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Biomedical subjects

F A Riordan

Publications and source records attributed to F A Riordan.

At least 19 recordsLinked to original sources
PubMed2001

Improving promptness of antibiotic treatment in meningococcal disease.

OBJECTIVES: Delays in parenteral antibiotic treatment may contribute to the high mortality in meningococcal disease. This study aimed to record "door to needle" time in children with meningococcal disease before and after the introduction of a specific teaching programme about the disease. METHODS: "Door to needle" time in 33 children with meningococcal disease, admitted June 1995-December 1996, were studied. Regular teaching sessions encouraging prompt treatment were started in January 1997. "Door to needle" time was then studied for 42 children admitted January 1997-December 1998. RESULTS: More of the second cohort attended accident and emergency (A&E) directly (9 of 33 v 24 of 42; p=0.01) rather than being referred by a GP. Similar proportions received pre-admission antibiotics from a GP (8 of 24 v 5 of 18). Mortality was similar in the two groups (2 of 33 v 5 of 42). "Door to needle" time was significantly shorter in the second cohort in those with a typical rash (median 60 minutes v 18 minutes; p=0.0004). Only 1 of 23 (4%) children in the second cohort with a typical, petechial rash waited more than 60 minutes for antibiotics, compared with 6 of 24 in the first cohort (p=0.06). CONCLUSIONS: Significant improvements in "door to needle" time in meningococcal disease can be achieved when awareness is heightened by regular teaching. Those with a typical, petechial rash can be treated within 60 minutes of arrival. Strategies to improve immediate treatment of meningococcal disease should include education of A&E staff, especially as an increasing proportion of cases present directly to A&E.

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

Do presenters to paediatric meetings get their work published?

BACKGROUND: Research presented to a scientific meeting is inaccessible to clinicians, unless it is also published in a cited journal. AIMS: To assess the publication rate of studies presented to two UK national paediatric meetings: the Paediatric Research Society (PRS) and the British Paediatric Association (BPA). METHODS: A Medline search in December 1999 for the first authors of all plenary abstracts presented in 1996. If not found, authors contacted by postal questionnaire. RESULTS: Information was obtained on 88/89 presentations. Twenty five of 48 PRS and 31 of 40 BPA studies were published in Medline listed journals. The major reason for non-publication was that they had not been submitted (PRS 15/48, BPA 6/40). Some authors were still hoping to do so (PRS 7, BPA 2). Other reasons were: publication in other forms (theses, book chapters, non-Medline journals) (PRS 5, BPA 2), or still being reviewed (PRS 3, BPA 1). Ten of 11 randomised, controlled trials were published, but only 20 of 37 observational studies were submitted and published. CONCLUSION: Presenters to paediatric meetings need help in submitting and publishing their work.

Child↗
PubMed1999

Ceramide-induced killing of normal and malignant human lymphocytes is by a non-apoptotic mechanism.

Synthetic ceramides induce apoptotic death of Jurkat and HL60 leukaemia cell lines. By contrast we show here that ceramide induces non-apoptotic killing of malignant cells from patients with B-chronic lymphocytic leukaemia (B-CLL) and of normal B lymphocytes. The protein phosphatase inhibitor okadaic acid readily induces apoptosis of B-CLL cells, indicating that this death pathway is fully functional in these cells. The ability of ceramide to activate the apoptotic protease caspase 3 in HL60 cells but not in B-CLL cells, as well as the lack of correlation of ceramide-mediated killing of different B-CLL isolates with expression of the apoptosis-regulating proteins bcl-2 and bax reinforce the conclusion that ceramide killing of B-CLL cells is by a non-apoptotic mechanism. Fludarabine treatment or gamma-irradiation of B-CLL cells resulted in ceramide elevation and in killing by both apoptotic and non-apoptotic mechanisms, suggesting that a ceramide-triggered non-apoptotic mechanism may play a role in the killing of these cells. Therefore, the results here show that ceramide can induce either apoptotic or non-apoptotic death, depending on the cellular context. The inability of synthetic dihydroceramide to kill B-CLL cells or normal B lymphocytes suggests that non-apoptotic killing by ceramide is via interaction with a specific, but unidentified, cellular target.

