Which symptoms and clinical features correctly identify serious respiratory infection in children attending a paediatric assessment unit?

OBJECTIVE: Parent-reported symptoms are frequently used to triage children, but little is known about which symptoms identify children with serious respiratory infections. The authors aimed to identify symptoms and triage findings predictive of serious respiratory infection, and to quantify agreement between parent and nurse assessment. DESIGN: Prospective diagnostic cohort study. SETTING: Paediatric Assessment Unit, University Hospitals Coventry and Warwickshire NHS Trust. PATIENTS: 535 children aged between 3 months and 12 years with suspected acute infection. METHODS: Parents completed a symptom questionnaire on arrival. Children were triaged by a nurse, who measured routine vital signs. The final diagnosis at discharge was used as the outcome. Symptoms and triage findings were analysed to identify features diagnostic of serious respiratory infection. Agreement between parent and triage nurse assessment was measured and kappa values calculated. RESULTS: Parent-reported symptoms were poor indicators of serious respiratory infection (positive likelihood ratio (LR+) 0.56-1.93) and agreed poorly with nurse assessment (kappa 0.22-0.56). The best predictor was clinical assessment of respiratory distress (LR+ 5.04). Oxygen saturations <94% were highly specific (specificity 95.1%) but had poor sensitivity (35.6%). Tachypnoea (defined by current Advanced Paediatric Life Support standards) offered little discriminatory value. CONCLUSION: Parent-reported symptoms were unreliable discriminators of serious respiratory infection in children with suspected acute infection, and did not correlate well with nurse assessment. Using symptoms to identify higher risk children in this setting is unreliable. Nurse triage assessment of respiratory distress and some vital signs are important predictors.

Views on personalized medicine: do the attitudes of African American and white prescription drug consumers differ?

AIMS: Although recent advances in pharmacogenomics are making possible the use of genetic testing to determine the best medication for patients, little is known about how patients view such procedures. The aims for this study that were developed collaboratively as part of a community-academic partnership are: (1) What are the attitudes and perceptions of prescription drug consumers concerning personalized medicine and genetic testing for drug compatibility and how do they differ between African American and white patients? (2) What are the attitudes and perceptions of patients concerning race-based prescribing and how do they differ between African American and white patients? METHODS: We conducted 6 focus groups, 2 with white participants and 4 with African American participants. Focus groups were audio-recorded, transcribed, and analyzed to ascertain common themes. RESULTS: Our results suggest that personalized medicine and genetic testing, though not well understood by lay persons, were considered positive advances in medicine. However, participants also voiced concerns about these advances that differed by race. CONCLUSION: This study points to the need to include perspectives of at-risk communities as we move toward wider use of this technology.

How well do vital signs identify children with serious infections in paediatric emergency care?

OBJECTIVES: To determine whether vital signs identify children with serious infections, and to compare their diagnostic value with that of the Manchester triage score (MTS) and National Institute for Health and Clinical Excellence (NICE) traffic light system of clinical risk factors. DESIGN: Prospective cohort of children presenting with suspected acute infection. We recorded vital signs, level of consciousness, activity level, respiratory distress, hydration and MTS category. SETTING: Paediatric assessment unit at a teaching hospital in England. PARTICIPANTS: 700 children (median age 3 years), of whom 357 (51.0%) were referred from primary care, 198 (28.3%) self-referrals and 116 (16.6%) emergency ambulance transfers. Just over half (383 or 54.7%) were admitted. MAIN OUTCOME MEASURES: Severity of infection categorised as serious, intermediate, minor or not infection. RESULTS: Children with serious or intermediate infections (n = 313) were significantly more likely than those with minor or no infection (n = 387) to have a temperature >or=39 degrees C, tachycardia, saturations 2 seconds. Having one or more of temperature >or=39 degrees C, saturations

Acute disseminated encephalomyelitis: a review of 18 cases in childhood.

