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Biomedical subjects

C Rooney

Publications and source records attributed to C Rooney.

At least 19 recordsLinked to original sources
PubMed2006

Changes to the daily pattern of methadone-related deaths in England and Wales, 1993-2003.

Previous studies suggest that fatal poisoning deaths involving methadone occur more frequently on the weekends. We assessed changes in the daily pattern of mortality because of methadone poisoning following a review of drug misuse services in 1996 and publication of revised clinical guidelines in 1999. We also compared this to the daily pattern of deaths involving heroin/morphine. The Office for National Statistics provided data on all deaths in England and Wales between 1993 and 2003 for which methadone and heroin/morphine were mentioned on the coroner's certificate of death registration after inquest, with or without alcohol or other drugs. There were 3098 deaths involving methadone. The death rate increased up to 1997 and then declined. Initially, there was a marked excess of deaths occurring on Saturdays. The rate of decline was greatest for deaths occurring on Saturdays. As a result, the Saturday peak disappeared (P = 0.006). There were 6328 deaths involving heroin/morphine. No change in the daily pattern of heroin/morphine deaths was observed during the study period. Although the marked change in the epidemiology of methadone deaths coincided with recommendations for service redevelopment and clinical management of methadone treatment, the contribution of improved prescribing practice or treatment services is unclear.

Death Certificates↗
PubMed2005

Fatal poisoning in childhood, England & Wales 1968-2000.

We analysed deaths certified as due to poisoning in England & Wales, 1968-2000, in children aged <10 years by age, sex, circumstances of death, intent, and agents involved. The number of deaths fell from 165 (20.6 per million children) in 1968 to 30 (4.6 per million) in 2000, a decrease of approximately 80%. The age-specific death rates were similar in boys and girls. The rate was initially much higher, and fell more, in those aged <5 years. Most deaths (n=1923) occurred in fires, and had been attributed to inhaling combustion products. A small number (n=104) occurred in fires resulting from motor vehicle and other transport accidents. From 1979 (use of ICD-9) the coding of some of these deaths changed from poisoning with carbon monoxide to poisoning with 'other gases, fumes or vapours'. These 'fire deaths' do not appear as poisonings in mortality statistics based on a single underlying cause of death, and cannot be tabulated as poisoning in many countries. Fire deaths and deaths coded to accidental, deliberate, or undetermined poisoning (n=702) decreased substantially with time, and by 2000 numbered 14 and 10, respectively. Accidental deaths declined from 151 in 1968 to 23 in 2000, but homicides and open verdicts varied from 5 to 20 per year, with no clear trend. Deaths attributed to carbon monoxide and to 'other gases, fumes or vapours' (mostly fire-related) totalled 2431 (84% of all poisoning deaths). Overall, 10% of these deaths were either certified as homicides or open verdicts. However, homicide or open verdict was recorded in half of the 47 fatal opiate poisonings. Opioids have now superseded antidepressants as the commonest agents encountered in fatal poisoning with drugs in children.

Accidents↗
PubMed2005

Population based mortality and quality of death certification in progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome).

OBJECTIVE: To estimate the mortality of progressive supranuclear palsy (PSP) and to assess the quality of death certification in patients with PSP who died in England and Wales. METHODS: An analysis was conducted of ICD-9 (International Classification of Diseases, version 9) coded deaths obtained through the Office of National Statistics over an eight year period. RESULTS: The crude annual mortality rate was 1.77 (95% confidence interval, 1.64 to 1.90) cases per million, using the mid-1996 population estimate for England and Wales. Annual mortality increased over time, possibly as a result of increased incidence or increased awareness of the disorder. Forty nine death certificates from deceased patients previously diagnosed clinically showed that the commonest proximate cause of death was pneumonia, occurring in 45% of cases (22/49). The underlying cause of death was cited as pneumonia in 14% of cases (7/49). PSP was mentioned in only 65% of death certificates (32/49). Eight of the 49 cases (16%) underwent necropsy and results were available for five of these cases. PSP was confirmed pathologically in four; the remaining case was diagnosed as Parkinson's disease. CONCLUSIONS: Further research is needed to establish the reasons for the observed increase in mortality. Determining the population mortality rate for PSP using the ICD-9 coding system is problematic but is likely to improve following the introduction of ICD-10 updated codes and coding rules.

Autopsy↗
PubMed2002

Recording acute poisoning deaths.