Amidohydrolases↗
PubMed1999

Admission cortisol and adrenocorticotrophic hormone levels in children with meningococcal disease: evidence of adrenal insufficiency?

OBJECTIVE: To measure admission cortisol and adrenocorticotrophic hormone (ACTH) levels in children with meningococcal disease to try and determine the prevalence of adrenal insufficiency. DESIGN: Prospective observational study. SETTING: Pediatric departments of four hospitals in Merseyside, United Kingdom. PATIENTS: Ninety-six children with meningococcal disease; 29 with hypotension, ten of whom died. MEASUREMENTS AND MAIN RESULTS: Admission cortisol, ACTH, and proinflammatory cytokine levels were measured. Serial cortisol levels also were measured during the first 48 hrs. Significantly lower cortisol levels were found in those who died compared with survivors. Significantly higher ACTH levels also were found in those who died. However, no child had a cortisol level <5 microg/dL (<138 nmol/L) implying definite adrenal insufficiency. Three of 29 children with hypotension had plasma cortisol levels implying possible adrenal insufficiency (<18 microg/dL [<497 nmol/L]), but high ACTH levels were only found in one of those three. Cortisol levels decreased significantly after antibiotic treatment, unless steroid therapy was administered. ACTH levels did not correlate with cortisol or proinflammatory cytokine levels. CONCLUSIONS: Children with meningococcal disease have a wide range of initial plasma cortisol levels, with lower levels found in those who die. Many factors may affect cortisol levels, but adrenal insufficiency is probably uncommon.

Adolescent↗
PubMed1999

Endothelial cell adhesion molecules in meningococcal disease.

BACKGROUND: Endothelial damage is important in meningococcal disease. Cell adhesion molecules, including P selectin, E selectin, and intercellular cell adhesion molecule 1 (ICAM-1), are expressed by activated endothelium and then subsequently shed. METHODS: ICAM-1, P selectin, and E selectin were measured on admission to hospital in children with meningococcal infections. RESULTS: Concentrations of shed cell adhesion molecules are reported for 78 children. Eleven did not have meningococcal disease. Of the 67 with meningococcal disease, 40 had mild disease (Glasgow meningococcal septicaemia prognostic score (GMSPS) < 8) and 27 had severe disease (GMSPS > or = 8). E selectin and ICAM-1 values were higher in those with meningococcal disease. The E selectin values in those with severe disease were higher than in those with mild disease. P selectin concentrations were not altered in meningococcal disease, but those who died had lower concentrations. CONCLUSIONS: Endothelial activation in meningococcal disease is reflected by shed ICAM-1 and E selectin concentrations.

Adolescent↗
PubMed1998

Okadaic acid-induced apoptosis of HL60 leukemia cells is preceded by destabilization of bcl-2 mRNA and downregulation of bcl-2 protein.

We have studied the actions of the protein phosphatase inhibitor okadaic acid (OA) on the expression of bcl-2 in HL60 human leukemia cells. OA induced downregulation of bcl-2 mRNA and protein prior to the induction of apoptosis. Downregulation of bcl-2 mRNA levels did not result from actions of OA on the bcl-2 upstream negative response element. Nuclear run-off analyses confirmed that OA did not affect bcl-2 gene transcription. However, OA caused a rapid increase in the rate of degradation of bcl-2 mRNA. Therefore, OA induces down-regulation of bcl-2 expression via destabilization of its transcript. The constitutive action of an OA-sensitive protein phosphatase may therefore maintain HL60 cell survival by blocking bcl-2 mRNA degradation.

Apoptosis↗
PubMed1998

Herbimycin A accelerates the induction of apoptosis following etoposide treatment or gamma-irradiation of bcr/abl-positive leukaemia cells.

