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Biomedical subjects

C Weston

Publications and source records attributed to C Weston.

At least 19 recordsLinked to original sources
PubMed2006

A phase I study of intravenous liposomal daunorubicin (DaunoXome) in paediatric patients with relapsed or resistant solid tumours.

Anthracyclines are widely used in paediatric oncology, but their use is limited by the risk of cumulative cardiac toxicity. Encapsulating anthracyclines in liposomes may reduce cardiac toxicity and possibly increase drug availability to tumours. A phase I study in paediatric patients was designed to establish the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) after a single course of liposomal daunorubicin, 'DaunoXome', as a 1 h infusion on day 1 of a 21 day cycle. Patients were stratified into two groups according to prior treatment: Group A (conventional) and group B (heavily pretreated patients). Dose limiting toxicity was expected to be haematological, and a two-step escalation was planned, with and without G-CSF support. Pharmacokinetic studies were carried out in parallel. In all, 48 patients aged from 1 to 18 years were treated. Dose limiting toxicity was neutropenia for both groups. Maximum tolerated dose was defined as 155 mg m(-2) for Group A and 100 mg m(-2) for Group B. The second phase with G-CSF was interrupted because of evidence of cumulative cardiac toxicity. Cardiac toxicity was reported in a total of 15 patients in this study. DaunoXome shares the early cardiotoxicity of conventional anthracyclines in paediatric oncology. This study has successfully defined a haematological MTD for DaunoXome, but the significance of this is limited given the concerns of delayed cardiac toxicity. The importance of longer-term follow-up in patients enrolled into phase I studies has been underestimated previously, and may lead to an under-recognition of important adverse events.

Adolescent↗
PubMed2005

Redefining the coronary care unit: an observational study of patients admitted to hospital in England and Wales in 2003.

BACKGROUND: Coronary care units were developed in the 1960s as specially equipped and staffed areas where patients with acute myocardial infarction could be monitored and offered rapid resuscitation from life-threatening arrhythmias. Awareness of the morbidity and mortality of the wider spectrum of acute coronary ischaemia was unrecognized at that time. AIM: To examine the relative frequencies with which thrombolytic treatment and resuscitation from cardiac arrest are provided for patients with myocardial infarction in cardiac care units (CCUs), emergency departments (EDs) and other medical wards. DESIGN: Observational study. METHODS: We analysed records from the National Audit of Myocardial Infarction Project (MINAP) for 61 688 patients admitted to 230 acute hospitals in England and Wales during 2003, and who received a final diagnosis of myocardial infarction, for locations of initiation of thrombolytic therapy and of first cardiac arrest within hospital. RESULTS: Overall, 84% of 27 881 patients with ST-segment-elevation infarction, but only 42% of 30 382 patients with non-ST-elevation infarction, were admitted to a CCU. Of those receiving thrombolytic treatment for ST-elevation infarction, 68.3% of 21 595 did so in the ED. Within the first 4 h after arrival, the majority of episodes of cardiac arrest occurred in the ED: 709 (57%) vs. 488 (39%) in CCU, and 49 (4%) in medical wards. DISCUSSION: The traditional role of the CCU in providing early resuscitation and thrombolytic treatment for patients with ST elevation infarction has largely been devolved to the ED. The role of the CCU should be re-evaluated, and the service re-designed to provide specialist care for all presentations of acute coronary syndrome.

Aged↗
PubMed2005

The heart and the oesophagus: intimate relations.

The close anatomical relations of the heart and oesophagus, and the similarity of symptoms attributable to disorders of either organ, often lead to diagnostic difficulty in patients with chest pain. A definitive diagnosis of non-cardiac chest pain attributable to oesophageal reflux or spasm is hampered, both by the need for prolonged ambulatory monitoring of pH, manometry, and endoscopy, and by the common occurrence of asymptomatic reflux and spasm, and the corresponding difficulty in linking an episode of reflux or spasm with an episode of pain. Moreover, some patients with non-cardiac chest pain and normal tests of oesophageal structure and function have centrally mediated hypersensitivity, both within and without the oesophagus. Rather than proceed with investigations, in the absence of symptoms to suggest structural disease of the oesophagus, it would be reasonable to attempt symptomatic treatment with a proton pump inhibitor or an antidepressant.

Antidepressive Agents, Tricyclic↗
PubMed2004

Improving care for patients with acute coronary syndromes: initial results from the National Audit of Myocardial Infarction Project (MINAP).