Recording deaths from acute poisoning/substance abuse is not straightforward. The International Classification of Diseases (ICD), used to code mortality statistics, is aimed towards recording the underlying cause of death such as suicide or drug dependence rather than gathering data on poisoning per se. Despite the inherent difficulties clear trends can be observed from the data available for England and Wales. There have been marked changes in the compounds featuring in suicidal poisoning in the last 35 years reflecting changes in the availability of poisons, notably carbon monoxide and prescription barbiturates. However, although the number of poisoning suicides has decreased in the recent years, suicides from other means have increased in males (suicides in 1999, 75% male), hence there has been little change in the annual total of suicides. There are also striking differences in drug abuse- and volatile substance abuse (VSA)-related deaths between males and females. Drug abuse-related fatal poisoning (83% male, 1979-1999, European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) definition which does not include suicide), largely attributable to heroin and methadone, increased markedly during the 1990s, with a sharp rise in deaths attributed to accidental poisoning, although deaths involving methadone are now declining. VSA-related deaths (90% male, 1971-1999, almost entirely accidental deaths), nowadays predominantly from abuse of fuel gases (liquefied petroleum gas, LPG) from, for example, cigarette lighter refills, have declined from a peak in the early 1990s and are now becoming manifest in an older age group. These two latter instances especially provide examples where ICD-derived fatal poisoning data are inadequate and a 'poisons oriented' approach to data collection and analysis is necessary.

Adolescent↗
PubMed2002

Deaths from pertussis are underestimated in England.

AIMS: To improve estimates of deaths from pertussis in England and to identify reasons for under ascertainment. METHODS: Comparison of deaths identified from enhanced laboratory pertussis surveillance, hospital episode statistics (HES), and Office for National Statistics (ONS) death registrations in England, 1994 to 1999. RESULTS: A total of 33 deaths were identified, 88% of infants less than 4 months old. There was overlap between all sources; 22 deaths were identified in the enhanced pertussis surveillance system, 18 in ONS mortality data, and nine in HES. Children who had died from pertussis without mention of pertussis on the death certificate were more likely to have been certified by coroners than those with mention of pertussis (p = 0.0005). Using capture-recapture analysis, the total number of deaths from pertussis in the five and a half year period is estimated to be 46 (95% CI 37 to 71), or around nine deaths per year. CONCLUSIONS: National mortality statistics significantly under estimate deaths from pertussis in England and are inadequate for monitoring the national immunisation programme. The largest number of deaths is identified through enhanced laboratory surveillance. Death registration systems should take into account available microbiological information to ensure that cause of death is accurately assigned.

Cause of Death↗
PubMed2001

Correction of DiGeorge anomaly with EBV-induced lymphoma by transplantation of organ-cultured thymus and Epstein-Barr-specific cytotoxic T lymphocytes.

A young woman with DiGeorge anomaly showed normal immune tests as a child and did not experience the symptoms of profound T cell immunodeficiency. However, she had chronic pulmonary infections which led to bronchiectasis. At age 14, she developed an Epstein-Barr virus-induced lymphoma and her T cell function tests were markedly abnormal. After intensive chemotherapy, she received an organ-cultured thymus transplant but because of an abnormally high EBV DNA titer was also given autologous EBV-specific cytotoxic T cells, prepared prior to transplant. Titers fell from 80,000 genome copies/mg DNA to 2000 within 6 weeks. She was clinically well and her T cell tests improved. Sixteen months after the transplant, however, her tumor returned; EBV DNA levels had risen to 40,000 copies/mg DNA. She again received autologous EBV-specific cytotoxic T lymphocytes and valcyclovir and Cytogam as well. Her tumor resolved on this therapy and she has remained well to this date, 29 months after the recurrence. T cell tests, which had deteriorated with the recurrence of the tumor, now show normal responses. This experience records a number of unique features of thymus transplantation. This is the first recorded successful thymus transplant in a patient with partial T cell immunity and thus expands the potential of this treatment modality to patients other than infants with complete DiGeorge anomaly. The patient demonstrates cytotoxic activity against mouse cells, demonstrating the ability to respond to a new antigen which requires host antigen presenting cells. Measurement of alpha 1 TRECs (T cell receptor excision circles) shows evidence of increasing and sustained thymopoiesis since the transplant at a level consistent with the age of the transplant donor rather than that of the recipient.

Biopsy↗
PubMed2001

Adenovector-induced expression of human-CD40-ligand (hCD40L) by multiple myeloma cells. A model for immunotherapy.

