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Aims—To examine the clinical and biological features of acute lymphoblastic leukaemia in children with Down’s syndrome (DS), to compare their survival with other children, and to determine if entry to trials and survival has improved. Methods—Examination of presenting features and response to treatment in patients treated in two consecutive national trials, MRC UKALL X and XI. Results—The proportion of children with DS was significantly higher in UKALL XI (1.9%) than UKALL X (0.9%). Children with DS tended to be under 10 years and to have the common ALL subtype. Cytogenetic analysis showed that favourable features, such as high hyperdiploidy and t(12;21) were less frequent but also that there was a lack of translocations associated with a poor prognosis. Children with DS showed no increase in risk of relapse at any site but their survival and event free survival were inferior to other children. These results were caused by an increased number of infective deaths during remission (11% compared to 2%). At five years overall survival was 73% in DS children compared with 82% in other children; event free survival was 53% compared to 63% in non-DS children. Conclusions—Entry of children with DS to national trials has increased and survival has improved. However they remain at risk of relapse and also of treatment related mortality. These findings emphasise the need for both intensive chemotherapy and optimal supportive care. (Arch Dis Child 2001;85:321‐325)

BACKGROUND—Fine needle aspiration biopsy (FNA) is a routine diagnostic technique for evaluating thyroid nodules. Many reports in adults consider that FNA is superior to thyroid ultrasonography (USG) and radionuclide scanning (RS). Only five studies have been published on FNA of childhood thyroid nodules. AIMS—To investigate the reliability of FNA in the evaluation and management of thyroid nodules, and compare the results of FNA, USG, and RS with regard to final histopathological diagnosis. METHODS—FNA was performed in 46 children with thyroid nodules after USG and RS examination. We investigated the sensitivity, specificity, accuracy, and positive and negative predictive values of USG, RS, and FNA in their management. RESULTS—Six patients who had malignant or suspicious cells on FNA examination underwent immediate surgery. The other 40 patients received medical treatment according to their hormonal status. Fifteen of these nodules either disappeared or decreased in number and/or size. Surgery was performed in 25 patients who did not respond to therapy. Statistical analysis revealed sensitivity, specificity, accuracy, and positive and negative predictive values respectively as follows: 60%, 59%, 59%, 15%, and 92% for USG; 30%, 42%, 39%, 12%, and 68% for SC; 100%, 95%, 95%, 67%, and 100% for FNAB. CONCLUSION—FNAB is as reliable in children as in adults for definitive diagnosis of thyroid nodules. Using this technique avoids unnecessary thyroid surgery in children.

AIMS—To evaluate the performance of guidelines for emergency triage and treatment (ETAT) of children presenting to hospitals in the developing world. Part of the study was concerned with the delivery of emergency treatment to the sickest group of patients, characterisation of their illness, and outcome. METHODS AND RESULTS—A total of 236 children were admitted during the study period, 27 of whom died. The three main causes of death were malaria or malaria related illness (n = 7), pneumonia (n = 6), and malnutrition (n = 11). Forty seven children were categorised as needing emergency treatment. Thirty one had no treatment, and eight died; 16 received one or more recommended treatments, of whom five died. The main limitations to delivery of immediate care were the lack of staff in the department and lack of rapidly available blood.

AIMS—To describe the clinical features of rheumatic fever and to assess the Jones criteria in a population and setting similar to that in many developing countries. METHODS—The charts of 555 cases of confirmed acute rheumatic fever in 367 patients (97% Aboriginal) and more than 200 possible rheumatic fever cases from the tropical "Top End" of Australia's Northern Territory were reviewed retrospectively. RESULTS—Most clinical features were similar to classic descriptions. However, monoarthritis occurred in 17% of confirmed non-chorea cases and 35% of unconfirmed cases, including up to 27 in whom the diagnosis was missed because monoarthritis is not a major manifestation. Only 71% and 25% of confirmed non-chorea cases would have had fever using cut off values of 38°C and 39°C, respectively. In 17% of confirmed non-chorea cases, anti-DNase B titres were raised but antistreptolysin O titres were normal. Although features of recurrences tended to correlate with initial episodes, there were numerous exceptions. CONCLUSIONS—Monoarthritis and low grade fever are important manifestations of rheumatic fever in this population. Streptococcal serology results may support a possible role for pyoderma in rheumatic fever pathogenesis. When recurrences of rheumatic fever are common, the absence of carditis at the first episode does not reliably predict the absence of carditis with recurrences.

Liquid paraffin or mineral oil is a transparent, colourless, odourless, or almost odourless, oily liquid composed of saturated hydrocarbons obtained from petroleum.1 Petroleum was used as a medicine at least 400 years before Christ.2 The earliest internal use of refined petroleum appears to date back to 1872, when Robert A. Chesebrough was granted a patent for the manufacture of “a new and useful product from petroleum”.2 The use of liquid paraffin gained popularity, after Sir W. Arbuthnot Lane, Chief Surgeon of Guy's Hospital in 1913, recommended its use as a treatment for intestinal stasis and chronic constipation.3 The popularity of liquid paraffin as a treatment for constipation and encopresis stems primarily from its tolerability and ease of titration. Although conversion of mineral oil to hydroxy fatty acids induces an osmotic effect,4 liquid paraffin appears to work primarily as a stool lubricant.5 Therefore, liquid paraffin is not associated with abdominal cramps, diarrhoea, flatulence, electrolyte disturbances, or the emergence of tolerance with long term usage, side effects commonly associated with osmotic or stimulant laxatives.6 These features make liquid paraffin particularly attractive for use in chronic constipation and encopresis of childhood, where large doses and prolonged administration commonly are necessary during the disimpaction and maintenance phases of treatment, respectively.6 However, although liquid paraffin is widely accepted and recommended as a fundamental component of regimens for the management of constipation in North America and Australia,6 7 it is little used in the United Kingdom.8 9 This trans-Atlantic dichotomy in liquid paraffin usage has been underscored by the American Academy of Pediatrics (AAP) endorsement of practice guidelines developed by the North American Society for Pediatric Gastroenterology and Nutrition (NASPGN) for the management of constipation in infants and children.6 NASPGN clearly identify liquid paraffin (mineral …

The median life expectancy for cystic fibrosis is now over 30 years, and it is projected that in newborn infants it will become more than 40 years. The identification of the cystic fibrosis gene and its product, cystic fibrosis transmembrane conductance regulator (CFTR), has widened the spectrum of the disease from the classical case of the infant with cystic fibrosis to the elderly childless man with unexplained bronchiectasis. There is increasing evidence of the advantages of newborn screening for cystic fibrosis and subsequent specialist care. Management concentrates on optimising nutritional status and preventing lung infection and inflammation.

