A case of atypical Kawasaki disease with giant coronary artery aneurysm containing thrombus.

INTRODUCTION: Kawasaki disease (KD) is an acute febrile, systemic vasculitic syndrome of unknown etiology, occurring primarily in children younger than 5 years of age. Administration of IVIG within the first 10 days after onset of fever in combination with high dose aspirin reduces the risk of coronary artery damage in KD. Though rare, giant aneurysms of the coronary arteries may develop in untreated cases and prove extremely challenging to manage. CASE PRESENTATION: A 9-month-old Caucasian boy presented to our paediatric emergency department with a 4-week history of intermittent pyrexia and irritability. Typical mucocutaneous signs of Kawasaki Disease were absent upon presentation. A trans-thoracic echocardiogram identified a giant aneurysm of the left anterior descending artery with thrombus formation in-situ and the child was managed with intravenous immunoglobulin, steroids, high dose aspirin therapy and later warfarinisation. DISCUSSION: Cardiovascular sequelae of Kawasaki disease include giant coronary artery aneurysms with thrombosis. Enlargement of a coronary aneurysm after the acute phase of Kawasaki disease is uncommon and the outcome of interventional approaches poorly studied.

Accuracy of frozen section diagnosis at surgery in pre- malignant and malignant lesions of the endometrium.

OBJECTIVE: The purpose of this study was to correlate the histological diagnosis made during intraoperative frozen section examination of hysterectomies with atypical hyperplasia or carcinoma, with the definitive paraffin section histology. STUDY DESIGN: Frozen section pathology results of patients with a preoperative biopsy showing atypical hyperplasia or endometrial carcinoma (87 patients) were compared retrospectively with paraffin section pathology findings. Those patients with curettage specimens showing atypical hyperplasia or curettings suspicious of endometrioid carcinoma had intraoperative frozen section to determine whether an invasive lesion was present and whether they required pelvic lymphadenectomy. The purpose of frozen section assessment in those patients who had a preoperative curettage specimen showing endometrial carcinoma was to identify poor prognostic pathological factors related to histological subtype, grade, depth of myometrial invasion and cervical involvement. RESULTS: The correlation between frozen sections and paraffin histology in patients with endometrial carcinoma was 98.6% (69/70) for histological sub-type and 84.3% (59/70) for grade of differentiation. Depth of myometrial invasion was accurately diagnosed in 94.3% (66/70) while cervical involvement was accurately assessed in 86.7% (52/60). Of the 37 patients with atypical hyperplasia or suspicious curettings on preoperative curettage who had intraoperative frozen section, 23 patients had invasive malignancy, which was confirmed in subsequent paraffin sections. Of the remaining 14 patients with a non-malignant frozen section diagnosis, 11 were confirmed with paraffin sections while three had a small well differentiated invasive lesion, two were FIGO Stage 1a and one had microscopic invasion into the myometrium. CONCLUSION: Intraoperative frozen section is a useful procedure to identify poor prognostic pathological factors as well as to diagnose endometrial cancer in patients undergoing hysterectomy for a preoperative biopsy diagnosis of atypical hyperplasia.

Quality of life of 6-year-old survivors from a regional neonatal unit.

OBJECTIVE: Quality of life (QOL) of children who required treatment in a national neonatal intensive care unit (NICU) during the first week of life was determined at 6 years of age. METHOD: QOL was assessed using a standardized questionnaire employing a multi-attribute scoring system including the functions: hearing, vision, speech, mobility, emotion, learning, self-care and pain. After excluding those with congenital neurodevelopmental disorders, questionnaire returns were analyzed from 177 children treated in the NICU in 1990 and a comparative age-matched group of 230 children who did not require neonatal care. Of these, returns were obtained from 143 (81%) cases and 171 (74%) of the non-treated group. RESULTS: There was no difference in overall ability between the two groups, with 95 (66%) of cases and 126 (74%) of the comparison group reporting normal scores in all functions. Children treated in the NICU had decreased scores in individual functions including speech (p = 0.04), mobility (p = 0.009) and self-care (p = 0.006). For the study population, males had lower function in speech (p = 0.04) and learning (p = 0.001), with significantly worse function overall (p = 0.02) when compared with female cases. When compared with same-gender children who did not require NICU care, overall function was also significantly worse for male but not female cases (p = 0.0002), and this was largely contributed to by impairment in speech (p = 0.03), mobility (p = 0.04), learning abilities (p = 0.02) and self-care (p = 0.03). Eleven (7.7%) cases compared with just two (1.2%) children who were not treated in the NICU required assistance at school (p = 0.009). No difference was observed when QOL was assessed according to gestational age and birth weight. CONCLUSION: Using a simple scoring system this study has shown that, for survivors who required early neonatal intensive care, the QOL at 6 years compared favorably with that of children not treated in the NICU, especially for girls.

