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E D Carrol

Publications and source records attributed to E D Carrol.

At least 19 recordsLinked to original sources
PubMed2006

Clinical and diagnostic findings of an echovirus meningitis outbreak in the north west of England.

INTRODUCTION: An outbreak of echovirus meningitis occurred in the north west of England in 2001. This paper reviewed the clinical features and the role of different diagnostic methods. METHODS: This was a prospective study of adults admitted to a regional infectious disease unit with a probable diagnosis of meningitis, March to August 2001. RESULTS: Half the 40 cases were male; median age was 28 (range 16-51) years. Fifteen of 38 (39.5%) were smokers, and 20 of 24 (83.3%) had close contact with children. Median (range) duration of symptoms was 1.1 (0.25-7) days. Symptoms included headache (100%), photophobia (87.5%), and nausea (67.5%), and severity ranged from minimal signs to those consistent with a meningoencephalitis. The diagnosis was confirmed virologically in 29 of 40 (72%); echovirus 30 was isolated from six. Cerebrospinal fluid (CSF) enterovirus polymerase chain reaction (PCR) was positive in 26 of 32 (81%), and CSF virus culture in 3 of 16 (19%). Thirty one per cent of CSF samples had a neutrophil predominance, and 3 of 29 (10%) virologically confirmed cases had normal CSF microscopy and biochemistry. CONCLUSION: CSF microscopy may be normal or suggest bacterial meningitis in a substantial minority of cases of echovirus meningitis. CSF PCR for enterovirus seems to be more sensitive than virus culture of CSF, although PCR does not yield information on circulating virus type. Early and accurate diagnosis could reduce both use of parenteral antibiotics and length of hospital stay with both morbidity and cost implications. Close contact with children may be a risk factor, particularly if good hygiene measures are not practised.

Adolescent↗
PubMed2003

Anhidrotic ectodermal dysplasia and immunodeficiency: the role of NEMO.

Anhidrotic (hypohidrotic) ectodermal dysplasia associated with immunodeficiency (EDA-ID; OMIM 300291) is a newly recognised primary immunodeficiency caused by mutations in NEMO, the gene encoding nuclear factor kappaB (NF-kappaB) essential modulator, NEMO, or inhibitor of kappaB kinase (IKK-gamma). This protein is essential for activation of the transcription factor NF-kappaB, which plays an important role in human development, skin homoeostasis, and immunity.

Child, Preschool↗
PubMed2002

Procalcitonin as a marker of sepsis.

Prompt diagnosis and treatment with appropriate antimicrobial chemotherapy is of paramount importance to reduce morbidity and mortality associated with sepsis. Inflammatory markers currently in use, such as C-reactive protein (CRP) do not reliably differentiate between the systemic inflammatory response and sepsis. Procalcitonin (PCT), a precursor of calcitonin, is a 116 amino acid protein that has been proposed as a marker of disease severity in conditions such as septicaemia, meningitis, pneumonia, urinary tract infection (UTI) and fungal and parasitic infection. In particular, serial measurements are useful in order to monitor response to therapy. Together with good clinical judgement and judicious use of antimicrobial agents, PCT should serve as a valuable adjunct in the diagnosis and management of sepsis.

Biomarkers↗
PubMed2002

Myositis in children with meningococcal disease: a role for tumour necrosis factor-alpha and interleukin-8?

OBJECTIVES: Myalgia is under-recognized in meningococcal disease (MCD). In septic shock, myositis is thought to be mediated by pro-inflammatory cytokines such as tumour necrosis factor-alpha (TNF-alpha), interleukin-8 (IL-8) and interleukin-6 (IL-6) but this has never previously been studied in MCD. We aimed to demonstrate whether muscle damage mediated via TNF-alpha and other pro-inflammatory cytokines occurs in MCD, as estimated by creatine kinase skeletal muscle isoenzyme (CK-MM) and cardiac isoenzyme (CK-MB) concentrations. METHODS: A total of 68 children, median age 2.7 years, with a diagnosis of MCD were prospectively studied. Severity of disease was measured using the Glasgow Meningococcal Septicaemia Prognostic Score (GMSPS). Severe disease was defined as a GMSPS of > or =8. TNF-alpha, IL-8, IL-6 and IL-1Ra concentrations were determined on samples taken on admission. RESULTS: CK-MM correlated significantly with TNF-alpha, IL-8 and GMSPS. There was no significant correlation between CK-MB and TNF-alpha or IL-6, but CK-MB correlated with GMSPS and IL-8. Fifty-six percent of children with MCD had evidence of muscle damage as manifested by elevated CK-MM. CONCLUSIONS: TNF-alpha and IL-8 may be potential mediators in the pathophysiology of skeletal muscle damage in MCD.