AIMTo define practice in managing repeated invasive procedures in selected paediatric oncology centres in North America and Europe, especially the United Kingdom; to define and contrast concerns that shape policy making, and to contrast practice, particularly regarding procedures performed on conscious patients.METHODSPostal survey: 118 centres of the Pediatric Oncology Group and the United Kingdom Children's Cancer Study Group received questionnaires.RESULTS68 questionnaires (58%) were returned (52 from North America, 12 from Europe). For all procedures, North American centres tended to use less effective techniques than European, especially for bone marrow procedures. Many North American centres reported performing these on conscious patients on at least three quarters (25%) or half (30%) the occasions. In contrast, corresponding figures for the European centres were 6% and 0%.CONCLUSIONSMany bone marrow procedures are still carried out in the conscious patient despite the safety and effectiveness of modern anaesthetic and deep sedation techniques. There appears to be a greater reluctance to offer these to patients in North American centres than in European ones. This may reflect a misperception that the risks of adverse effects are high. Several non-pharmacological techniques are used, but they remain uncommon.

BACKGROUNDCerebral oedema is a major cause of morbidity and mortality in children with insulin dependent diabetes.AIMSTo determine the risk and outcome of cerebral oedema complicating diabetic ketoacidosis (DKA).METHODSAll cases of cerebral oedema in England, Scotland, and Wales were reported through the British Paediatric Surveillance Unit between October 1995 and September 1998. All episodes of DKA were reported by 225 paediatricians identified as involved in the care of children with diabetes through a separate reporting system between March 1996 and February 1998. Further information about presentation, management, and outcome was requested about the cases of cerebral oedema. The risk of cerebral oedema was investigated in relation to age, sex, seasonality, and whether diabetes was newly or previously diagnosed.RESULTSA total of 34 cases of cerebral oedema and 2940 episodes of DKA were identified. The calculated risk of developing cerebral oedema was 6.8 per 1000 episodes of DKA. This was higher in new (11.9 per 1000 episodes) as opposed to established (3.8 per 1000) diabetes. There was no sex or age difference. Cerebral oedema was associated with a significant mortality (24%) and morbidity (35% of survivors).CONCLUSIONSThis first large population based study of cerebral oedema complicating DKA has produced risk estimates which are more reliable and less susceptible to bias than those from previous studies. Our study indicates that cerebral oedema remains an important complication of DKA during childhood and is associated with significant morbidity and mortality. Little is known of the aetiology of cerebral oedema in this condition and we are currently undertaking a case control study to address this issue.

OBJECTIVETo investigate the use of 99mTc-HMPAO (hexamethyl propylene amine oxime) leucocyte scintigraphy as a non-invasive screening test for inflammatory bowel disease.PATIENTS10 children with suspected Crohn's disease, in whom routine investigation using barium contrast radiology, upper gastrointestinal endoscopy, colonoscopy, and mucosal biopsies had identified severe gastroduodenal and/or jejunal involvement.DESIGN99mTc-HMPAO leucocyte scintigraphic studies performed in each of these cases were assessed by a radiologist who was blinded to the disease distribution.RESULTSIn nine cases there was no scintigraphic evidence of inflammation in the proximal gastrointestinal tract. The 10th child had both gastroduodenal and jejunal involvement, but scintigraphy only revealed faint jejunal positivity.CONCLUSIONS99mTc-HMPAO leucocyte scintigraphy should not be depended upon as a screening test for Crohn's disease. False negative results are likely in cases with Crohn's disease confined to the proximal gastrointestinal tract.

We describe a 21 month old male infant who presented with failure to thrive associated with severe hypokalaemia and metabolic acidosis, together with hypomagnesaemia. Evaluation revealed marked renal and probable faecal potassium wasting, distal renal tubular acidosis, mild urinary magnesium wasting, and a normal gastric pH (gastric H+-K+-ATPase). Hypokalaemic forms of metabolic acidosis, such as diabetic ketoacidosis and proximal renal tubular acidosis were ruled out from the clinical picture. The hypokalaemia of distal renal tubular acidosis usually improves with alkali therapy, but this was not observed: despite correction of acidosis with 5 mmol/kg potassium citrate per day, an additional 5 mmol/kg potassium chloride was required to bring serum potassium to 3.5 mmol/l. At 3 years of age potassium was provided in the absence of potential alkali and acidosis ensued; serum bicarbonate fell to 10 mmol/l. Although a specific genetic analysis is not yet possible, the abnormalities are consistent with a novel form of distal renal tubular acidosis. The pathophysiology probably does not stem from defects in the vacuolar H+-ATPase but more likely from deficient activity of the colonic isoform of H+-K+-ATPase that is resident in the medullary collecting duct and mediates potassium absorption and proton secretion.