How reliable is axillary temperature measurement?

AIM: To assess whether axillary temperature measurements reliably reflect oral/rectal temperature measurements. METHODS: This observational study compared paired axillary-rectal and axillary-oral temperatures in a general paediatric ward with the participation of 225 children aged < or = 4 y and 112 children aged between 4 and 14 y. RESULTS: Changes in oral/rectal and axillary temperatures correlated significantly (p < 0.0001). However, axillary temperature measurements were significantly lower than both oral (mean -0.56 degrees C, SD 0.76 degrees C) and rectal measurements (0.38 degrees C; SD 0.76 degrees C). Ninety-five percent of axillary measurements fell within a 2.5-3 degrees C range around respective paired oral/rectal measurements. The mean difference increased with increasing temperature, and was 0.4 degrees C at low body temperatures, and over 1 degree C with a fever of 39 degrees C. Neither seasonal fluctuations nor the amount of clothing worn influenced this difference. CONCLUSION: Axillary temperatures in young children do not reliably reflect oral/rectal temperatures and should therefore be interpreted with caution.

Ethical Issues in Paediatric Practice - Part II: Issues relating to disability.

Ethical issues in child care are often complicated by the child's inability to take responsibility in their own management decisions and, therefore, their reliance on third parties. This situation is further complicated in those children who have an underlying disability which may influence judgement decisions of the child's surrogate guardians, both toward over or under treatment. This is particularly the case with regard to decisions relating to life support, ongoing and quality of life, appropriate use of limited healthcare resources, and medical research. This article will explore the ethical principles which help to guide the medical management of such difficult cases.

Ethical Issues in Paediatric Practice - Part III: Issues relating to the dying process.

Despite the application of robust ethical principles, complex issues in child care commonly result in ethical dilemmas with no clear answers. This is especially so in those 'life and death' decisions relating to continuing curative therapy or opting for palliative care. As with many situations in paediatrics, these decisions are complicated by difficulties in establishing clear prognostic outcomes both in terms of disease progression and timescales, the child's reliance on third parties, and appropriate use of resources. Great efforts are required to ensure family members are fully informed of the evolving clinical situation relating to their child, and helping them to accept the inevitability of death. Whenever possible, they should be encouraged to plan for their child's death in a manner that is most appropriate for them as an individual family. This article will explore the ethical principles which offer guidance in these situations, and strives toward: i) establishing the acceptance of death by the child and family, ii) ensuring 'quality time' for both family and their dying child and, iii) safeguarding the child's right to die with dignity.

Ethical issues in paediatric practice - part I: general principles.

Clinical problems with ethical implications pose an ever increasing dilemma in everyday medical practice, and this is particularly the case with ethical issues involving children and those unable to take their own decisions. In this editorial we shall review some of the general principles that guide medical ethical problems.

Cardiac malformations associated with the congenital nephrotic syndrome.

The association of cardiac malformation with the congenital nephrotic syndrome (CNS) has been previously reported in only one family. We report four patients with CNS: three with pulmonary valve stenosis (one requiring valvuloplasty) and one with discrete subaortic stenosis requiring surgical resection. We conclude that the cardiac status of all patients with CNS should be reviewed regularly by a paediatrician, with a low threshold for referral to a cardiologist, as flow murmurs due to chronic anaemia may obscure cardiac pathology. It is important to diagnose any associated cardiac lesions as these may require intervention, and may also predispose to the development of bacterial endocarditis if surgical or dental procedures are undertaken without appropriate antibiotic prophylaxis.

