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Soluble endothelial adhesion molecules during paediatric cardiovascular surgery with or without cardiopulmonary bypass.

BACKGROUND: Paediatric cardiovascular surgery with or without cardiopulmonary bypass induces a complex pattern of pro- and anti-inflammatory responses. It is suspected that they may contribute to changes on the vascular endothelium. The endothelial response to cardiosurgical trauma and cardiopulmonary bypass, especially in children, has yet to be well established. PATIENTS AND METHODS: We studied 29 children undergoing cardiovascular surgery with cardiopulmonary bypass, comparing them with 21 not undergoing bypass. The groups did not differ significantly with respect to age, sex, weight and preoperative parameters. Blood samples were drawn 24 h before surgery, after onset of anaesthesia, after onset of cardiopulmonary bypass and after rewarming in those undergoing bypass, or immediately after surgery in the control group, 4 h and 2 days after surgery, at discharge, and months after surgery during out-patient follow-up. Serum levels of soluble E-selectin, P-selectin and P-selectin glycoprotein ligand-1 were measured by enzyme-linked immunoassay. RESULTS: Paediatric cardiovascular surgery leads perioperatively to the significant decreases of the serum levels of soluble P- and E-selectin, as well as of soluble P-selectin glycoprotein ligand-1 (all p < 0.05). The time course, and all concentrations, of these molecules were not significantly different with and without bypass. The decreases, however, were more pronounced with cardiopulmonary bypass. Preoperative baseline values were reached months after surgery. CONCLUSION: Endothelial activation of release of adhesion molecules is reduced during paediatric cardiovascular surgery. Endothelial activity is more perturbed with cardiopulmonary bypass and for a long time after surgery.

Biomarkers↗

Development of a cardiac technician led paediatric echocardiographic service--experience from a district general hospital in the United Kingdom.

OBJECTIVES: To report our experience in providing cardiac technician led paediatric echocardiography services in a district general hospital in the United Kingdom. METHODS: We have collected prospectively the numbers of referrals, and the proportion of abnormal echocardiograms, since inception of the service in 2000. In additional, for a period of 12 months, we have audited in detail the patterns of referral to the service, and outcomes, assessing the effect of the service on the outreach clinic run by a visiting paediatric cardiologist. RESULTS: Use of the system resulted in detection of a wide range of abnormalities, with our audit showing that the patients received appropriate management. The total referrals to the service increased 10 fold over the 4 year period of the study. The proportion of abnormal hearts detected by echocardiography, however, dropped from 90 per cent to 16 per cent over the same period. The numbers of patients seen in the outreach cardiology clinic remained unaltered. CONCLUSIONS: Having been proved to be an effective model for the triage of children with suspected congenital cardiac disease, adoption of a cardiac technician led echocardiographic service has seen a dramatic increase in the numbers of echocardiograms requested, without decreasing the workload of the visiting paediatric cardiologist.

Cardiology Service, Hospital↗

Complications of paediatric interventional catheterisation: an analysis of risk factors.

OBJECTIVES: To identify predictive factors of complications occurring during paediatric interventional catheterisation. BACKGROUND: Interventional paediatric catheterisation is still burdened by a substantial risk. Risk factors, however, have rarely been investigated. METHODS: We analysed prospectively 1,022 interventional procedures performed over a period of 8 years, excluding 260 procedures for atrial septostomy. We considered several patient-related variables, specifically age, weight, and gender, type of procedure, times required for fluoroscopy and the overall procedure, technical challenge, and the severity of the clinical condition. We also analysed variables linked to the environment, specifically the date of the examination, whether the operator remained in training, the novelty of the material, any breakdown in the installation, and errors made by the operator. We classified complications as those without clinical consequence, those which proved lethal, those requiring cardiopulmonary resuscitation, elective or emergency surgery, hospitalisation in the intensive care unit, and those leading to recatheterisation. RESULTS: Our average incidence of complications was 4.1 per cent, which did not change significantly during the period of study. Of the patients, 4 died, 7 needed urgent surgery, 5 elective surgery, 3 hospitalisation in intensive care unit, and 8 recatheterisation. Independent risk factors for complications were technical challenge, critical clinical condition, operator in training, operator error, and breakdown of the installation. Young age was not associated with a higher risk of complications. Patients in whom no cause for complication could be found, either related to their own features or the environment, had a risk of complication of 1.4 per cent (95 per cent confidence intervals from 0.7 to 2.5 per cent). CONCLUSIONS: Our data show that variables relating either to the patient or the environment of catheterisation are associated with an increased risk of procedural complications. Knowledge of the risk factors can improve the odds of paediatric interventional catheterisation.