AIMTo investigate bone mineral status of children with cystic fibrosis (CF).METHODSIn 29 children with CF and 49 matched controls, bone mineral content (BMC), projected bone area (BA), and areal bone mineral density (BMD) of the whole body, total hip, and lumbar spine (L1–L4) were measured using dual energyxray absorptiometry. The BMC values at each site were adjusted for BA, height, and weight. At the lumbar spine, the bone mineral apparent density (BMAD) was calculated by dividing the BMC by the estimated volume, derived from BA. Vertebral (T12–L3) trabecular bone mineral density (vTBMD) was measured using quantitative computed tomography in children with CF. Calcaneal broadband ultrasound attenuation (BUA) was measured in CF patients and controls using quantitative ultrasound. The disease severity of CF children was evaluated by the Shwachman–Kulczycki (SK) score.RESULTSThe mean BUA, whole body and regional BA, adjusted BMC, and areal BMD of children with CF were not different from those of controls. The mean BMAD of the lumbar spine was reduced in CF patients compared with controls, whereas the mean vTBMD standard deviation scores were significantly higher in CF patients. The median SK score of the CF group was 81 (range 42–100), indicating that as a group our CF patient population had relatively mild disease.CONCLUSIONThe normal vertebral BMC, decreased BMAD, and higher vTBMD suggests that the vertebral cortical thickness or density might be reduced in CF subjects. The overall bone mineral status of CF children with relatively mild disease was not different from size matched controls.

BACKGROUNDCD40 ligand (CD40L) deficiency is a rare X linked immunodeficiency disorder leading to recurrent bacterial infection, with cryptosporidial enteritis and subsequent hepatic cirrhosis. Bone marrow transplantation offers the only cure.OBJECTIVETo analyse retrospectively the outcome of bone marrow transplantation for this condition in one centre.DESIGNA retrospective case note analysis was performed, identifying all patients with CD40L deficiency who had undergone bone marrow transplantation between May 1988 and December 2000. Details of pre-existing infection, pretransplantation immunological and infective data, transplant procedure (particularly donor type and HLA match), conditioning regimen, and marrow manipulation were analysed. Post-transplantation data including infective episodes, engraftment details, immune function, complications, and outcome were recorded.RESULTSEight boys (age 1–14 years, median 5.75) had transplants. Six received T cell depleted unrelated donor marrow. Four survive and have normal immune function. Six had previous Pneumocystis carinii pneumonia and three had histological liver damage. Survival was associated with younger age at transplantation and normal liver histology.CONCLUSIONSBone marrow transplantation can be curative in CD40L deficiency. Better outcome is associated with younger age at transplantation and normal liver histology.

Background—Growth hormone (GH) has been used to promote growth in both the short and long term in a number of dysmorphic syndromes, including Turner syndrome. As this condition shares many clinical features with Noonan syndrome, it would seem logical to treat the latter group with GH. Aims—To assess the short and long term response to GH therapy in patients with Noonan syndrome. Methods—Analysis of patients with Noonan syndrome in the Pharmacia & Upjohn International Growth Study (this postmarketing database contains data on the majority of patients currently treated with GH in the UK). A questionnaire was also sent to participating clinicians. Results—Data on 66 patients (54 males) were available for study.At the start of GH therapy children were short, compared with both normal and Noonan children. During the first year of GH therapy height velocity increased from a mean of 4.9 to 7.2 cm per year. For patients treated long term with GH, mean height SDS increased from ˛2.9 pretreatment to ˛2.6 after one year and ˛2.3 after five years. Of the 10 patients at near final height, only one had a height above the 3rd centile for normal adults and above the mean for untreated Noonan patients. The mean increment in final height was 3.1 cm (range ˛1.1 to 6.5 cm). Conclusions—GH therapy in patients with Noonan syndrome will improve height velocity in the short term. Longer-term therapy results in a waning of eVect;initial indications are that final height is not improved substantially in most patients. (Arch Dis Child 2001;84:440‐443)

As part of a population based regional review of all neonatal readmissions, the incidence of dehydration with hypernatraemia in exclusively breast fed infants was estimated. All readmissions to hospital in the first month of life during 1998 from a population of 32 015 live births were reviewed. Eight of 907 readmissions met the case definition, giving an incidence of at least 2.5 per 10 000 live births. Serum sodium at readmission varied from 150to 175 mmol/l. One infant had convulsions. The sole explanation for hypernatraemia was unsuccessful breast feeding in all cases. The eight cases are compared with the 65 cases published in the literature since 1979. Presentation, incidence, risk factors, pathophysiology, treatment, and prevention are discussed.

AIMTo study the effect of folate treatment on hyperhomocysteinaemia and the effect of 5,10-methylenetetrahydrofolate reductase (MTHFR) gene polymorphism on total homocysteine and folate concentrations after renal transplantation.METHODSA total of 30 transplanted children and adolescents were investigated for total homocysteine and folate serum concentrations before and after folate treatment, as well as for the presence of the MTHFR C677T polymorphism.RESULTSThe allele frequency of C677T polymorphism in the MTHFR gene in the study population (0.33) was not different to that in controls (0.38). Before folate treatment the homocysteine concentration was raised in all groups; following folate supplementation it was significantly decreased in the CC and CT groups, but not in the TT group. In patients with CC genotype, serum homocysteine correlated with serum creatinine and cholesterol, and time since transplantation before treatment.CONCLUSIONFolate supplementation appears to be an effective strategy to normalise total homocysteine concentration in renal transplanted children and adolescents.

AIMS—To present our experience of severe upper airway obstruction caused by ulcerative laryngitis in children. METHODS—Retrospective case note review of 263 children with severe upper airway obstruction and a clinical diagnosis of croup admitted to a paediatric intensive care unit (PICU) over a five year period. RESULTS—A total of 148 children (56%) underwent microlaryngoscopy (Storz 3.0 rigid telescope). Laryngeal ulceration with oedema was documented in 15 of these children (10%), median age 14 months (range 10-36) and median weight 10 kg (range 6-12). Twenty seven of the children who underwent microlaryngoscopy (18%) also had ulcerative gingivostomatitis consistent with herpes simplex virus infection. Ulcerative laryngitis was documented in nine of 27(33%) children with, and in six of 121 (5%) children without, coexistent ulcerative gingivostomatitis. One of the 15 children did not require airway intervention. Nine children required nasotracheal intubation for a median of 4 days (range 3-11) and median PICU stay of 6 days (range 4-14). Five children required tracheostomy ab initio, with a median PICU stay of 30 days (range 20-36), and duration of tracheostomy in situ for a median of 19 days (range 15-253). All 15 children survived. CONCLUSION—Ulcerative laryngitis is more common in our patient population than the few reports suggest. Early diagnostic microlaryngoscopy is recommended in children with severe croup who follow an atypical course.