Epidemiology and prognostic factors in meningococcal disease in a small island population: Malta 1994-1998.

STUDY OBJECTIVE: To review the epidemiology of meningococcal disease in Malta over the period 1994-1998, and to identify factors at presentation and in the management of meningococcal disease which may influence mortality. DESIGN: All admissions with meningococcal disease to a national hospital in a population-based study over the period 1994-1998 were studied retrospectively. MAIN RESULTS: Fifty-six cases were diagnosed over 1994-1998, the incidence rising from 0.8/100,000 to 7.2/100,000 total population (p < 0.0001). The median time interval from arrival at hospital to administration of parenteral antibiotic decreased over the 5-year period from 4.4 to 1.2 hours (p = 0.025), with no significant change in the case-fatality rate. There was no association between the time interval from arrival at hospital to parenteral antibiotic administration, and mortality. The following features at presentation were associated with increased mortality: older age (p = 0.03), meningococcaemia compared with meningitis (p = 0.05), shock (p < 0.0001), disseminated intravascular coagulation (p = 0.0001), a normal/low white blood cell count (p = 0.0003), a low platelet count (p = 0.0001) and a high serum creatinine (p = 0.003). CONCLUSIONS: The upsurge of cases in the population was accompanied by a decrease in intervention time in the general hospital, probably due to increased awareness of the disease. This study did not show a positive relationship between early in-hospital administration of antibiotics and improved survival, probably because antibiotics were given earlier to those with fulminant disease and, with therefore, an inherently worse outcome. Stratification of cases by severity on admission is recommended in future studies.

Ongoing assessment of nutritional status in children with malignant disease.

The nutritional status of a child on cancer therapy influences both tolerance of and response to treatment. However, it is difficult to assess nutritional status on a daily basis because an accurate quantitation of the calorie intake is difficult. Anthropometric and biochemical parameters are prone to error and often reflect past rather than current nutritional status. In practice, a subjective clinical assessment is usually relied upon. This study objectively appraises the value of such an assessment. Based on clinical symptoms that alter oral intake and absorption of food, a scoring system was designed to assess nutritional status on a day to day basis. A symptom score (SS) of 10 implied "normality"; 0 indicated maximum debility. Over a 2-year period 511 daily scores were recorded in 30 patients aged 0.7-17.5 years. Patients were studied at presentation and during treatment for acute lymphoblastic leukemia (ALL, n = 14; solid tumors receiving megatherapy with autologous bone marrow rescue (ABMR, n = 8), and chemotherapy for different tumors (miscellaneous, n = 8). The SS was compared with other nutritional parameters, including sequential anthropometric indices, serum albumin, insulin-like growth factor-I (IGF-I), IGF binding protein-3 (IGFBP-3), and whole-body protein turnover (WBPT) using [1-(13) C]leucine. The mean SS was reduced at diagnosis for all leukemic patients (median score = 8), improved during first remission (p < 0.002), fell to a minimum during febrile neutropenia (p = 0.0009), and improved with clinical and hematological recovery (p = 0.0009). A reduction in SS was related to fever (p < 0.001) and a fall in neutrophil count (p < 0.001). There was no correlation with anthropometric indices or IGF-I and IGFBP-3 levels. Paired WBPT studies in 9 patients showed that SS correlated well with protein breakdown (p = 0.026). The results suggest that the ongoing nutritional status of children with malignancy undergoing chemotherapy is best assessed using simple clinical parameters.

Changes in protein turnover, IGF-I and IGF binding proteins in children with cancer.