Adolescent↗

Advances in paediatric neuropsychopharmacology: an overview.

This Special Section of Int J Neuropsychopharmacol highlights current progress in paediatric neuropsychopharmacology. Combining critical reviews and, in some cases, new data, specific topics include: biological findings in major depression, sleep dysregulation in depressed youth, cardiovascular and ventilatory dysregulation in panic disorder, paediatric autoimmune neuropsychiatric disorder associated with strep (PANDAS), age of onset as a subtype marker in tic and obsessive--compulsive disorders (OCD), functional and pharmaconeuroanatomy of OCD and the behavioural pharmacokinetics of methylphenidate. In this introductory section, these articles are placed in the context of the state-of-the field and, more specifically, within the framework of recent NIMH initiatives in paediatric neuropsychopharmacology.

Adolescent↗

The use of paediatric chemotherapy protocols at full dose is both a rational and feasible treatment strategy in adults with Ewing's family tumours.

BACKGROUND: Ewing's sarcoma and primitive neuroectodermal tumour (ES/PNET) are rare, limiting opportunities for therapy studies in adults. Chemotherapy regimens adapted from paediatric studies are often used for adults but concerns about poor outcome and treatment toxicity may adversely affect drug dose intensity. We present our experience using a paediatric protocol at full dose. PATIENTS AND METHODS: Records of 34 patients with ES/PNET who received the IVAD chemotherapy regimens were reviewed. Received drug dose intensity, toxicity and survival data were collected. RESULTS: Received dose intensity in 30 evaluable patients was 0.92 compared to the standard IVAD schedule. Myelosuppression was the major toxicity, 83% of patients experienced grade 4 neutropenia. There was no major renal or cardiac toxicity. In patients without metastases at presentation, five-year overall survival was 63% and progression free survival was 39%. Tumour burden at presentation was statistically significantly associated with survival (P = 0.002). The five-year survival rate of 80% in patients presenting with low volume non metastatic disease was equivalent to published paediatric series. CONCLUSIONS: Although the IVAD chemotherapy regimens are myelotoxic in adults, they can be given safely. We recommend that adults with ES/PNET should be included in current multicentre, multidisciplinary treatment studies directed at children.

Adolescent↗

Clinical evaluation of low-flow sevoflurane anaesthesia for paediatric patients.