AIM To evaluate the long term outcome after paediatric inferior vena cava (IVC) thrombosis. METHODS A combined retrospective and prospective study on infants and children with IVC thrombosis treated at Aachen and Maastricht University Hospitals between 1980 and 1999. RESULTS Forty patients were enrolled, including four with preceding cardiac catheterisation, 18 with central venous saphenous lines, and an additional eight with umbilical venous catheters. Six patients died within three months of diagnosis; one patient was lost to follow up. Twelve of the remaining 33 patients had suffered from limited IVC thrombosis; during follow up (for up to nine years) none showed persisting caval obstruction (successful thrombolysis, n = 2; spontaneous recanalisation, n = 10). The remaining 21 patients presented with extensive IVC thrombosis. During follow up (for up to 18 years) complete restitution was found in only four cases (one thrombolysis, two surgery, one spontaneous recanalisation). Persisting iliac and/or caval venous obstruction occurred in 17 patients, including six with thrombolysis. Varicose veins were found in 12, and post-thrombotic syndrome in seven of these cases. According to Kaplan–Meier analysis, 30% of patients with persisting venous disease will develop post-thrombotic syndrome within 10 years of the thrombotic event. CONCLUSIONS Infants and children with extensive IVC thrombosis are at high risk for persisting venous disease and serious long term complications. Prospective trials are urgently needed to establish effective treatment strategies and to improve long term prognosis. Central venous catheters, contributing to IVC thrombosis in the majority of cases reported here, should be inserted only if essential.

AIMS To examine a number of simple clinical features and investigations in children with a non-blanching rash to see which predict meningococcal infection. METHODS A total of 233 infants and children up to 15 years of age presenting with a non-blanching rash were studied over a period of 12 months. Clinical features and laboratory investigations were recorded at presentation. The ability of each to predict meningococcal infection was examined. RESULTS Eleven per cent had proven meningococcal infection. Children with meningococcal infection were more likely to be ill, pyrexial (>38.5°C), have purpura, and a capillary refill time of more than two seconds than non-meningococcal children. Five children with meningococcal disease had an axillary temperature below 37.5°C. No child with a rash confined to the distribution of the superior vena cava had meningococcal infection. Investigations were less helpful, although children with meningococcal infection were more likely to have an abnormal neutrophil count and a prolonged international normalised ratio. No child with a C reactive protein of less than 6 mg/l had meningococcal infection. CONCLUSIONS Most children with meningococcal infection are ill, have a purpuric rash, a fever, and delayed capillary refill. They should be admitted to hospital and treated without delay. Children with a non-blanching rash confined to the distribution of the superior vena cava are very unlikely to have meningococcal infection. Measurement of C reactive protein may be helpful—no child with a normal value had meningococcal infection. Lack of fever at the time of assessment does not exclude meningococcal disease.

Chyloperitoneum is a rare and challenging complication of abdominal surgery. We report a case of iatrogenic chyloperitoneum. Infusion of octreotide, a somatostatin analogue, together with total parenteral nutrition followed by medium chain triglyceride diet resulted in rapid resolution of chyloperitoneum. We believe this to be the first report of successful use of octreotide in iatrogenic chyloperitoneum in a child.

Chest wall hamartoma of infancy is a rare lesion, usually presenting in the first year of life. Recent literature has recommended conservative management of asymptomatic children, yet most continue to undergo surgical resection irrespective of their symptom status. We report a case of spontaneous regression of a chest wall hamartoma of infancy, supporting recommendations for conservative management in asymptomatic children.

BACKGROUND—Routine hospital statistics for England appear to overestimate use of children's wards and include numbers of well newborn babies staying with their mothers after delivery ("well babies"). AIM—To review trends in use of children's wards excluding data on newborn babies. METHODS—We reviewed routine, published, and age stratified data requested from the Department of Health to identify separately "well babies" and babies receiving neonatal specialist care from admissions (surgical and paediatric) to children's wards. RESULTS—Routine reports for paediatric activity contain large numbers of "well babies", (almost half the total) as well as babies receiving specialist neonatal care. After excluding these, paediatric admissions represent 9.9% of the child population aged under 5years each year (an additional 2.5% are admitted for surgical care). Between 1989 and 1997 paediatric admissions rose by 19% and surgical admissions fell by 25% with a plateau reached in overall child admissions. There are now fewer beds in which children stay for a shorter time and there is more day case surgery. Neonatal specialist care work has risen despite a fall in births. CONCLUSION—Categories should be established for reporting paediatric episodes on children's wards separately from those on neonatal units, with better identification of "well babies". When monitoring use of children's inpatient facilities or planning new units, care must be taken to separate paediatric data on neonatal units from work on children's wards. Children's surgical episodes should also be taken into account.

Hyponatraemia is a common finding in patients with acute cerebral insults. The main differential diagnosis is between syndrome of inappropriate ADH secretion and cerebral salt wasting. Our aim is to review the topic of hyponatraemia in patients with acute cerebral insults and suggest a clinical approach to diagnosis and management.

A female infant presented with facial palsy and was found to be severely hypertensive. Plasma renin activity was raised and an angiogram showed middle aortic syndrome. This condition is of unknown aetiology, but positive antineutrophil cytoplasmic antibodies may indicate a vasculitis which heals by intimal fibrosis, causing the observed findings.