OBJECTIVE: Acute disseminated encephalomyelitis (ADEM) is a treatable inflammatory demyelinating disorder seen more commonly in children than in adults. It typically presents to general paediatricians, often, like encephalitis, with non-specific cerebrospinal fluid findings. The brain computerized tomography scan is usually normal, so is falsely reassuring and delays the diagnosis, which might result in considerable morbidity. The present study was initiated to report on the various modes of presentation and raise the awareness of the diagnosis of ADEM among general paediatricians. METHODS: A retrospective review of the case notes of 18 children with a diagnosis of ADEM established in a tertiary referral centre from 1995 to 2000 was undertaken with particular reference to clinical features, investigations and treatment. RESULTS: The most common presenting features were ataxia (10 cases), followed by headache (eight cases) and weakness (five cases). Magnetic resonance imaging (MRI) of the brain was needed to confirm the diagnosis in all 18 children. Treatment usually included a course of intravenous methylprednisolone followed by a tapering dose of oral prednisolone over several weeks. Although the outcome for most of the children was generally good, two relapsed after cessation of steroids and five children had ongoing disabilities. CONCLUSIONS: The investigation of choice for establishing the diagnosis of ADEM was MRI of the brain. Other investigations were seldom helpful in reaching the diagnosis. Early diagnosis and prompt treatment of ADEM will probably reduce morbidity.

Analysis of ploidy and proliferative activity in childhood non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD).

We have performed DNA analysis by means of fluorescence-activated cell cytometry on paraffin-embedded tissue from the diagnostic biopsy specimens in 40 cases of non-Hodgkin's lymphoma (NHL) and 25 of Hodgkin's disease (HD) and from 50 normal tonsils as controls. For HD cases, aneuploidy was found in 7 of 25 (28%), a higher proportion than in two previous studies of mainly adult patients. Diploid tumors showed S-phase fractions (SPFs) similar to those of controls. In the NHL cases aneuploidy was found in 12 of 40 (30%) with no significant association with site, stage, histopathology, immunophenotype, or prognosis. SPFs were highest in abdominal and chest primary sites but were not related to stage. Burkitt's lymphomas had the highest SPFs relative to lymphoblastic (P < .01) and centroblastic lymphomas (P < .05). Significantly higher SPFs were found in B cell than in T cell tumors (P < .001). There was considerable heterogeneity for SPFs within each NHL subgroup. Survival was worse at 5 years for those with high SPFs compared with those with normal SPFs (P = .04). These results suggest that tumor DNA analysis may be useful in the evaluation of children with NHL. Larger studies are needed to define its role as an independent prognostic variable.

Immunophenotypic analysis of childhood Burkitt's lymphoma in the West Midlands 1957-1986.

AIMS: To analyse the immunophenotype of a large number of non-endemic Burkitt's lymphomas to determine whether a B cell phenotype is consistently recognisable using formalin fixed, paraffin wax embedded archival material and a standard panel of commercially available antibodies. METHODS: Archival material was obtained from 30 cases of childhood Burkitt's lymphoma registered with the West Midlands Regional Children's Tumour Research Group. These were analysed by a standard avidin biotin complex immunoperoxidase method using antibodies to CD45, CD43, CD30, CD20, CD15, and immunoglobulin heavy and light chains. RESULTS: There was a high incidence of the CD45RB and CD20 immunophenotypes, with a clearly recognisable B cell lineage even in archival material. IgM was identifiable in 13 of the 23 (56.5%) cases tested. Only three of 17 (18%) cases expressed CD30. Positive membrane staining with CD45RO was observed in two (6.7%) cases. CONCLUSIONS: A B cell lineage can be identified in Burkitt's lymphoma in formalin fixed, paraffin wax embedded material, even in archival tissue. There was a low incidence of membrane staining with CD45RO which is a potential source of diagnostic confusion.

Hodgkin's disease in children in the West Midlands, 1957-1986: a large population-based study.

One hundred forty-one children were diagnosed with Hodgkin's disease between 1957 and 1986 in the West Midlands Health Authority Region (1991 population, 1.1 million children). Eighty-seven were boys and 54 were girls, representing a significant male:female ratio of 1.5:1 (P < 0.01). The average age-standardized incidence rate was 3.6 per million per year with a significant increase in the older age group (> or = 10 years) in the second half of the period (P = 0.02). The mixed cellularity subtype was more common in those younger than 10 years, with nodular sclerosing disease being seen more in those < or = 10 years. Overall survival at 5 years was 76% (65% at 10 years) with a significant difference (P < 0.001) in survival between the first and last decades. There was six second malignancies, five of which could have been treatment related. A positive history of cancer in close relatives was found in 11 patients, and higher social class was found in more older than younger children. These findings support the hypothesis that Hodgkin's disease may have a viral etiology and may be linked with socioeconomic conditions.