BACKGROUND: Sevoflurane expenditure, inspired gas humidity, temperature, soda lime temperature, and compounds A and B were measured during high and low fresh gas flow anaesthesia in paediatric patients. METHODS: Sixty ASA 1 or 2 paediatric patients were randomly allocated to two groups: low-flow circle anaesthesia (LFA) patient group (n = 30) and high-flow circle anaesthesia (HFA) patient group (n = 30). Initial fresh gas flow (FGF) was 4l.min-1 of nitrous oxide and 2l.min-1 of oxygen in both groups. This FGF of 6l.min-1 was maintained in the HFA group. After 10 min of HFA, the FGF was reduced to 600 ml.min-1 (nitrous oxide and oxygen 300 ml.min-1 each) in the LFA group. RESULTS: Sevoflurane expenditure during LFA was about 1/7 of that during HFA (3.3 +/- 0.2 ml.h-1.vol.%-1 compared to 22.8 +/- 0.6 ml.h-1.vol.%-1, mean +/- SEM, respectively). Absolute humidity in the LFA patients was 4 times higher than that in the HFA patients (22.8 +/- 2.4 g.m-3 and 5.6 +/- 3.4 g.m-3 respectively). There was no significant difference in the inspiratory gas temperature between the LFA (28.5 +/- 0.6 degrees C) and HFA (26.9 +/- 1.3 degrees C) groups. There was significant difference in the mean highest soda lime temperature between the LFA (35.5 +/- 1.2 degrees C) and HFA (28.7 +/- 1.2 degrees C) groups. The mean highest concentration of compound A was 12.2 +/- 3.8 ppm in the LFA group. The mean highest concentration of compound B was less than 1 ppm. Compounds A and B were below detectable level in the HFA group. CONCLUSION: In conclusion, sevoflurane used for paediatric patients in a circle system with a fresh gas flow of 0.6l.min-1 resulted in a significantly reduced sevoflurane expenditure, higher inspired absolute humidity, but not temperature, compared to a fresh gas flow of 6l.min-1. Low levels of compounds A and B were detected.

Anesthesia, Closed-Circuit↗

The oral manifestations of chronic graft-versus-host disease (cGVHD) in paediatric allogeneic bone marrow transplant recipients.

The oral manifestations of chronic graft-versus-host disease (cGVHD) in eight allogeneic bone marrow transplant (BMT) paediatric recipients were studied clinically, and lip biopsies were performed in seven of them. A prominent lichenoid reaction was observed in four patients, two with accompanying ulceration. Superficial mucoceles were present in three children. Clinically obvious xerostomia was seen in seven patients. Lip biopsies were positive and correlated with the clinical manifestations. Both clinical and histological findings confirmed the diagnosis of cGVHD. In three additional children, with systemic manifestations indicating cGVHD, the oral mucosa was clinically and histologically normal, and the systemic manifestations were, thus, attributed to drug reactions. The above findings indicate the high value of oral examination in diagnosing or confirming paediatric cGVHD. Superficial mucoceles, reported for the first time in paediatric recipients, seem to be important in the early diagnosis of cGVHD.

Adolescent↗

Incubation periods for paediatric AIDS patients.

A recent seroprevalence study of newborns indicates that one in 62 children born in New York City has antibodies to the human immunodeficiency virus (HIV). The distribution of incubation periods for paediatric patients is needed to estimate future AIDS case loads from these seroprevalence data. Current estimates of incubation periods for paediatric patients are based on limited data. We use parametric and non-parametric methods to analyse incubation periods for 215 paediatric patients with AIDS whose only known route of infection is maternal. We conclude that incubation periods are longer than previously reported; that there is a distinct knee in the incubation period distribution at seven months which suggests two risk populations; and that there is an increase in incidence which is consistent with exponential growth.

Acquired Immunodeficiency Syndrome↗

Characteristics and outcomes of paediatric rhegmatogenous retinal detachment treated by segmental scleral buckling plus an encircling element.

PURPOSE: To evaluate the outcome of paediatric rhegmatogenous retinal detachment treated by segmental scleral buckling plus an encircling element. METHODS: A retrospective review was carried out of 15 consecutive paediatric patients (16 eyes). RESULTS: Thirteen of the 15 patients were male (87%), 2 (13%) were female. Their average age was 10.9 years (range 6-18 years; median 10 years). Retinal detachment was caused by trauma in 9 of 16 eyes (56%), high myopia in 5 of 16 eyes (31%) and had an unknown cause in 2 of 16 eyes (13%). Diagnosis was delayed by more than 1 month in 10 of 16 eyes (63%). The visual acuity was 6/60 or worse and the macula was detached on presentation in 13 of 16 eyes (81%). Two of 16 eyes (13%) had mild proliferative vitreoretinopathy. Final reattachment was achieved in all cases. Of 11 eyes with a follow-up of 6 months or more, there was improvement in visual acuity in 7 (63%), and a best-corrected visual acuity of 6/20 or better in 5 (46%). CONCLUSION: Paediatric rhegmatogenous retinal detachment is characterised by a delay in diagnosis and a high degree of macular involvement on presentation. Anatomical reattachment with segmental scleral buckling plus an encircling element was successful in all eyes, and improvement of visual acuity was achieved in one-half of the eyes which had a follow-up of 6 months or more.

