) in recombinant FVIII that formed a disulfide bond cross-linking the A2 domain in the heavy chain to the A3 domain in the light chain. This engineered disulfide bond resulted in a more stable FVIIIa. AIMS: Here, we characterize the functional parameters of C664-C1828 FVIII and of a new disulfide bond-stabilized FVIII (C662-C1828 FVIII). METHODS: In order to assess whether these FVIII variants might be good candidates for a new therapeutic agent to treat hemophilia A, we investigated a variety of functional parameters that might affect the in vivo properties of the variants, including half-life of disulfide bond-stabilized FVIII and FVIIIa and the potency of these FVIIIa molecules in the FXase complex. RESULTS: Both disulfide bond-stabilized variants had improved affinity for von Willebrand factor (VWF). In studies of FX activation by purified FIXa and FVIIIa, C662-C1828 FVIIIa had normal activity while C664-C1826 FVIIIa had reduced activity. Both C664-C1826 FVIIIa and C662-C1828 FVIIIa were inactivated by activated protein C (APC) but the rates of inactivation were different. CONCLUSION: Overall, the specific location of the disulfide bridge between the A2 and A3 domains appears to affect functional properties of FVIIIa. In summary, introduction of engineered interdomain disulfides results in FVIIIa variants that resist spontaneous loss of activity while retaining susceptibility to APC proteolytic inactivation and maintaining VWF binding.

Factor IXa↗
PubMed2005

International multicentre trial protocol to assess the efficacy and safety of tenecteplase during cardiopulmonary resuscitation in patients with out-of-hospital cardiac arrest: the Thrombolysis in Cardiac Arrest (TROICA) Study.

Prehospital cardiac arrest has been associated with a very poor prognosis. Acute myocardial infarction and massive pulmonary embolism are the underlying causes of out-of-hospital cardiac arrest in 50-70% of patients. Although fibrinolysis is an effective treatment strategy for both myocardial infarction and pulmonary embolism, clinical experience for this therapy performed during resuscitation has been limited owing to the anticipated risk of severe bleeding complications. The TROICA study is planned as one of the largest randomized, double-blind, placebo-controlled trials to assess the efficacy and safety of prehospital thrombolytic therapy in cardiac arrest of presumed cardiac origin. Approximately 1000 patients with cardiac arrest will be randomized at approximately 60 international study centres to receive either a weight-adjusted dose of tenecteplase or placebo after the first dose of a vasopressor. Patients can be included if they are at least 18 years, presenting with a witnessed cardiac arrest of presumed cardiac origin, and if either basic life support had started within 10 min of onset and had been performed up to 10 min or advanced life support is started within 10 min of onset of cardiac arrest. Primary endpoint of the study is the 30-day survival rate, and the coprimary endpoint is hospital admission. Secondary endpoints are the return of spontaneous circulation (ROSC), survival after 24 h, survival to hospital discharge, and neurological performance. Safety endpoints include major bleeding complications and symptomatic intracranial haemorrhage.

Adolescent↗
PubMed2005

Primary pleural epithelioid haemangioendothelioma with metastases to the skin. A case report and literature review.

Epithelioid haemangioendothelioma (EHE) is a rare vascular tumour of intermediate behaviour. It can arise from various sites including the liver, spleen, pleura, or lung. Cutaneous EHE can be primary or secondary. This report describes the case of a 51 year old man who presented with a history of dry cough, shortness of breath, and pleural effusion, and who developed two cutaneous nodules in the anterior abdominal wall a few weeks later. He had a previous history of asbestos exposure. Computed tomography scan showed a left sided pleural effusion and nodular pleural mass. Histology of both the pleural and cutaneous lesions was compatible with EHE. Electron microscopic examination demonstrated the presence of Weibel-Palade bodies. The patient underwent elliptical excision of the metastatic cutaneous nodules after decortication of the primary pleural tumour and adjuvant treatment. A few reports have described metastasis of intrathoracic EHE to the skin. Despite treatment with interferon, the patient developed more cutaneous lesions two years after the initial diagnosis. Even though the tumour has the classic light histological and ultrastructural features of EHE, it behaved in an aggressive manner.

Biomarkers, Tumor↗
PubMed2002

Coronary angioplasty versus medical therapy for angina. Health service costs based on the second Randomized Intervention Treatment of Angina (RITA-2) trial.

AIMS: The second Randomized Intervention Treatment of Angina (RITA-2) trial compares an initial strategy of PTCA with continued medical management in patients with arteriographically proven coronary artery disease. This paper employs resource use data collected in the trial to compare the health service costs of the two strategies over 3 years follow-up. METHODS AND RESULTS: 1018 patients were randomized, 504 to PTCA and 514 to continued medical management. Health service resource use data were collected prospectively on all patients. Hospital unit costs were estimated in collaboration with five U.K. centres. PTCA patients underwent more subsequent coronary arteriograms, but subsequent (non-randomized) PTCAs were more common in patients randomized to medical management (118 procedures in 102 patients) compared to those randomized to PTCA (73 procedures in 62 patients). The likelihood of undergoing CABG was similar in the two groups. The use of antianginal medications was higher in patients randomized to an initial strategy of medical management. There was an overall mean additional cost per patient over 3 years in patients randomized to PTCA of pound 2685 (95% CI pound 2074- pound 3322). CONCLUSIONS: In RITA-2, the cost of an initial strategy of PTCA exceeded the cost of an initial strategy of medical management by 74% over 3 years.

Angina Pectoris↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

Anaphylaxis management in primary care.

The United Kingdom Resuscitation Council Project Team has issued revised guidelines on the emergency treatment of anaphylactic reactions in the community setting in response to community nurses' concerns. A consensus has now been reached.

Anaphylaxis↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed1999

Pre-hospital thrombolysis.

The administration of thrombolytic drugs outside hospital by emergency physicians is becoming more common. However, few in Europe live in areas where such a service is provided. The data suggest that the advantages can be appreciable in some circumstances but that the strategy may not be universally applicable.

Journal Article↗