Parental imprinting of human chromosome region 11p15.3-pter involved in the Beckwith-Wiedemann syndrome and various human neoplasia.

Cytogenetic and DNA analyses of patients with the Beckwith-Wiedemann syndrome (BWS) enabled us to refine the localization of the syndrome at 11p15.3-pter to two distinct regions. One chromosome region (BWSCR1) is near the insulin (INS) and insulin-like growth factor 2 (IGF2) genes. The other region (BWSCR2) is more proximal near two sequences with zinc-binding finger motifs and a number of known and putative genes. This latter region, at least, seems to be associated with the development of childhood tumors. Our results strongly support the proposed involvement of parental imprinting in the etiology of BWS since all balanced chromosomal abnormalities in these patients were maternally transmitted while the mothers were phenotypically normal. We demonstrate that such an autosomal balanced rearrangement can lead to a specific maternal hypomethylation of the INS/IGF2 genes localized distal to the breakpoint. This underlines the role of these genes in the etiology of the syndrome.

Epstein-Barr virus (EBV) and Hodgkin's disease in children: incidence of EBV latent membrane protein in malignant cells.

Previous studies have detected EBV DNA by Southern blotting or in situ hybridization in biopsy material from up to 30 per cent of adult cases of Hodgkin's disease. Here we have used monoclonal antibodies specific for the EBV latent membrane protein LMP1 to examine archival material from children with Hodgkin's disease. Material from 74 cases (54 males and 20 females) was examined and 37 (30 males and 7 females) were classified as LMP1-positive in the malignant cells. LMP1 positivity was present in 4/13 (31 per cent) of lymphocyte predominant, 14/36 (39 per cent) of nodular sclerosis, 17/20 (85 per cent) of mixed cellularity, 1/2 (50 per cent) of lymphocyte depletion, and 1/3 (33 per cent) of unclassified subtypes. The positive cases by clinical stage were I 9/22 (41 per cent), II 9/20 (45 per cent), III 11/24 (46 per cent), and IV 8/8 (100 per cent). LMP1 positivity was present in 2/5 (40 per cent) children aged less than 5 years, 12/27 (44 per cent) aged 5-10 years, and 23/42 (48 per cent) aged between 10 and 15 years. The association between EBV and Hodgkin's disease in children thus appeared to be more frequent in patients with mixed cellularity and advanced disease, but examples of EBV-positive tumours were found in all histological subtypes, stages, and ages. Stepwise discriminant function analysis showed that clinical stage IV and mixed cellularity histology are independently associated with LMP1 positivity. These observations indicate that Hodgkin's disease in children is at least as strongly linked to EBV as is the disease in adults.

Post-operative analgesia following femoral-neck surgery--a comparison between 3 in 1 femoral nerve block and lateral cutaneous nerve block.

A prospective controlled randomized trial on patients receiving surgery for fractured neck of femur was carried out, in which post-operative analgesic requirements in three separate groups were compared. Patients in Group 1 acted as controls, whilst those in Groups 2 and 3 received lateral cutaneous nerve blocks and 3 in 1 femoral nerve blocks, respectively. Patients in Group 3 needed significantly less analgesia than the other two groups, and the time to first administration of analgesia was significantly longer. No complications of either of the nerve blocks was noted.

Changes in the postenteropathic form of the hemolytic uremic syndrome in children.

An analysis was made of clinical and laboratory findings in children with the diarrheal form of the hemolytic uremic syndrome (HUS) treated at The Children's Hospital, Birmingham between 1970 und 1987. From 1982 the rate of referral increased, the prodromal illness more often consisted of bloody diarrhea, and the mean age at presentation doubled from 2 to 4 years. For patients with a good outcome there was an excess of males in the period 1970-81, and females in the period 1982-87. Moreover, in the years 1982-87 the disorder was distinguished from that of the earlier time by a positive correlation between adverse outcome and both neutrophil leukocytosis and a higher hemoglobin concentration at presentation. Prognostic scores obtained by logistic regression analysis were specific for each period. From July 1983 stool samples were analyzed for verocytotoxin-producing Escherichia coli (VTEC) and neutralizable verotoxin. Positive results were obtained in 39% of cases. The nature of HUS has changed and the new form of the disorder is associated with VTEC infection.

Guillain-Barré syndrome mimicking brainstem death.