OBJECTIVE: To describe the improvements in care that have followed the introduction of an electronic data entry and analysis system providing contemporary feedback on the management of acute coronary syndromes in 230 hospitals in England and Wales. DESIGN: Observational study METHODS: A secure electronic system was used to transfer encrypted data on patients with acute coronary syndromes from collaborating hospitals to central servers for analysis. Immediate online data entry to the central servers by hospitals allowed contemporary analyses of performance and immediate comparison with the national aggregate performance. RESULTS: The records of 156 902 patients receiving a final diagnosis of acute coronary syndrome during three years between October 2000 and September 2003 were analysed. Of 69 113 patients with ST segment elevation infarction, 75.4% received thrombolytic treatment. Between the first and last years of the study the median interval from hospital arrival to treatment fell for eligible patients from 38 (interquartile range 22-58) to 20 (interquartile range 14-28) minutes. By mid 2003 77.6% were receiving thrombolytic treatment within 30 minutes of arrival. The proportion treated within two hours of onset of symptoms increased from 32.5% to 40.3% (a difference of 7.8 percentage points, p < 0.0001). The use of secondary prevention medication for acute coronary syndromes increased over this period: angiotensin converting enzyme inhibitors, 62.4% to 72.4%; beta blockers, 76.3% to 82.6%; statins, 69.6% to 83.8%; and aspirin, 89.3% to 90.2%. CONCLUSION: The provision of contemporary online performance analyses has underpinned substantial improvement in the care of patients with acute coronary syndromes.

Adrenergic beta-Antagonists↗
PubMed2004

Antiplatelet agents in atherothrombotic diseases.

Atherothrombotic disease places a huge financial and social burden on the nation, and antiplatelet therapy is important in preventing this. Aspirin is most widely used but newer compounds are valuable, especially on top of standard therapy in patients with unstable angina or non-ST segment elevation myocardial infarction. This article reviews the changing use of antiplatelets.

Arteriosclerosis↗
PubMed2003

Antiplatelet drugs in cardiovascular diseases.

Platelets play a key role in the pathogenesis of atherothrombotic conditions, e.g. acute coronary syndromes, cerebrovascular and peripheral vascular events. Antiplatelet agents interfere with platelet activation and aggregation and, as such, would be expected to modify the natural history of cardiovascular disease. In this review we explore the evidence to support the use of such drugs, singly or in combination, in a variety of situations characterised by thrombosis and summarise some of the concerns inherent in their use.

Aspirin↗
PubMed2002

Limited effect of recombinant porcine interleukin-12 on porcine lymphocytes due to a low level of IL-12 beta2 receptor.

The cytokine interleukin-12 (IL-12) is a key molecule in the regulation of CD4 + T cell development and specifically potentiates T helper 1 responses in mouse and man. However, biological effects mediated by IL-12 have not been well defined in pigs. Herein, recombinant porcine IL-12 (rPoIL-12) was expressed in a swine poxvirus system as a biologically active heterodimer and used to stimulate bovine or swine lymphoblast cells. After 3 days of incubation, only bovine blasts were responsive to the rPoIL-12 treatment as monitored by cell proliferation in several independent trials. Similarly, i.m. administration of rPoIL-12 in the hind leg of 3-week-old pigs indicated a reduction in the number of interferon-gamma (IFN-gamma) producing lymphocytes isolated from inguinal lymph nodes. The porcine IL-12R beta2 (IL-12Rbeta2) sequence was cloned and results generated by reverse transcriptase polymerase chain reaction (RT-PCR) demonstrated that the expression of IL-12R on porcine blasts as measured by the relative levels of IL-12Rbeta2 mRNA was less than that in bovine blasts and are in agreement with the reduced proliferation response of swine blast cells to rPoIL-12 treatment. Real time PCR analysis demonstrated that after PBMC stimulation, bovine blasts had an 11-fold increase in IL-12Rbeta2 mRNA levels while porcine blasts had almost no change. These data support a mechanism for IL-12 stimulation in swine inconsistent with that observed in conventional models.

Amino Acid Sequence↗
PubMed2002

Changing the diagnostic criteria for myocardial infarction in patients with a suspected heart attack affects the measurement of 30 day mortality but not long term survival.