Changes in insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding proteins (IGFBPs) were correlated with protein synthesis and breakdown using [1-13C]leucine before chemotherapy and during subsequent febrile neutropenia (FN) in eight children with cancer, aged 6.3-17.5 y. IGF-I levels were similar to age-matched controls before chemotherapy (mean +/- SEM: 250+/-28 and 228+/-22 microg l(-1), respectively). During FN, IGF-I fell to 156+/-22 microg l(-1) (p = 0.02), and rose to 276+/-27 microg l(-1) with recovery at 6 months (p = 0.004). Similarly, IGFBP-3 decreased from 4.0+/-0.2 mg l(-1) before chemotherapy to 3.0+/-0.3 mg l(-1) during FN (p = 0.01), and returned to 4.1+/-0.2 mg l(-1) at 6 months (p = 0.01). IGF-I correlated with IGFBP-3 (r = +0.7, p < 0.001). Scanning densitometry showed a decrease in IGFBP-3 from 94 to 54% during FN, when the presence of IGFBP-3 protease activity was observed. Compared with normal human serum, IGFBP-2 was elevated throughout the study. IGFBP-1 increased from 14.6+/-3.5 to 30.6+/-2.8 microg l(-1) (p = 0.004), whereas serum insulin decreased from 26.5+/-6.8 to 7.8+/-0.8 mU l(-1) (p = 0.03) before and during FN, respectively. Whilst IGF-I and IGFBP-3 fell, daytime growth hormone increased from 3.3+/-0.6 to 6.7+/-0.8 mU l(-1) (p=0.01), and cortisol from 197+/-48 to 594+/-98 nmol l(-1) (p = 0.005). Albumin decreased from 47+/-2 to 38+/-2 g l(-1) (p = 0.004) and improved to 47+/-2 g l(-1) with recovery (p = 0.003). Protein synthesis increased from 4.5+/-0.4 to 5.0+/-0.6 g kg(-1)d(-1) before chemotherapy and during FN, while protein breakdown rose from 5.4+/-0.4 to 6.3+/-0.4 kg(-1)d(-1). Increasing protein breakdown was related to falling IGF-I and IGFBP-3 levels. Modification of IGFBP-3 by circulating proteolytic activity may alter IGF bioavailability, allowing protein synthesis to increase during periods of severe catabolic stress.

Central venous catheter tip position and malfunction in a paediatric oncology unit.

An audit of 151 central venous catheters (CVCs) in 118 children with malignant disease was carried out over 20 months. The types included 31 valved silastic (Groshong), 58 non-valved silastic (Hickman), and 62 non-valved polyurethane (Cuff Cath) CVCs. There was no difference between the three groups with regard to the clinical diagnosis. The mean patient age at catheter insertion was 5.5 years and the mean weight 21.6 kg. None of the catheter types were associated with an increased risk of problems at insertion, migration, mechanical damage, blockage, sampling, or catheter infection. The incidence of catheter infection was 1.4/1,000 catheter days. Exit-site infection was less frequent with Groshong CVCs (P <0.05), which were in situ for the shortest period. The risk of problems with blood sampling was significantly increased in those catheters whose tip was sited outside the right atrium (P <0.005). For the 60 CVCs removed electively, the mean duration in situ was similar for all catheter types; 43 were removed following a problem. Of these, Groshong catheters were in situ for the shortest period (P = 0.05), probably as a result of delayed anchoring of the cuff. The tip position was the single most important determinant in the correct functioning of CVCs, irrespective of the type of catheter. Intraoperative screening of the tip position at catheter insertion is therefore mandatory for optimal catheter functioning.

Retinoblastoma in association with the chromosome breakage syndromes Fanconi's anaemia and Bloom's syndrome: clinical and cytogenetic findings.

Two children presenting with sporadic unilateral retinoblastoma and exhibiting a high degree of chromosome breakage were noted to have unusual facies, microcephaly and abnormal skin pigmentation. In the first child the pattern of both spontaneous and mitomycin-C-induced chromosome breakage was characteristic of Fanconi's anaemia although the degree of breakage was extreme. She also exhibited a striking increase in X-ray-induced chromosomal damage in G0 lymphocytes as measured by dicentric formation and increase in chromatid-type aberrations. She had a number of typical clinical features, including cafe-au-lait patches and abnormalities involving the kidney; however, she demonstrated neither the hypoplasia of radius and thumb nor the typical aplastic phase of this disorder. At age 22 months the child became anaemic with trilineage myelodysplasia, which was rapidly followed by the development of acute myeloblastic leukaemia. The early onset (at age 4 months) of retinoblastoma may have been associated with the underlying genomic instability. The second child exhibited a pattern of chromosome breakage characteristic of Bloom's syndrome, in addition to a moderate increase in damage induced by mytomycin-C. She had the typical stunted growth and malar hypoplasia of Bloom's syndrome although she did not demonstrate the frequently described erythematous 'butterfly rash' Although patients with Fanconi's anaemia and Bloom's syndrome are recognised to be at an increased risk of cancer, retinoblastoma has not previously been described in patients with either condition. We suggest that underlying recessive chromosome breakage syndromes may be underdiagnosed in paediatric cancer patients, with important implications for prognosis and genetic counselling.