Adolescent↗

A phase I study of intravenous liposomal daunorubicin (DaunoXome) in paediatric patients with relapsed or resistant solid tumours.

Anthracyclines are widely used in paediatric oncology, but their use is limited by the risk of cumulative cardiac toxicity. Encapsulating anthracyclines in liposomes may reduce cardiac toxicity and possibly increase drug availability to tumours. A phase I study in paediatric patients was designed to establish the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) after a single course of liposomal daunorubicin, 'DaunoXome', as a 1 h infusion on day 1 of a 21 day cycle. Patients were stratified into two groups according to prior treatment: Group A (conventional) and group B (heavily pretreated patients). Dose limiting toxicity was expected to be haematological, and a two-step escalation was planned, with and without G-CSF support. Pharmacokinetic studies were carried out in parallel. In all, 48 patients aged from 1 to 18 years were treated. Dose limiting toxicity was neutropenia for both groups. Maximum tolerated dose was defined as 155 mg m(-2) for Group A and 100 mg m(-2) for Group B. The second phase with G-CSF was interrupted because of evidence of cumulative cardiac toxicity. Cardiac toxicity was reported in a total of 15 patients in this study. DaunoXome shares the early cardiotoxicity of conventional anthracyclines in paediatric oncology. This study has successfully defined a haematological MTD for DaunoXome, but the significance of this is limited given the concerns of delayed cardiac toxicity. The importance of longer-term follow-up in patients enrolled into phase I studies has been underestimated previously, and may lead to an under-recognition of important adverse events.

Adolescent↗

Conditions for paediatric hearing screening: a survey in 28 Finnish child welfare clinics.

The present Finnish paediatric hearing screening programme was assessed by interviewing nurses and doctors in 28 child welfare clinics responsible for the hearing screening of 18,500 preschool children. Practical issues which might have effects on both performing the screenings and referring the children with abnormal screening results were emphasised. This survey brought out a great variety of deficiencies, which may contribute to the existing delayed diagnosis of hearing impairments. Hearing screening was routinely done 4-12 times per child before school age, instead of the 3 times recommended. Methods with a nonspecific frequency range and sound pressure level were often used. Audiometers were only used in 22 of the 28 clinics, and in only 9 clinics were the audiometers calibrated yearly. The median time of working in the child health care field at that particular health centre was 7 y for the nurses and 6 y for the doctors. Both the nurses and the doctors had numerous responsibilities other than paediatric hearing screening. Implementation of an updating training programme in paediatric audiology for the personnel is recommended.

Child Health Services↗

User charges and the demand for acute paediatric traumatology services.

The city of Helsinki in 1991 introduced moderate patient charges for certain acute paediatric services. This provided the framework for a natural, partially controlled experiment on price elasticity of demand for acute paediatric trauma services. A cross-sectional time-series analysis of a partially controlled natural experiment was done for the period 1989-1994. The findings suggest that moderate user charges may reduce the demand for paediatric trauma services measurably. The effect was diagnosis-specific and, on average, stronger in older than in pre-school children. It probably had a negligible impact on long-term health.

Adolescent↗

Factors influencing nurses' use of nonpharmacological pain alleviation methods in paediatric patients.