Philadelphia chromosome (Ph)-positive leukaemia cells express the chimeric bcr/abl oncoprotein, whose deregulated protein tyrosine kinase (PTK) activity antagonizes the induction of apoptosis by DNA damaging agents. Treatment of Ph-positive K562, TOM 1 and KCL-22 cells with etoposide for 2d induced cytosolic vacuolation, but not nuclear condensation or DNA fragmentation. The bcr/abl kinase-selective inhibitor herbimycin A increased the induction of nuclear apoptosis by etoposide or gamma-radiation. The concentration of herbimycin required to synergize with etoposide was similar to that required to decrease the level of tyrosine phosphorylated proteins or of the protein tyrosine kinase activity of anti-abl immune complexes in K562 cells. The ability of herbimycin A to sensitize K562, TOM 1 or KCL-22 cells to apoptosis induction correlated with its ability to decrease the cellular content of phosphotyrosyl proteins in these Philadelphia-positive lines. Enhancement of nuclear apoptosis by herbimycin was not attributable to downregulation of the bcl-2 or bcl-XL anti-apoptotic proteins. In contrast, herbimycin protected Philadelphia-negative HL60 cells from apoptosis induction by etoposide and did not affect killing of NC37 and CEM cells. The data suggest that the induction of apoptosis is blocked in cells expressing the bcr/abl oncoprotein and that herbimycin A increases induction of programmed cell death following DNA damage. Selective PTK inhibitors may therefore be of value in securing the genetic death of Ph-positive leukaemia cells.

Antibiotics, Antineoplastic↗
PubMed1998

Prospective study of "door to needle time" in meningococcal disease.

OBJECTIVE: To measure the promptness of antibiotic treatment in children with meningococcal disease. METHODS: "Door to needle time" for parenteral antibiotics in children with meningococcal disease was recorded prospectively as part of a larger study. The time from arrival at hospital until the first dose of parenteral antibiotics was recorded in 100 children with meningococcal disease (median (range) age 21 (3-168) months) admitted to four Merseyside hospitals. RESULTS: Forty five children presented directly to the accident and emergency (A&E) department. Parenteral penicillin was given before admission to 19 of the 55 children referred by general practitioners (GPs). Median door to needle time was 36 minutes. All children with a typical petechial rash on arrival received antibiotics within 60 minutes. Antibiotics were given sooner to those with severe disease (p = 0.01) and later to those without a rash (p = 0.007). CONCLUSIONS: The first dose of parenteral antibiotics for most children with meningococcal disease was given in A&E. When awareness of meningococcal disease is heightened by ongoing research, those with a petechial rash are treated within 60 minutes. Strategies to improve immediate treatment of meningococcal disease should include education of A&E staff as well as GPs.

Adolescent↗
PubMed1998

Imported infections in east Birmingham children.

This 15-month prospective study of admissions to a children's ward found imported infections in 58 children (1.3% of admissions), aged between two months and 15 years. Most had visited the Indian subcontinent 14 (1-341) days earlier. Few had taken preventative measures. The commonest infection was malaria (n = 23).

Adolescent↗
PubMed1997

Plasma fibronectin levels in meningococcal disease.

UNLABELLED: Fibronectin (a glycoprotein which modulates inflammation) may decrease mortality in systemic infection. Children with meningococcal disease (MCD) may have low fibronectin levels. We aimed to compare plasma fibronectin levels in children with MCD and controls, correlate fibronectin levels with interleukin-6 (IL-6), shock and death, and assess fibronectin as an aid to early diagnosis in MCD. Samples were taken on admission from 99 children with MCD and 49 controls. Plasma fibronectin was measured using a turbidimetric immunoassay. Plasma fibronectin was significantly lower in MCD compared to controls (57 micrograms/ml vs 105 micrograms/ml; P < 0.005). Children who died had significantly lower levels than survivors (29 micrograms/ml vs 62 micrograms/ml; P = 0.01). Fibronectin levels were negatively correlated with IL-6 levels. Fibronectin was a poor predictor of MCD. CONCLUSION: Plasma fibronectin levels are decreased in children with MCD, especially in shock and death. This decrease is associated with high IL-6 levels. Fibronectin could be a novel therapy in severe MCD.

Biomarkers↗