Quality of life in survivors of childhood cancer after megatherapy with autologous bone marrow rescue.

A questionnaire study was carried out in a group of survivors of childhood cancer to assess their quality of life. The questionnaire was sent to 30 survivors who had completed treatment with megatherapy followed by autologous bone marrow rescue at St Bartholomew's Hospital, London. Of the 28 respondents (93%), in 27 (96%) the quality of life was judged to be good, with 11 of these 27 (40%) having no disability whatsoever and a further 9 (33%) reporting only minimal disability. The other 7 patients had moderate to severe disabilities, with pain and depression remaining ongoing problems, and some adolescents felt that they were unable to cope with everyday life alongside their peers. Nine parents and 14 of the children themselves expressed anxiety about the previous illness. The study shows that, by using a postal method, a satisfactory assessment of quality of life in survivors of childhood cancer can be made.

Primary extra-thoracic T-cell non-Hodgkin's lymphoma of childhood. The United Kingdom Children's Cancer Study Group.

Between 60-80% of non-Hodgkin's lymphoma (NHL) of T-cell lineage in children, present with primary mediastinal disease. On current therapy, this and nodal low-stage disease are associated with a relatively favourable outcome. In order to evaluate whether the primary site of disease is a prognostic factor, we examined the clinical characteristics and outcome of 36 children with primary extrathoracic T-cell NHL diagnosed during a 7-year period by the United Kingdom Children's Cancer Study Group. Eight, eight, 11 and nine children had stage I, II, III and IV disease, respectively. The primary site of disease was nodal in 22, skin and subcutaneous tissue in five, abdominal in three, bone in three and at other sites in three. Eighteen (50%) had lymphoblastic, ten (28%) large cell anaplastic (LCA) and seven (19%) pleomorphic large or medium cell (PLC) tumours. In one child the histology was inconclusive. All children with lymphoblastic, three with LCA, three with PLC disease and one with unknown histology were treated on intensive, sustained and continuous leukaemia protocols. Ten, seven with LCA and three with PLC, were treated on regimens of short duration pulsed therapy and one child with PLC with radiotherapy only. The three-year event-free survival (EFS) was 78% for the group as a whole. Those with stage IV lymphoblastic disease had a significantly worse prognosis (p < 0.0005). Primary site of disease, gender, therapeutic regimen and histology were not predictive for survival. In primary extrathoracic T-cell NHL with lymphoblastic histology, leukaemia-like therapy is recommended. For non-lymphoblastic disease, in particular the Ki-1 positive tumours, evidence suggests that short duration pulsed therapy may be optimal.

High incidence of hypertension in children presenting with acute lymphoblastic leukemia.

Although hypertension is a complication of acute lymphoblastic leukemia (ALL), its true incidence in this disease is unknown. In this study the blood pressure profiles in all children newly diagnosed with ALL were reviewed over an 18-month period. Fourteen (46%) from a total of 30 patients were found to be hypertensive at presentation (n = 8) or during induction chemotherapy (n = 6). A patient with significant hypertension developed generalized convulsions; the rest were asymptomatic. Six patients were managed with antihypertensive drugs. Four patients with hypertension had renal enlargement on the initial ultrasound scan, which returned to normal when hematologic remission was achieved. One patient without hypertension had bilateral renal enlargement, but this persisted despite achieving remission. All patients with hypertension were normotensive at follow-up 2 to 18 months after induction chemotherapy. The presence of hypertension before therapy and its association with renal enlargement suggest that the leukemic process is an important etiologic factor. In all cases therapy aggravated or unmasked the elevation in blood pressure. Considering the high incidence of susceptible patients, increased awareness and prompt management may avoid possible life-threatening complications.