Adolescent↗
PubMed2002

Procalcitonin as a diagnostic marker of meningococcal disease in children presenting with fever and a rash.

BACKGROUND: Procalcitonin (PCT), a precursor of calcitonin, is a recognised marker of bacterial sepsis, and high concentrations correlate with the severity of sepsis. PCT has been proposed as an earlier and better diagnostic marker than C reactive protein (CRP) and white cell count (WCC). This comparison has never been reported in the differentiation of meningococcal disease (MCD) in children presenting with a fever and rash. AIM: To determine if PCT might be a useful marker of MCD in children presenting with fever and rash. METHODS: PCT, CRP, and WCC were measured on admission in 108 children. Patients were classified into two groups: group I, children with a microbiologically confirmed clinical diagnosis of MCD (n = 64); group II, children with a self limiting illness (n = 44). Median ages were 3.57 (0.07-15.9) versus 1.75 (0.19-14.22) years respectively. Severity of disease in patients with MCD was assessed using the Glasgow Meningococcal Septicaemia Prognostic Score (GMSPS). RESULTS: PCT and CRP values were significantly higher in group I than in group II (median 38.85 v 0.27 ng/ml and 68.35 v 9.25 mg/l; p < 0.0005), but there was no difference in WCC between groups. Sensitivity, specificity, and positive and negative predictive values were higher for PCT than CRP and WCC. In group I, procalcitonin was significantly higher in those with severe disease (GMSPS >/=8). CONCLUSIONS: PCT is a more sensitive and specific predictor of MCD than CRP and WCC in children presenting with fever and a rash.

Adolescent↗
PubMed2002

Improved case confirmation in meningococcal disease with whole blood Taqman PCR.

BACKGROUND: The clinical diagnosis of meningococcal disease (MCD) can be difficult. Non-culture methods like the previous ELISA meningococcal PCR improved case confirmation rates, but were not ideal. A Taqman meningococcal PCR, using DNA extracted from serum (S-Taqman), which has an improved sensitivity compared to the ELISA method in vitro, was introduced into clinical practice in July 1997. A new whole blood DNA extraction method for Taqman (WB-Taqman) was introduced in September 1999. AIMS: To determine the degree of improvement in the confirmation rate in clinically diagnosed MCD, following the introduction of WB-Taqman. METHODS: A total of 192 patients (WB-Taqman) with possible or probable MCD, including those admitted to our paediatric intensive care unit, were studied. Admission EDTA samples obtained were sent for bacterial DNA detection at the Meningococcal Reference Unit (MRU), Manchester. These patients were compared to 319 patients with possible and probable MCD, seen at the same hospital prior to the introduction of WB-Taqman. RESULTS: Following the introduction of WB-Taqman, 82 of the 95 probable cases (88%) had a positive meningococcal PCR result. This gives a diagnostic sensitivity and specificity for WB-Taqman of 87% and 100% respectively. Following WB-Taqman all blood culture positive patients were also PCR positive. Confirmation of cases by PCR rose from 47% (S-Taqman, n = 166) to 88% (WB-Taqman). When all confirmatory tests were included, case confirmation increased from 72% (S-Taqman) to 94% (WB-Taqman). CONCLUSION: The sensitivity of PCR in confirming clinical MCD has improved significantly with this new method. The gold standard for confirming cases of MCD is now the WB-Taqman PCR.

Bacteriological Techniques↗
PubMed2001

Non-pulmonary tuberculosis.