Aim—To assess guidelines for the emergency triage, assessment, and treatment (ETAT) of sick children presenting to hospitals in the developing world. This study pretested the guidelines in Malawi, assessing their performance when used by nurses compared to doctors trained in advanced paediatric life support (APLS). Methods—Triage was performed simultaneously by a nurse and assessing doctor on 2281 children presenting to the under 5s clinic. Each patient was allocated one of three priorities, according to the ETAT guidelines. Any variation between nurse and assessor was recorded on the assessment forms. Results—Nurses identified 92 children requiring emergency treatment and 661 with signs indicating a need for urgent medical assessment. One hundred and forty two (6.2%) had diVerent priorities allocated by the APLS trained doctor, but these children did not tend to need subsequent admission. Eighty five per cent of admissions were prioritised to an emergency or urgent category. Conclusion—Although there are no gold standards for comparison the ETAT guidelines appear to reliably select out the majority of patients requiring admission. (Arch Dis Child 2001;85:208‐213)

BACKGROUNDIn recent years photopheresis, an extracorporeal form of photochemotherapy using psoralen and ultraviolet A irradiation of leucocytes, has been claimed to be an effective form of immunomodulation.AIMTo evaluate its effect in type 1 diabetes we performed a double blind, controlled study using placebo tablets and sham pheresis in the control group.METHODSA total of 49 children, aged 10–18 years of age at diagnosis of type 1 diabetes were included; 40 fulfilled the study and were followed for three years (19 received active treatment with photopheresis and 21 placebo treatment).RESULTSThe actively treated children secreted significantly more C peptide in urine during follow up than control children. C peptide values in serum showed corresponding differences between the two groups. The insulin dose/kg body weight needed to achieve satisfactory HbA1c values was always lower in the photopheresis group; there was no difference between the groups regarding HbA1c values during follow up. The treatment was well accepted except for nausea (n = 3) and urticaria (n = 1) in the actively treated group. There were no differences regarding weight or height, or episodes of infection between the two groups during follow up.CONCLUSIONPhotopheresis does have an effect in addition to its possible placebo effect, shown as a weak but significant effect on the disease process at the onset of type 1 diabetes, an effect still noted after three years of follow up.

BACKGROUNDThe role of inhaled corticosteroids for the treatment of wheeze in infancy remains unclear.AIMTo investigate the effect of inhaled fluticasone on symptoms in a group of wheezy infants who had a high risk of progressing to childhood asthma.METHODSA total of 52 infants, under 1 year of age, with a history of wheeze or cough and a history (personal or first degree relative) of atopy were prescribed either 150 μg fluticasone twice daily (group F) or placebo (group P), via metered dose inhaler, for 12 weeks following a two week run in period. Symptoms were scored in a parent held diary and the mean daily symptom score (MDS) and symptom free days (SFD) calculated for each two week period.RESULTSThirty seven infants completed the study. Both MDS and SFD improved significantly between the run in and final two week period in group F, but not group P, with a mean difference in change (95% CI) between groups of 1.12 (0.05 to 2.18) for MDS and median difference of 3.0 (0.002 to 8.0) for SFD.CONCLUSIONImprovement of clinical symptoms in response to fluticasone can be shown in this high risk group of infants. In the absence of effective alternatives inhaled corticosteroids should be considered in this patient group.

AIMTo evaluate the reliability of dipstick measurements of urine specific gravity (U-SG).METHODSFresh urine specimens were tested for urine pH and osmolality (U-pH, U-Osm) by a pH meter and an osmometer, and for U-SG by three different methods (refractometry, automatic readout of a dipstick (Clinitek-50), and (visual) change of colour of the dipstick).RESULTSThe correlations between the visual U-SG dipstick measurements and U-SG determined by a refractometer and the comparison of Clinitek®-50 dipstick U-SG measurements with U-Osm were less than optimal, showing very wide scatter of values. Only the U-SG refractometer values and U-Osm had a good linear correlation. The tested dipstick was unreliable for the bedside determination of U-SG, even after correction for U-pH, as recommended by the manufacturer.CONCLUSIONSAmong the bedside determinations, only refractometry gives reliable U-SG results. Dipstick U-SG measurements should be abandoned.

OBJECTIVETo develop an evidence and consensus based guideline for the management of the child who presents to hospital with diarrhoea (with or without vomiting), a common problem representing 16% of all paediatric medical attenders at an accident and emergency department. Clinical assessment, investigations (biochemistry and stool culture in particular), admission, and treatment are addressed. The guideline aims to aid junior doctors in recognising children who need admission for observation and treatment and those who may safely go home.EVIDENCEA systematic review of the literature was performed. Selected articles were appraised, graded, and synthesised qualitatively. Statements on recommendation were generated.CONSENSUSAn anonymous, postal Delphi consensus process was used. A panel of 39 selected medical and nursing staff were asked to grade their agreement with the generated statements. They were sent the papers, appraisals, and literature review. On the second and third rounds they were asked to re-grade their agreement in the light of other panellists' responses. Consensus was predefined as 83% of panellists agreeing with the statement.RECOMMENDATIONSClinical signs useful in assessment of level of dehydration were agreed. Admission to a paediatric facility is advised for children who show signs of dehydration. For those with mild to moderate dehydration, estimated deficit is replaced over four hours with oral rehydration solution (glucose based, 200–250 mOsm/l) given “little and often”. A nasogastric tube should be used if fluid is refused and normal feeds started following rehydration. Children at high risk of dehydration should be observed to ensure at least maintenance fluid is tolerated. Management of more severe dehydration is detailed. Antidiarrhoeal medication is not indicated.VALIDATIONThe guideline has been successfully implemented and evaluated in a paediatric accident and emergency department.