OBJECTIVES: To explore the effects of alternative methods of defining myocardial infarction on the numbers and survival patterns of patients identified as having sustained a confirmed myocardial infarct. DESIGN: An inclusive historical cohort of patients admitted with a suspected heart attack. Patients were recoded from raw clinical data (collected at the index admission) to the epidemiological definitions of myocardial infarction used by the Nottingham heart attack register (NHAR), the World Health Organization (MONICA), and the UK heart attack study. SETTING: Single health district. PATIENTS: The NHAR identified all patients admitted in 1992 with suspected myocardial infarction. OUTCOME MEASURES: Survival at 30 days and four year postdischarge. RESULTS: 2739 patients were identified, of whom 90% survived to discharge. Recoding increased the numbers of patients defined as having confirmed myocardial infarction from 26% under the original NHAR classification to 69%, depending on the classification system used. In confirmed myocardial infarction, subsequent 30 day survival from admission varied from 77-86% depending on the classification system; four year survival after discharge was not affected. The distribution of important prognostic variables differed significantly between groups of patients with confirmed myocardial infarction defined by different systems. Patients with suspected but unconfirmed myocardial infarction under all classification systems had a worse postdischarge mortality. CONCLUSIONS: The classification system used had a substantial effect on the numbers of patients identified as having had a myocardial infarct, and on the 30 day survival. There were significant numbers of patients with more atypical presentations, not labelled as myocardial infarction, who did badly following discharge. More research is needed on these patients.

Age Factors↗
PubMed2000

Agrin-induced acetylcholine receptor clustering is mediated by the small guanosine triphosphatases Rac and Cdc42.

During neuromuscular junction formation, agrin secreted from motor neurons causes muscle cell surface acetylcholine receptors (AChRs) to cluster at synaptic sites by mechanisms that are insufficiently understood. The Rho family of small guanosine triphosphatases (GTPases), including Rac and Cdc42, can mediate focal reorganization of the cell periphery in response to extracellular signals. Here, we investigated the role of Rac and Cdc42 in coupling agrin signaling to AChR clustering. We found that agrin causes marked muscle-specific activation of Rac and Cdc42 in differentiated myotubes, as detected by biochemical measurements. Moreover, this activation is crucial for AChR clustering, since the expression of dominant interfering mutants of either Rac or Cdc42 in myotubes blocks agrin-induced AChR clustering. In contrast, constitutively active Rac and Cdc42 mutants cause AChR to aggregate in the absence of agrin. By indicating that agrin-dependent activation of Rac and Cdc42 constitutes a critical step in the signaling pathway leading to AChR clustering, these findings suggest a novel role for these Rho-GTPases: the coupling of neuronal signaling to a key step in neuromuscular synaptogenesis.

Agrin↗
PubMed1999

Cardiac rehabilitation: socially deprived patients are less likely to attend but patients ineligible for thrombolysis are less likely to be invited.

OBJECTIVE: To identify factors associated with the uptake of cardiac rehabilitation following acute myocardial infarction. DESIGN: Retrospective analysis using multivariate logistic regression modelling. SETTING: Two large teaching hospitals in Nottingham. PATIENTS: Cohorts of patients admitted with acute myocardial infarction in 1992 and 1996. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Factors in multivariate analysis found to be associated with attendance at cardiac rehabilitation. Use of secondary prevention in those who were and were not invited and those who did and did not attend cardiac rehabilitation. RESULTS: 58% of all patients were offered cardiac rehabilitation. Attendance rates were 60% in 1992 and 74% in 1996. Invitations were more likely to be offered to younger patients, those who had received thrombolysis, and to patients admitted to one of the two Nottingham hospitals. Use of secondary prevention was only 48% in 1992 but this increased to 80% in 1996. Patients not receiving secondary prevention were less likely to be invited to cardiac rehabilitation. Social deprivation was the only factor significantly associated with poor uptake of cardiac rehabilitation in both years. There was no difference in the use of secondary prevention between those who did and did not attend cardiac rehabilitation. CONCLUSION: Those invited to attend a cardiac rehabilitation programme are likely to be in a good prognosis group, comprising those who are young and have received thrombolysis. Those at greatest risk, particularly patients from socially deprived areas, seem to be missing out on the potential benefits of cardiac rehabilitation. High risk patients should be specifically targeted to ensure that they are invited to, and encouraged to, attend a programme of cardiac rehabilitation.

Adult↗
PubMed1997

Immunological response in the primate oviduct to a defined recombinant sperm immunogen.