Tuberculosis (TB) is a serious disease of global importance, with a rising incidence in the developed world in recent years. Tuberculous lymphadenitis, tuberculous meningitis, osteoarticular tuberculosis and miliary tuberculosis are some of the more well-recognised manifestations of non-pulmonary TB in childhood. The diagnosis of non-pulmonary TB poses a particular challenge for clinicians because of the protean ways in which the disease presents. The omission of tuberculosis from the differential diagnosis of patients with obscure illnesses and the relatively insensitive bacteriological methods for detecting Mycobacterium tuberculosis add to the complexity of the problem. A high index of suspicion is required in order to avoid delays in diagnosis which may influence treatment outcome. The advent of DNA amplification techniques such as the polymerase chain reaction may herald a promising new era in the prompt and accurate management of extrapulmonary tuberculosis.

Adolescent↗
PubMed2001

New therapies and vaccines for meningococcal disease.

Meningococcal disease (MCD) is an important cause of morbidity and mortality. The pathophysiology consists of a complex interaction of bacterial and host factors, triggered by the release of endotoxin which initiates the inflammatory cascade, resulting in multi-organ failure, coagulopathy, capillary leak, metabolic derangement and eventually death. Prompt recognition and aggressive management are essential in reducing mortality. Over the past decade, there has been intense research into novel therapies and vaccines, with largely disappointing results. Therapies have been broadly divided into anti-endotoxin and anti-TNF-alpha therapies, treatment aimed at correcting coagulopathy and at blood purification and anti-inflammatory cytokine therapy. The reasons for the disappointing results in the search for new therapeutic strategies are difficult to identify. The disordered physiology in MCD results from a complex interaction of several mediators; therefore attempts to correct this by altering just one step represents a gross oversimplification of the process. In addition, the experimental model of endotoxaemia, which is often used, is a poor representation of an acutely ill patient with rapidly progressive shock. There have been several small or poorly designed trials, which have failed to reach definite conclusions. In order to yield conclusive results any future trials must be multicentre, randomised, controlled trials, but these are expensive and, in practice, difficult to conduct. The BPI trial (vide infra) was a significant step forward in this regard and demonstrated the ability to organise a large multicentred trial which can act as a template for future trials. Although the results were not significant there was an overall trend towards improved outcome in the treatment arm. Whilst the development of effective therapies and vaccines are awaited, the priorities at present must be the prompt recognition and aggressive management of disease.

Animals↗
PubMed2000

The role of RANTES in meningococcal disease.

The chemokine RANTES (regulated on activation, normal T cell expressed and secreted) is a potent regulator of leukocyte trafficking. RANTES preferentially attracts mature CD4 cells as well as macrophages and eosinophils, but not neutrophils. In total, 128 children with meningococcal disease were prospectively studied, and the role of RANTES in the pathophysiology of meningococcal disease was assessed. Plasma RANTES, interleukin (IL)-8, IL-6, IL-1 receptor agonist, and tumor necrosis factor-alpha were measured at admission. Severity of disease was stratified by the Glasgow meningococcal septicemia prognostic score (GMSPS). RANTES levels correlated significantly with IL-8 levels, admission lactate levels, platelets, prothrombin time, and activated partial thromboplastin time. RANTES levels were lower in children with severe disease (GMSPS>/=8; P=.001), in those with septic shock (P<.0005), and in nonsurvivors (P=.048; Mann-Whitney test). RANTES is a potential mediator in the pathophysiology of meningococcal disease.

Adolescent↗
PubMed2000

Increasing microbiological confirmation and changing epidemiology of meningococcal disease on Merseyside, England.

OBJECTIVES: To determine, for the last 5 years in children on Merseyside with clinical meningococcal disease (MCD), the impact on diagnostic yield of newer bacteriologic methods; bacterial antigen detection (AD) and polymerase chain reaction (PCR). METHODS: Prospective data collection at Royal Liverpool Children's Hospital over two epochs: 1 September 1992 to 30 April 1994 (epoch A, n = 126) and 17 November 1997 to 15 September 1998 (epoch B, n = 85). RESULTS: Epoch A was compared with epoch B. Diagnosis was confirmed by detection of meningococci in 78 of 126 (61.9%) versus 64 of 85 (75.3%, P = 0.04), but with a significantly lower rate of positive blood and cerebrospinal fluid culture in the later epoch. The proportion of cases receiving penicillin pretreatment was unchanged at 32%, but the proportion undergoing lumbar puncture decreased significantly. Median ages were higher in epoch B: 1.7 years versus 2.49 years (P = 0.013, Mann-Whitney). There was a significant increase in the proportion of cases due to serogroup C (14/78 (18%) versus 30/64 (46.9%), P = 0.001). CONCLUSIONS: Culture detection of meningococci from children with MCD has reduced, as less lumbar punctures are done. However, improved diagnosis by PCR and AD has increased microbiological confirmation overall. Serogroup C disease and the median age of cases continue to rise.