The purpose of this study was to describe the factors promoting and hindering nurses' use of nonpharmacological methods in children's surgical pain relief, and demographic variables related to this. The data were collected by a Likert-type questionnaire, which was completed by nurses (n = 162) who were working in one of the paediatric surgical wards located in university hospitals in Finland. The response rate was 99%. Factor analysis was used to analyse the data. According to the results, five promoting factors (nurse's competence, versatile use of pain alleviation methods, workload/time, child's age/ability to cooperate, and parental participation), as well as five hindering factors (nurse's insecurity, beliefs regarding parental roles/child's ability to express pain, heavy workload/lack of time, limited use of pain alleviation methods, and work organizational model/patient turnover rate) were found to influence the nurses' use of nonpharmacological methods. Almost all of the nurses (98%) hoped to make progress in their career and to learn different pain alleviation methods, but less than half of them (47%) agreed that they had obtained sufficient education regarding these methods. Demographic variables such as the nurse's age, education, and work experience were significantly related to certain factors influencing the use of nonpharmacological methods. In conclusion, paediatric patients' surgical pain relief in the hospital was affected more by the nurses' personal characteristics, than by work-related factors or characteristics of the child or the child's parents. The nurses had positive attitudes towards learning different pain alleviation methods, which constitute the basis for the development of pain management in paediatric patients.

Adult↗

Evaluation of personal, environmental and biological exposure of paediatric anaesthetists to nitrous oxide and sevoflurane.

Paediatric anaesthetists are at higher risk of exposure to waste anaesthetic gases, which often exceed set safety limits. Recommended personal diffusive sampling techniques for monitoring exposure to waste anaesthetic gases may not give a true profile of exposure and hence biological sampling may also be necessary. We evaluated the exposure of paediatric anaesthetists to nitrous oxide and sevoflurane as assessed by personal environmental and biological samples. The influence of venue and technique, and the strength of the relationship among the various sampling techniques were analysed. The study found that exposure to nitrous oxide during paediatric anaesthetic inductions is still a major problem, although exposure to sevoflurane was usually within the accepted limits. The type of breathing system used and the presence of scavenging seem to influence this exposure, though surprisingly, the induction technique or the methods of airway control do not. No significant relationship was found between the various biological indicators measured.

Adolescent↗

Thiopurine methyltransferase activity and its relationship to the occurrence of rejection episodes in paediatric renal transplant recipients treated with azathioprine.

AIMS: Azathioprine is a prodrug commonly used in combination therapy to prevent allograft rejection after renal transplantation. After conversion to 6-mercaptopurine, the drug is metabolized into 6-thioguanine nucleotides (6-TGN) and catabolized by thiopurine methyltransferase (TPMT), an enzyme under monogenic control. The aim of this study was to evaluate the inter- and intraindividual variability of red blood cell thiopurine methyltransferase and 6-TGN concentrations and their relationship to the clinical effects of azathioprine in paediatric patients. METHODS: In the present study, the inter- and intraindividual variations in red blood cell TPMT activity and 6-TGN concentrations and their relationship to the actions of azathioprine were evaluated during the first year after renal transplantation in 22 paediatric patients. RESULTS: 6-TGN concentration reached steady-state values after 6 months and correlated negatively with TPMT activity (P=0.004). Initial TPMT activity (median: 20.8 nmol h-1 ml-1, range 7.8-34.6) and 6-TGN concentration at steady-state (median: 80 pmol 8 x 10(8-1) cells, range not detected to 366) were not related to the occurrence of rejection episodes during the period of the study. In contrast, TPMT activity and the percentage difference in TPMT activity from the day of transplantation determined at month 1 were higher in the patients with rejection episodes by comparison with those that did not reject during the first 3 months or the first year following transplantation (P<0.005). CONCLUSIONS: We report a relationship between TPMT activity and occurrence of rejection in paediatric kidney transplant patients undergoing azathioprine therapy. These data suggest a link between high red blood cell TPMT activity and poor clinical outcome probably caused by rapid azathioprine catabolism.

Antimetabolites↗

Enterocytic CYP3A4 in a paediatric population: developmental changes and the effect of coeliac disease and cystic fibrosis.