Assessment of immune responses in the oviduct is of importance in understanding reproductive tract responses to infections, vaccination against reproductive tract pathogens, or contraceptive immunogens. This review discusses a technique that permits repeated sampling of oviductal fluid from the same monkey at intervals spanning up to several years, and the analysis of antigen-specific immunoglobulins in the fluid. This technique is important to immunocontraceptive development because previous studies in primates have lacked information on oviductal immune responses and contraceptive efficacy may not correlate well with serum antibody titers. Thus, a reliable method of sampling oviductal fluid before and after immunization with a defined antigen is required to determine the quantity and type of local immune responses necessary to achieve contraceptive effects. Implantation of access ports proved useful for repeatedly aspirating oviductal fluid in vivo from cynomolgus monkeys that was free from artifactual contaminants and with no observable changes in the behavior or health of the animals. Subsequent assays of relative and absolute concentrations of antibodies in oviductal fluid and serum demonstrated the presence of IgA and IgG specific for the recombinant sperm immunogen SP-10 in fluid collected from the periovulatory oviduct of primates after intramuscular inoculations. The antibodies evoked by the recombinant sperm vaccinogen recognized the endogenous antigen target on both human and macaque sperm, lending support for the possibility of developing a contraceptive immunogen that prevents fertilization.

Acrosome↗
PubMed1997

Waiting times. Bones of contention.

A slot system allocating a set number of outpatient orthopaedic appointments to general practices in North West Anglia HA means all patients referred are seen in eight weeks. The system has provoked criticism from GPs on the grounds that the burden of waiting lists has shifted onto them, and it limits access to services. The scheme has improved communication between GPs and orthopaedic consultants.

Appointments and Schedules↗
PubMed1997

Is peer tutoring beneficial in the context of school resuscitation training?

First year pupils at a Cardiff comprehensive school were trained in cardiopulmonary resuscitation, 106 by the teacher only and 137 by the teacher assisted by older pupils (peer tutoring). Scores in a multiple choice theory test and in practical skill assessment showed no significant difference between instruction methods, but boys taught by the teacher assisted by older pupils expressed less willingness to resuscitate in an emergency than girls instructed by either method (P < 0.01). Girls had higher scores in the multiple choice paper (P < 0.025) and in the skills assessment (P < 0.01). Those pupils who reported some prior knowledge of resuscitation techniques performed better during skill assessment than novice trainees (P < 0.025).

Adolescent↗
PubMed1997

Oviductal antibody response to a defined recombinant sperm antigen in macques.

Macaque oviductal fluids were assayed for specific antibodies to the intra-acrosomal sperm protein SP-10 after immunizations with recombinant macaque SP-10 (re-mqSP-10), a candidate contraceptive vaccinogen. Access ports, consisting of a subcutaneous collecting reservoir and a catheter to cannulate the oviduct, were implanted into monkeys for repeated aspiration of oviductal fluid. Monkeys were inoculated i.m. once a month with an emulsion consisting of 2 mg re-mqSP-10 in a vehicle of squalene and mannin monooleate. Oviductal fluids and serum were collected during the periovulatory period for six menstrual cycles, and IgG and IgA antigen-specific antibodies in preimmune and immune fluids were compared by ELISA. Both relative and absolute concentrations of SP-10-specific immunoglobulins (Ig) were determined. Oviductal fluids from immunized animals showed significant increases in anti-SP-10 IgG at cycle 2 and at all subsequent intervals. Anti-SP-10 IgA significantly increased in oviductal fluid at cycles 4, 5, and 6. Serum anti-SP-10 IgG increased at cycle 2 and remained significantly elevated through cycle 6, while serum anti-SP-10 IgA was higher than in preimmune samples at cycle 4. Serum antibodies generated to the recombinant SP-10 recognized SP-10 extracted from macaque sperm on Western blots. Immunocytochemical staining of macaque and human sperm showed acrosomal immunofluorescence with both immune oviductal fluids and serum using both anti-IgG and anti-IgA secondary antibodies. This study demonstrates for the first time 1) IgG and IgA antibodies to a defined recombinant sperm-specific antigen in primate oviductal fluids after systemic immunization and 2) the recognition by primate oviductal fluid IgG and IgA of the endogenous contraceptive target on both human and macaque sperm.

Acrosome↗
PubMed1996

Teaching schoolchildren cardiopulmonary resuscitation.

Forty-one children aged 11-12 years received tuition in cardiopulmonary resuscitation (CPR) and subsequently completed questionnaires to assess their theoretical knowledge and attitudes their likelihood of performing CPR. Although most children scored well on theoretical knowledge, this did not correlate with an assessment of practical ability using training manikins. In particular only one child correctly called for help after the casualty was found to be unresponsive, and none telephoned for an ambulance before starting resuscitation. These omissions have important implications for the teaching of CPR and the resulting effectiveness of community CPR programmes.

Ambulances↗