OBJECTIVE: CD40L restores the antigen-presenting cell (APC) function of some B-cell tumors and induces professional APC maturation. We therefore evaluated the effects of transgenic CD40L expression on the behavior and immunogenicity of human multiple myeloma (MM) cells. MATERIALS AND METHODS: CD40L expression was induced in a CD40(+) (RPMI 8226) and a CD40(-) (U266B1) human myeloma cell line (HMCL) by adenoviral vector gene transfer. The viability and proliferative activity of control HMCL and HMCL/CD40L were determined by daily trypan blue staining and methyl-3H-thymidine incorporation. Mixed lymphocyte reaction (MLR) with allogeneic mononuclear cells (MNCs) and coculture of allogeneic dendritic cells (DCs) with HMCL expressing transgenic CD40L were used to evaluate the APC function of modified HMCL as well as the role of bystander DCs in inducing an anti-tumor immune response. RESULTS: CD40L expression significantly inhibited the growth of the CD40(+) HMCL and induced apoptosis. These effects were less evident for the CD40(-) HMCL. There was no upregulation of costimulatory molecules on either HMCL following CD40L expression. Both HMCL expressing transgenic CD40L induced maturation of bystander DCs and enhanced their ability to stimulate the proliferation of MNCs. DCs cultured with the poorly immunogenic RPMI 8226 expressing CD40L upregulated T-lymphocyte release of IFN-gamma and other Th1 cytokines (interleukin-2, tumor necrosis factor-alpha). CONCLUSIONS: Our data suggest that transgenic expression of CD40L exerts a dual effect favoring generation of an immune response to human MM. Where the tumor cells are CD40(+), the engagement of CD40 antigen by CD40L on tumor cells induces their apoptosis, allowing uptake of tumor-associated antigen by professional APC. Independently of tumor-cell expression of CD40, transgenic expression of CD40L on tumor cells allows them to stimulate CD40(+) APC, to increase their maturation and their capacity to stimulate cytotoxic T lymphocytes (CTL) that recognize the tumor-derived antigens the APC may have engulfed.

Adenoviridae↗
PubMed2001

How effective is antenatal care in preventing maternal mortality and serious morbidity? An overview of the evidence.

This is an overview of evidence of the effectiveness of antenatal care in relation to maternal mortality and serious morbidity, focused in particular on developing countries. It concentrates on the major causes of maternal mortality, and traces their antecedent morbidities and risk factors in pregnancy. It also includes interventions aimed at preventing, detecting or treating any stage along this pathway during pregnancy. This is an updated and expanded version of a review first published by the World Health Organization (WHO) in 1992. The scientific evidence from randomised controlled trials and other types of intervention or observational study on the effectiveness of these interventions is reviewed critically. The sources and quality of available data, and possible biases in their collection or interpretation are considered. As in other areas of maternal health, good-quality evidence is scarce and, just as in many aspects of health care generally, there are interventions in current practice that have not been subjected to rigorous evaluation. A table of antenatal interventions of proven effectiveness in conditions that can lead to maternal mortality or serious morbidity is presented. Interventions for which there is some promising evidence, short of proof, of effectiveness are explored, and the outstanding questions formulated. These are presented in a series of tables with suggestions about the types of study needed to answer them.

Evidence-Based Medicine↗
PubMed2000

Induction of vigorous helper and cytotoxic T cell as well as B cell responses by dendritic cells expressing a modified antigen targeting receptor-mediated internalization pathway.

Efficient Ag presentation is essential to induce effective cellular and humoral immune responses. Thus, one central goal of current immunotherapy and vaccine development is to enhance Ag presentation to induce potent and broad immune responses. Here, a novel Ag presentation strategy is developed by transducing dendritic cells (DCs) to produce an Ag for presentation as an exogenous Ag to efficiently induce both humoral and cellular immunity. The principle of this strategy is illustrated by genetically modifying DCs to secrete a model hepatitis B virus Ag fused with a cell-binding domain and to process the fusion Ag as an exogenous Ag after receptor-mediated internalization for MHC class I and II presentation. Vigorous Ag-specific CD4(+) helper and CD8(+) cytotoxic T cell, as well as B cell, responses were induced by the transduced DCs in mouse models. Thus, this novel strategy uses a receptor-mediated internalization process to efficiently induce all arms of the adaptive immunity and may provide a powerful means to develop potent vaccines and immunotherapies.

Animals↗
PubMed1999

Hypothalamo-pituitary-adrenal axis responses to lipopolysaccharide in male and female rats with adjuvant-induced arthritis.

We have previously demonstrated that rats with adjuvant-induced arthritis (AA) are unable to mount a hypothalamo-pituitary-adrenal (HPA) axis response to either psychological or physical stress. In the present study we have taken male and female rats with AA and injected these with lipopolysaccharide (LPS) as an acute immune challenge and assessed the effects of this challenge at all levels of the HPA axis. We have demonstrated that, in contrast to acute stress, there is an activation of the HPA axis in male AA rats in response to acute immune challenge which occurs at all levels of the HPA axis. The hypothalamic and pituitary response to LPS is intact in the female AA rat. However, there appears to be an impaired adrenal responsiveness in the AA female given LPS. The non-AA female is able to respond to LPS suggesting that this defect is not inherent but is a reaction to the development of inflammation. This hyporesponsiveness has major implications for the ability of the organism to survive infections or immune challenges which are potentially life threatening in the absence of release of anti-inflammatory glucocorticoids from the adrenal cortex. The implications of these changes in the female on the subsequent development of the disease and the mechanisms mediating these effects may provide a better understanding of the gender differences underlying susceptibility to autoimmune diseases.