AIMS: To investigate the effects of age and disease states on the expression and activity of intestinal CYP3A4 in a paediatric population. METHODS: Duodenal biopsies and surgical sections were collected from 104 paediatric patients (age range 2 weeks to 17 years) and from 11 foetuses. An S9 fraction was prepared in each case. CYP3A4 expression was assessed by Western blotting and by immunohistochemistry; activity was measured by the rate of formation of 6beta-hydroxytestosterone from testosterone. Villin expression was used as a marker of enterocyte harvest to normalize CYP3A4 expression and activity data. RESULTS: In the 74 histologically normal paediatric biopsies there were statistically significant increases in CYP3A4 expression (r2 = 0.19, P = 0.001) and activity (r2 = 0.17, P = 0.02) with age. CYP3A4 was practically absent in fetal duodenum and was expressed at relatively low levels in neonates (P < 0.05 between neonates and children > 5 years). Active coeliac disease resulted in significant (P < 0.001) decreases in CYP3A4 expression and activity. CONCLUSIONS: Duodenal CYP3A4 is present at significantly lower levels in neonates and in patients with active coeliac disease. This may have clinical significance with respect to the oral bioavailability of CYP3A4 substrates.

Adolescent↗

Scalp ringworm in south-east London and an analysis of a cohort of patients from a paediatric dermatology department.

BACKGROUND: Scalp ringworm or tinea capitis has become an increasingly important public health issue in the past decade in Great Britain. Recently, certain dermatology departments in London have seen a large increase in tinea capitis in all its forms. OBJECTIVES: The aim of this paper is to present the detailed analysis of a cohort of 277 patients with tinea capitis seen during a 2-year period together with the latest local figures of tinea capitis cases from an inner city paediatric dermatology service. Methods Demographic, clinical and laboratory data were collected prospectively over 2 years from all cases of ringworm in patients seen in a paediatric clinic specially set up for scalp problems. RESULTS: Sixty-two per cent of 277 cases of scalp ringworm were caused by Trichophyton tonsurans, occurring mainly (91%) in patients with Afro-Caribbean hair type, more often in boys (68%), and in the 3-8 year olds (70%). Only 7% of the patients had received appropriate treatment with oral griseofulvin. An additional 156 cases from the general paediatric dermatology clinic showed 91%T. tonsurans infections. CONCLUSIONS: The prevalence of scalp ringworm appears to be reaching epidemic proportions in certain areas that include south-east London. The clinical problem is not yet well recognized by local general practitioners.

Age Distribution↗

Erythrocyte autoantibodies in paediatric patients with sickle cell disease receiving transfusion therapy: frequency, characteristics and significance.

The formation of erythrocyte autoantibodies following transfusion therapy has been described in case reports and small series. To determine the frequency, serological characteristics, and clinical significance of this phenomenon in paediatric patients with sickle cell disease, we analysed the patient database at the Duke University Pediatric Hematology Clinic. We identified children who received multiple erythrocyte transfusions, then reviewed clinical records to identify children who developed erythrocyte autoantibodies in association with transfusions. Among 184 paediatric patients who received multiple erythrocyte transfusions, 14 children (7.6%) developed warm (IgG) erythrocyte autoantibodies. Median transfusion exposure at the time of autoantibody formation was 24 erythrocyte units, range 3-341 units. The autoantibody reacted as a panagglutinin in 11 cases but had anti-e specificity in three patients. Surface complement also was detected in five patients. Clinically significant haemolysis was documented in four patients, each of whom had both surface IgG and C3 detected. The development of erythrocyte autoantibodies was associated with the presence of erythrocyte alloantibodies. Formation of warm erythrocyte autoantibodies in association with transfusions is not rare in paediatric patients with sickle cell disease. Clinicians should be aware of this complication and recognize that the presence of surface C3 is often associated with significant haemolysis.

Adolescent↗