Adolescent↗
PubMed2000

Performance characteristics of the polymerase chain reaction assay to confirm clinical meningococcal disease.

BACKGROUND: Confirmation of clinical meningococcal disease (MCD) is essential for management of patients, contacts, and outbreaks. Blood and CSF cultures, the traditional gold standard diagnostic tests, have been adversely affected by preadmission parenteral penicillin and fewer lumbar punctures. Rapid, reliable serogroup determination without the need to grow isolates could improve laboratory confirmation of MCD. AIMS: To determine performance characteristics of the currently available meningococcal polymerase chain reaction (PCR) assays in a clinical setting. METHODS: Prospective study of 319 children presenting with a suspected diagnosis of MCD (fever and a rash, or suspected bacterial meningitis) over a 16 month period. RESULTS: A total of 166 (52% of all) children had clinical MCD: diagnosis was confirmed microbiologically in 119 (72%) of these. Performance characteristics (sensitivity, specificity, negative predictive value, positive predictive value) in confirmation of clinical MCD were respectively (95% confidence interval): blood culture 31% (24-38%), 100%, 57% (49-65%), 100%; blood PCR 47% (39-55%), 100%, 65% (58-73%), 100%; any test positive 72% (65-79%), 100%, 77% (70-84%), 100%. CONCLUSIONS: Meningococcal DNA detection in blood or CSF by PCR is a useful method of diagnosis of MCD. PCR of peripheral blood performs better than blood culture. In a child with clinically suspected MCD, PCR assays, bacterial antigen tests, and oropharyngeal swabbing for meningococcal carriage should be performed in addition to blood or CSF culture, to improve case confirmation.

Antigens, Bacterial↗
PubMed1996

Congenital lobar emphysema in congenital cytomegalovirus infection.

We report a case of congenital lobar emphysema diagnosed antenatally in an infant of 32 weeks' gestation. Histology and serology confirmed infection with cytomegalovirus (CMV). CMV pneumonitis leading to inflammation and obstruction in the bronchial tree may have resulted in the development of congenital lobar emphysema.

Adult↗
PubMed1988

Detection of estrogen receptor proteins in breast tumors using an improved APAAP immunohistochemical technique.

A monoclonal antibody (anti-estrogen receptor [ER] from the ER-immunocytochemical assay [ICA] [Abbott Laboratories, Berkshire, England]), which binds to epitopes of the estrogen receptor in surgical biopsy specimens of breast carcinomas, was used in an improved alkaline phosphatase anti-alkaline phosphatase (APAAP) technique for in-situ receptor detection. This method was compared with a standard radioligand binding biochemical assay in assessing the ER status of 48 human breast carcinomas. The monoclonal antibody allowed detection of ER in the presence of estrogens or anti-estrogens and avoided problems of nonspecific intrinsic reactions, due to endogenous steroid hormones. The immunohistologic results (positive and negative) correlated well with the radioligand binding results (rs = 0.760; P less than 0.001) and allowed the additional assessment of cell morphology and tumor heterogeneity in the cryostat sections. The APAAP method provides diagnostic rapidity (approximately 4 hours) combined with sensitivity as compared with the radioligand assay (an approximately 2-day assay). The vivid red color associated with APAAP staining also was a distinct advantage compared with the brown reaction product of ER-ICA in interpreting stained sections. The results of this study indicate that the APAAP technique is an improved method for detection of ER and is applicable in routine hospital practice, thereby contributing to the immediate clinical management of patients with breast tumors.

Alkaline Phosphatase↗