AIMSTo establish criteria for early distinction between meningococcal disease and other conditions with similar clinical features, and to identify other causes for haemorrhagic rashes accompanied by fever.METHODSIn a prospective study, 264 infants and children hospitalised with fever and skin haemorrhages were studied.RESULTSWe identified an aetiological agent in 28%: 15% had meningococcal disease, 2% another invasive bacterial infection, 7% enterovirus infection, and 4% adenovirus infection. Five clinical variables distinguished between meningococcal disease and other conditions on admission: (1) skin haemorrhages of characteristic appearance; (2) universal distribution of skin haemorrhages; (3) maximum diameter of one or more skin haemorrhages greater than 2 mm; (4) poor general condition (using a standardised observation scheme); and (5) nuchal rigidity. If any two or more of these clinical variables were present, the probability of identifying a patient with meningococcal disease was 97% and the false positive rate was only 12%. This diagnostic algorithm did not identify children in whom septicaemia was caused by other bacterial species.

BACKGROUNDEarly and accurate diagnosis of Crigler–Najjar syndrome, which causes prolonged unconjugated hyperbilirubinaemia in infancy, is important, as orthotopic liver transplantation is the definitive treatment.AIMTo determine whether bilirubin pigment analysis of bile in infants with prolonged unconjugated hyperbilirubinaemia provides useful diagnostic information in the first 3 months of life.METHODSRetrospective review of patients with prolonged unconjugated hyperbilirubinaemia referred to the liver unit, Birmingham Children's Hospital, for the diagnosis of Crigler–Najjar syndrome. Bile bilirubin pigment composition was determined by high performance liquid chromatography. Initial diagnoses were made based on the result of bile bilirubin pigment composition. Final diagnoses were made after reviewing the clinical course, response to phenobarbitone, repeat bile bilirubin pigment composition analysis, and genetic studies.RESULTSBetween 1992 and 1999, nine infants aged less than 3 months of age with prolonged hyperbilirubinaemia underwent bile bilirubin pigment analyses. Based on these, two children were diagnosed with Crigler–Najjar syndrome (CNS) type 1, six with CNS type 2, and one with Gilbert's syndrome. Five children whose initial diagnosis was CNS type 2 had resolution of jaundice and normalisation of serum bilirubin after discontinuing phenobarbitone, and these cases were thought to be normal or to have Gilbert's syndrome. One of the initial cases of CNS type 1 responded to phenobarbitone with an 80% reduction in serum bilirubin consistent with CNS type 2. In all, the diagnoses of six cases needed to be reviewed.CONCLUSIONSEarly bile pigment analysis, performed during the first 3 months of life, often shows high levels of unconjugated bilirubin or bilirubin monoconjugates, leading to the incorrect diagnosis of both type 1 and type 2 Crigler–Najjar syndrome.

BACKGROUNDLittle is known of the optimal dose and administration schedule of hydrocortisone in critically ill patients with congenital adrenal hyperplasia (CAH) caused by 21-hydroxylase deficiency.AIMTo determine plasma cortisol concentrations after intravenous administration of hydrocortisone in children with CAH and to relate these to plasma cortisol concentrations achieved by endogenous secretion in the stress of critical illness in previously healthy children.METHODSPlasma cortisol concentrations were measured in 20 patients with classical CAH (median age 11.2 years, range 6.1–16.4) following intravenous administration of hydrocortisone 15 mg/m2; and in 60 critically ill mechanically ventilated children (median age 2.5 years, range 0.25–16.3) on admission to the paediatric intensive care unit and for 24 hours thereafter.RESULTSIn the CAH patients, plasma cortisol reached a mean peak of 1648.3 nmol/l (SD 511.9) within 10 minutes of the intravenous bolus, and fell rapidly thereafter; levels remained greater than 450 nmol/l for 2.5 hours only. In critically ill children, mean plasma cortisol on admission to the intensive care unit was 727 nmol/l (SD 426.1). Cortisol concentrations remained raised during the first 24 hours.CONCLUSIONSCritically ill patients with classical CAH may be best managed with a single intravenous hydrocortisone bolus followed by a constant rate infusion of hydrocortisone.

Intracavernous injections of etilefrine were effective in seven children with acute sickle cell priapism, and stuttering priapism resolved in five children after one to seven months of oral etilefrine. Compared with our previous reports in adults, etilefrine appears to be more effective in childhood.

OBJECTIVETo investigate the relation between total serum IgE at 0.5–3 and 3–6 years, and the risk of allergic sensitisation and persistent wheezing up to 8 years of age.METHODSProspective follow up study of 45 infants with highly recurrent wheezing, no allergic symptoms, and negative skin tests.RESULTSIn the last follow up year, 15 children still suffered from wheezing. Five wheeze-free and four episodically wheezing children had become sensitised. No association was found between early (0.5–3 years) IgE z scores and the recurrence of wheezing during follow up, or atopic sensitisation. IgE z scores at 3–6 years were significantly higher in children with positive skin tests (p = 0.013), but were still not associated with recurrence of wheezing.CONCLUSIONSIn subjects with frequent early wheezing and no signs of atopy, early total serum IgE measurements are not predictive of outcome.

Over the 10 year period 1987–1996, 328 children with type 1 diabetes mellitus presented in the city of Birmingham, England, of whom 27% had diabetic ketoacidosis. Asian children under the age of 5 had an eightfold increased risk of presenting in diabetic ketoacidosis compared with non-Asian children of the same age.

In Costa Rica there is little information about asthma admissions. In this report the monthly asthma admissions and weather data for a seven year period were reviewed. The hospital asthma admissions showed notable seasonal variation associated with variations in the rainfall and the relative humidity.