There must be a defined, predisposing condition to fulfil the criteria of brainstem death in the UK. A patient presented recently in coma and with absent brainstem reflexes, but no diagnosis was initially obvious. A subsequent diagnosis of Guillain-Barré syndrome was made, and the patient made a full recovery.

The clinical significance of the glomerular location of segmental lesions in focal segmental glomerulosclerosis.

Serial sections of renal biopsies obtained from 44 nephrotic children with focal segmental glomerulosclerosis (FSGS) were reviewed in order to determine the glomerular location of segmental lesions and relate the findings to the outcome of illness. There were 23 boys and 21 girls aged 0.9-14.2 years at onset. FSGS was classified as "hilar" in biopsies containing at least one lesion contiguous with or involving the hilum, regardless of the location of other lesions, and as "peripheral" in the absence of hilar lesions. Of the 44 initial biopsies, 33 were designated hilar and 6 peripheral; the remaining 5 were unclassifiable as it was not possible to determine the location of 1-3 lesions in each biopsy. Twenty-eight of the 33 hilar biopsies also contained peripheral lesions, including paratubular (glomerular "tip") lesions in 15 instances. Paratubular lesions as the predominant abnormality were observed in only four biopsies. Repeat biopsies showed that transition occurred from one type to another, and only 4 biopsies remained with a final designation of peripheral FSGS. After a follow-up period of 1.6-24.9 years (mean 9.3), there was no significant difference in outcome between hilar and peripheral FSGS, whether diagnosed on the initial or repeat biopsy. The division into separate categories is not clearcut, and the use of this as a prognostic aid does not justify the additional cost of preparing and examining numerous serial sections.

The M1 air crash. The demands placed on anaesthetic and intensive care services of two hospitals.

The M1 air crash provided an enormous challenge to the anaesthetic and intensive care services of the hospitals which admitted the survivors, many of whom had serious injuries. This account describes some of the problems which were encountered in two of the hospitals, details the workload imposed on the anaesthetists and the staff of the Intensive Therapy Units and identifies factors which, if improved, might advance the management of multiple casualties admitted from the scene of a major disaster.

Caudal anaesthesia for postoperative pain relief in children: a comparative trial of different regimens using plain bupivacaine.

A comparative trial between three different dosage regimens of bupivacaine administered by the caudal route, used for the prevention of postoperative pain in children undergoing elective inguinal herniotomy or ligation of patient processus vaginalis was undertaken. The regimens compared were bupivacaine 0.25% (1 ml/kg), bupivacaine 0.25% or 0.5%: (Age (years +2)/10 ml per dermatome to be blocked. This being calculated for inguinal surgery to be Age (years) + 2 ml. A linear analogue pain scale was used to evaluate pain, all three regimens being found to produce excellent analgesia, there being no significant difference between the pain scores of the three groups. Time to onset of analgesia, as indicated by changes in intraoperative heart rate in response to surgical stimulation were also similar in all groups. No evidence of postoperative motor weakness or disturbance of bladder function was found and there were no symptoms or signs attributable to local anaesthetic toxicity.

Molecular nature of genetic changes resulting in loss of heterozygosity of chromosome 11 in Wilms' tumours.

In this paper we describe the analysis of genetic changes in chromosome 11 in Wilms' tumours. Using a range of probes for regions 11p15, 11p13 and 11q we have screened DNA from 14 Wilms' tumours together with control DNA obtained from the patients' lymphocytes and their parents. We have been able to demonstrate loss of heterozygosity in 5 of the 14 different Wilms' tumours. In three of these five tumours, loss of heterozygosity did not involve markers for 11p13, 11p15.4 or the proximal region of 11p15.5, but only some markers assigned to the most distal part of 11p15.5. In two of these tumours we could demonstrate unequal mitotic recombination in 11p with breakpoints in the hypervariable regions 5' of the insulin gene and/or 3' of the HRASI proto-oncogene. In one tumour, from a Beckwith-Wiedemann patient, all markers for the region 11q13-pter became hemizygous; the region 11q13-qter remained heterozygous. These results demonstrate that loss of heterozygosity in Wilms' tumours may not necessarily involve the proposed Wilms' tumours locus at 11p13 but may be limited to 11p15.5. This suggests that not only the 11p13 region, but also the 11p15.5 region is involved in Wilms' tumour development. The possible role of both regions in the development of Wilms' tumour is discussed.