Adrenocorticotropic Hormone↗
PubMed1998

Extensive cross-reactivity of adenovirus-specific cytotoxic T cells.

Although adenovirus is a major source of morbidity for immunocompromised individuals and a popular vector for gene therapy, little is known about the cellular immune responses it evokes in humans. Initial trials using adenovirus vectors have been disappointing, probably owing both to a preexisting immune response to Ad2 and Ad5, the most commonly used vector backbones, and to a response to the transgene. The former problem might be overcome by switching from the common type C adenoviruses, of which Ad2 and Ad5 are members, to other less common serotypes. Evidence for the feasibility of this approach has been provided by a rat model system. However, its success in humans depends on there being no immunological cross-reactivity between groups at the humoral or cellular level. Here, we examine the cross-reactivity of the cellular immune response to adenovirus in a human system, and find that human cytotoxic T lymphocytes (CTLs) prepared in vitro against an adenovirus from two of the six subgroups can lyse cells infected with adenoviruses from the other subgroups. Hence, the proposed use of adenovirus vectors from uncommon subgroups to evade memory immune response to subgroup C adenoviruses may not be successful. However, this same cross-reactivity indicates that adoptive transfer of CTLs generated in vitro against one adenovirus serotype may protect immunocompromised patients from infections by adenoviruses of all serotypes.

Adenoviridae↗
PubMed1998

Cytotoxic T cells and immunotherapy.

Promising immunotherapies for viral infections and malignancies reflect the successful, rapid translation of laboratory findings into clinical practice. Fletcher et al. [1] present imaging studies of Epstein-Barr virus (EBV)-associated lymphomas before and after immunotherapy. Here, we briefly review the scientific bases of such novel therapies, which have evolved from advances in understanding of immune effector cells, of the cytokines that drive immune responses, and of the mechanisms underlying cell death.

B-Lymphocytes↗
PubMed1998

Excess mortality in England and Wales, and in Greater London, during the 1995 heatwave.

STUDY OBJECTIVE: To assess the impact on mortality of the heatwave in England and Wales during July and August 1995 and to describe any difference in mortality impact between the Greater London urban population and the national population. DESIGN: Analysis of variation in daily mortality in England and Wales and in Greater London during a five day heatwave in July and August 1995, by age, sex, and cause. SETTING: England and Wales, and Greater London. MAIN RESULTS: An estimated 619 extra deaths (8.9% increase, approximate 95% confidence interval 6.4, 11.3%) were observed during this heatwave in England and Wales, relative to the expected number of deaths based on the 31-day moving average for that period. Excess deaths were apparent in all age groups, most noticeably in women and for deaths from respiratory and cerebrovascular disease. Using published daily mortality risk coefficients for air pollutants in London, it was estimated that up to 62% of the excess mortality in England and Wales during the heatwave may be attributable to concurrent increases in air pollution. In Greater London itself, where daytime temperatures were higher (and with lesser falls at night), mortality increased by 16.1% during the heatwave. Using the same risk coefficients to estimate the excess mortality apparently attributable to air pollution, more than 60% of the total excess in London was apparently attributable to the effects of heat. CONCLUSION: Analysis of this episode shows that exceptionally high temperatures in England and Wales, though rare, do cause increases in daily mortality.

Adolescent↗
PubMed1998

Prognostic scores for use in African meningococcal epidemics.

Current WHO guidelines for the case management of meningococcal infections during epidemics in developing countries often cannot be applied, largely because of the limited health resources in such countries. Several scoring scales based on clinical and laboratory features in numerous combinations have been developed for the management of meningococcal infections in developed countries, and these have facilitated early identification of patients with fulminant disease and thus early intervention and reduction in mortality. Unfortunately such scoring scales are not appropriate for use in developing countries. We identified hypotension, tachycardia, tachypnoea, delay in capillary refill time, coma, absence of neck stiffness and petechiae and/or purpura as simple prognostic factors of meningococcal disease. Two scores were developed: score I, which includes all seven prognostic factors, had a sensitivity and specificity of 80% and 94%, respectively. Score II, which excluded hypotension, had a sensitivity and specificity of 73.3% and 89.7%, respectively. Quick and simple scoring scales are therefore not only applicable but useful for the case management of patients in meningococcal epidemics in developing countries.

Adolescent↗
PubMed1998

Drug-related mortality: methods and trends.

Drug-related deaths attract widespread concern and public interest and this is reflected in the number of queries ONS receives on this topic. This article sets out the processes involved in the collection and compilation of data on drug-related deaths in England and Wales to serve as a point of reference for users of ONS mortality data. It also documents recent trends in drug-related deaths, revealing considerable variation in mortality by age, sex and region.

Adolescent↗