AIMSTo evaluate the efficacy and safety of nitrous oxide for children undergoing painful procedures.METHODSNinety children requiring repeated painful procedures (lumbar puncture, bone marrow aspirate, venous cannulation, or dressing changes) were given nitrous oxide at a variable concentration of 50–70%. Procedure related distress was evaluated using the Observational Scale of Behavioral Distress–Revised (OSBD-R). OSBD-R scores were obtained for each of the following phases of the procedure: phase 1a, waiting period; phase lb, during induction with nitrous oxide; phase 2, during positioning and cleaning of the skin; phase 3, during the painful procedure; and phase 4, immediately following the procedure and withdrawal of nitrous oxide. Side effects were monitored and recorded by a second observer.RESULTSOSBD scores reached a maximum during the induction phase with lower scores during subsequent phases. Children over the age of 6 showed a lower level of distress during nitrous oxide administration and the painful procedure. Eighty six per cent of patients had no side effects. The incidence of vomiting, excitement, and dysphoria was 7.8%, 4.4%, and 2% respectively. Eight patients developed oxygen desaturation (Sao2< 95%), but none developed hypoxia, airway obstruction, or aspiration. Ninety three per cent of patients fulfilled the criteria for conscious sedation, and 65% had no recollection of the procedure. Mean recovery time was three minutes.CONCLUSIONSInhalation of nitrous oxide is effective in alleviating distress during painful procedures, with minimal side effects and short recovery time.

AIMTo describe 21 cases of symptomatic rickets in adolescents.METHODSThe setting was a primary and secondary care hospital in Saudi Arabia providing medical care to Saudi Arab company employees and their families. Cases of symptomatic rickets diagnosed between January 1996 and December 1997 in adolescents aged 10 to 15 years were assessed with respect to clinical presentation, biochemical and radiological evaluation, dietary assessment, and estimation of sun exposure.RESULTSSymptomatic rickets developed in 21 adolescents (20 females), with a prevalence rate of 68 per 100 000 children years. Presentation included carpopedal spasms (n = 12), diffuse limb pains (n = 6), lower limbs deformities (n = 2), and generalised weakness (n = 1). Biochemical findings included hypocalcaemia (n = 19), hypophosphoraemia (n = 9), raised serum alkaline phosphatase (n = 21) and parathormone (n = 7), and reduced 25-hydroxyvitamin D concentrations (n = 7). Radiological studies were suggestive of rickets in only eight children. All children had an inadequate dietary calcium and vitamin D intake. All but one had less than 60 minutes sun exposure per day.CONCLUSIONEven in sunny climates, adolescents, especially females, can be at risk of rickets. Hypocalcaemic tetany and limb pains were the most common presenting symptoms. Radiological evidence was not present in every case.

Three infants with subphrenic abscess, pyonephrosis, and obstructive ureterocoele respectively had grossly increased concentrations of plasma ammonia. This was considered to be a result of infections with urea splitting organisms. All died in spite of intensive care support, including specific measures to reduce plasma ammonia.

AIMSTo assess the annual risk of influenza infection in children with cancer and the immunogenicity of a trivalent split virus influenza vaccine in these children.METHODSEighty four children with cancer were tested for susceptibility to the circulating strains of influenza virus in autumn 1995 and 1996. Non-immunised children were reassessed the following spring for serological evidence of natural infection. Forty two patients received two doses of influenza vaccine. These children were receiving continuing chemotherapy for acute lymphoblastic leukaemia or were within six months of completing chemotherapy.RESULTSAmong the 84 children tested for influenza virus susceptibility only 8% of patients were fully protected (antibody titres ⩾ 40) against all three of the prevalent influenza virus strains; 33% were susceptible to all three viruses. Evidence of acquired natural infection was seen in 30% of unimmunised patients. Among immunised susceptible patients, 66% made some protective response to the vaccine and 55% showed protective antibody titres to all three viral strains following vaccination. Older age was associated with increased response to the H1N1 and H3N2 vaccine components, but total white cell count or neutrophil count at immunisation, type of cancer, or length of time on treatment for acute lymphoblastic leukaemia did not affect response.CONCLUSIONSMost children with cancer studied were at risk of influenza infection. A significant response to immunisation was seen, supporting annual influenza vaccination for children being treated for cancer.

AIMS—To investigate whether paediatricians have improved their resuscitation knowledge since 1992, and whether those who have attended a paediatric resuscitation course have greater knowledge than those who have not. METHODS—Telephone survey of 94 resident paediatricians admitting emergency cases. Questions on clinical scenarios were asked and adherence to internationally agreed guidelines in answering was determined. RESULTS—There were significantly more correct answers to 9/10 questions in 1999 compared to 1992. The 1999 doctors who had attended a course scored significantly better in 3/10 questions and achieved a higher total score (5.43 versus 4.55). CONCLUSIONS—Knowledge has improved since 1992; this has been over the period in which paediatric resuscitation courses were introduced. In 1999 those who had been on a course were more knowledgeable than those who had not.

WE DESCRIBE FOUR PATIENTS WITH NIEMANN—Pick disease type C (NPC), in whom the presentation was isolated splenic enlargement; this remained the only abnormality for a number of years. Diagnosis can be suggested by either finding abnormal storage material in a tissue biopsy specimen or by showing a modest elevation in plasma chitotriosidase activity. In patients with suggestive abnormalities, filipin staining of a skin fibroblast sample should confirm the abnormality in cholesterol trafficking. Formal esterification studies and mutation analysis should also be performed, especially if prenatal testing is to be performed in subsequent pregnancies. If the diagnosis is not considered and established, the family are at risk of having further affected children. Investigation of patients with isolated splenomegaly is not complete until NPC has been excluded.

AIMS—To assess the impact of treatment for embryonal rhabdomyosarcoma on spinal growth and limb length and examine the response of these parameters to growth hormone (GH) treatment. METHODS—We conducted a retrospective case note review of 17 survivors of head and neck rhabdomyosarcoma followed up at a single institution. All children had been treated with chemotherapy and local radiotherapy. Growth velocity, height, sitting height, and subischial limb length SDS scores were analysed. RESULTS—Growth failure secondary to isolated GH deficiency (GHD) developed in 7/17 patients. GHD occurred at a median (range) of 3.4(1.3-9.9) years after radiotherapy tumour doses of 46 (40-50) Gy. Growth velocity, height, and subischial limb length SDS were significantly reduced in the GHD group and improved with GH therapy. CONCLUSIONS—GH treatment resulted in a significant improvement in sitting height SDS. We discuss the unexpected improvement in spinal growth in survivors with GHD.

AIM To investigate the safety of bronchoscopy and endobronchial biopsy in children with difficult asthma, and discuss the ethical issues associated with the procedure. METHODS A three year prospective observational study was performed in two tertiary paediatric respiratory centres specialising in the management of children with difficult asthma. A total of 48 children with difficult asthma and 35 non-asthmatic children were studied. RESULTS Flexible bronchoscopy was performed under general anaesthesia in 38 children with difficult asthma, and rigid bronchoscopy was performed in 10, following a two week course of prednisolone. Endobronchial biopsy was performed in 47 patients. Perioperative complications occurred in one asthmatic undergoing flexible bronchoscopy (desaturation) and in two undergoing rigid bronchoscopy (desaturation in one, and bronchospasm and desaturation in one). There were no cases of significant bleeding or pneumothorax among the asthmatics. Flexible bronchoscopy was performed in 35 non-asthmatic patients with a variety of clinical indications. The total number of perioperative complications was greater in the non-asthmatics undergoing flexible bronchoscopy than in the asthmatics (17 complications in 35 children versus one in 38). Fever requiring hospital admission was documented in two asthmatics following bronchoscopy. Four asthmatics reported an increase in symptoms in the week following bronchoscopy. CONCLUSIONS Bronchoscopy and endobronchial biopsy under general anaesthesia can be performed safely in children with difficult asthma, when the bronchoscopist and anaesthetist are suitably trained. The procedure is acceptable to the families involved.

AIMS—To compare two strategies for the eradication of Helicobacter pylori infection. METHODS—Groups 1 and 2 each consisted of 75 consecutive patients. Patients in group 1 were treated with two antibiotics based on antibiotic susceptibility testing; those in group 2 received amoxycillin and clarithromycin for eight days, together with either ranitidine or omeprazole. Eradication rate was assessed in both groups six months after treatment. RESULTS—In group 1, H pylori grew in culture in 63/75 cases. Susceptibility testing showed that 35/63 isolates were resistant to metronidazole, 10/63 to clarithromycin, 2/63 to ampicillin, 1/63 to tetracycline, and 5/63 to both clarithromycin and metronidazole. In group 1the infection was eradicated in 96% of the initial 75 subjects, and in 98% of the subjects treated according to the antibiotic assay (62/63). As two patients were lost at follow up the overall eradication rate was 99%. In group 2, eradication was achieved in 61/75 subjects (81%). This was significantly lower than the percentage of eradication observed in group 1 (81% versus 99%). CONCLUSIONS—Antibiotic susceptibility tests are useful in childhood as a very high percentage of subjects are cured. This approach is costly, but selective antibiotic treatment contributes to limit further development of antibiotic resistance, and money is saved in terms of reinvestigation and further repeated treatments.

Nebulised colistin is regularly used as antipseudomonal therapy in children with cystic fibrosis. We assessed bronchoconstriction in response to nebulised colistin in 58 children. Nebulised colistin significantly reduced FEV(1), MEF(25%), and SaO(2) for 15 minutes. In 20 children the reduction was greater than 10% from baseline FEV(1), and was still at that level in five at 30 minutes. Subjective assessment, baseline FEV(1), and serum IgE were unable to identify susceptible children. It is recommended that children receiving colistin should be carefully assessed for bronchoconstriction.

In a case control study of adverse drug reactions in children, the odds ratio of developing a serious mucocutaneous event among users of niflumic acid, adjusted for concomitant use of all other drugs, was 4.9 (95% CI 1.9 to 12.8). Given the availability of safer analgesics and antipyretics, there is no indication, in our opinion, that requires the prescription of substances which bear an increased risk.

AIMS—To determine the clinical course of childhood abdominal migraine, seven to 10 years after the diagnosis. METHODS—A total of 54 children with abdominal migraine were studied; 35 were identified from a population survey carried out on Aberdeen schoolchildren between 1991 and 1993, and 19 from outpatient records of children in the same age group who had attended the Royal Aberdeen Children's Hospital. Controls were 54 children who did not have abdominal pain in childhood, matched for age and sex, obtained from either the population survey or the patient administration system. Main outcome measures were presence or resolution of abdominal migraine and past or present history of headache fulfilling the International Headache Society (IHS) criteria for the diagnosis of migraine. RESULTS—Abdominal migraine had resolved in 31 cases (61%). Seventy per cent of cases with abdominal migraine were either current (52%) or previous (18%) sufferers from headaches that fulfilled the IHS criteria for migraine, compared to 20% of the controls. CONCLUSIONS—These results support the concept of abdominal migraine as a migraine prodrome, and suggest that our diagnostic criteria for the condition are robust.

BACKGROUNDThe hyperimmunoglobulinaemia D and periodic fever syndrome is a hereditary periodic fever, caused by deficiency of the enzyme mevalonate kinase. It is unclear how this defect leads to recurrent fever episodes.AIMTo assess the involvement of cysteinyl leukotrienes in the pathogenesis of fever attacks as reflected by urinary leukotriene E4(LTE4) excretion.METHODSUrinary LTE4was measured in seven patients while febrile and afebrile.RESULTSLTE4was raised during fever in all subjects (46–199 nmol/mol creatinine, mean 92; normal 4was normal between attacks, as well as in normal children with fever as a result of miscellaneous causes.CONCLUSIONOur results suggest that cysteinyl leukotrienes play a role in the pathophysiology of this disorder. As no effective treatment is yet available, leukotriene receptor antagonists might offer a new therapeutic approach for patients with the hyperimmunoglobulinaemia D and periodic fever syndrome.

Cholelithiasis is considered uncommon in infancy, childhood, and adolescence. We performed a prospective, controlled study showing that children with Down's syndrome have a significantly higher prevalence of cholelithiasis (4.7%) compared with controls (0.2%). Clinicians should be aware of the risk of gallstones in children with Down's syndrome.