Showing papers by "Great Ormond Street Hospital published in 2004"

HIV evolution: CTL escape mutation and reversion after transmission.

Abstract: Within-patient HIV evolution reflects the strong selection pressure driving viral escape from cytotoxic T-lymphocyte (CTL) recognition. Whether this intrapatient accumulation of escape mutations translates into HIV evolution at the population level has not been evaluated. We studied over 300 patients drawn from the B- and C-clade epidemics, focusing on human leukocyte antigen (HLA) alleles HLA-B57 and HLA-B5801, which are associated with long-term HIV control and are therefore likely to exert strong selection pressure on the virus. The CTL response dominating acute infection in HLA-B57/5801-positive subjects drove positive selection of an escape mutation that reverted to wild-type after transmission to HLA-B57/5801-negative individuals. A second escape mutation within the epitope, by contrast, was maintained after transmission. These data show that the process of accumulation of escape mutations within HIV is not inevitable. Complex epitope- and residue-specific selection forces, including CTL-mediated positive selection pressure and virus-mediated purifying selection, operate in tandem to shape HIV evolution at the population level.

CD4+CD25bright Regulatory T Cells Actively Regulate Inflammation in the Joints of Patients with the Remitting Form of Juvenile Idiopathic Arthritis

Abstract: This study investigates the role of CD4(+)CD25(+) regulatory T cells during the clinical course of juvenile idiopathic arthritis (JIA). Persistent oligoarticular JIA (pers-OA JIA) is a subtype of JIA with a relatively benign, self-remitting course while extended oligoarticular JIA (ext-OA JIA) is a subtype with a much less favorable prognosis. Our data show that patients with pers-OA JIA display a significantly higher frequency of CD4(+)CD25(bright) T cells with concomitant higher levels of mRNA FoxP3 in the peripheral blood than ext-OA JIA patients. Furthermore, while numbers of synovial fluid (SF) CD4(+)CD25(bright) T cells were equal in both patient groups, pers-OA JIA patients displayed a higher frequency of CD4(+)CD25(int) T cells and therefore of CD4(+)CD25(total) in the SF than ext-OA JIA patients. Analysis of FoxP3 mRNA levels revealed a high expression in SF CD4(+)CD25(bright) T cells of both patient groups and also significant expression of FoxP3 mRNA in the CD4(+)CD25(int) T cell population. The CD4(+)CD25(bright) cells of both patient groups and the CD4(+)CD25(int) cells of pers-OA JIA patients were able to suppress responses of CD25(neg) cells in vitro. A markedly higher expression of CTLA-4, glucocorticoid-induced TNFR, and HLA-DR on SF CD4(+)CD25(bright) T regulatory (Treg) cells compared with their peripheral counterparts suggests that the CD4(+)CD25(+) Treg cells may undergo maturation in the joint. In correlation with this mature phenotype, the SF CD4(+)CD25(bright) T cells showed an increased regulatory capacity in vitro compared with peripheral blood CD4(+)CD25(bright) T cells. These data suggest that CD4(+)CD25(bright) Treg cells play a role in determining the patient's fate toward either a favorable or unfavorable clinical course of disease.

Androgen and psychosexual development: Core gender identity, sexual orientation, and recalled childhood gender role behavior in women and men with congenital adrenal hyperplasia (CAH)

Abstract: We assessed core gender identity, sexual orientation, and recalled childhood gender role behavior in 16 women and 9 men with congenital adrenal hyperplasia (CAH) and in 15 unaffected female and 10 ...

A randomized trial of parenteral methotrexate comparing an intermediate dose with a higher dose in children with juvenile idiopathic arthritis who failed to respond to standard doses of methotrexate.

Abstract: Objective To compare the safety and efficacy of parenteral methotrexate (MTX) at an intermediate dosage (15 mg/m2/week) versus a higher dosage (30 mg/m2/week) in patients with polyarticular-course juvenile idiopathic arthritis (JIA) who failed to improve while receiving standard dosages of MTX (8–12.5 mg/m2/week). Methods In the screening phase, 595 patients who were newly started on a standard dose of MTX were followed up for 6 months. Subsequently, the nonresponders, defined according to the American College of Rheumatology (ACR) pediatric 30% improvement criteria (pediatric 30), were randomized to receive an intermediate dose or higher dose of parenteral MTX for an additional 6 months. Improvement in the screening and randomization phase was defined by the ACR pediatric 30 response, as well as by the 50% and 70% response levels (ACR pediatric 50 and ACR pediatric 70, respectively). Results In the screening phase, after receiving standard doses of MTX, 430 patients (72%) improved according to the ACR pediatric 30, while 360 (61%) met the ACR pediatric 50 and 225 (38%) met the ACR pediatric 70; among these patients, 69 (12%) also met the definition of complete disease control. Of the 133 nonresponders, 80 were randomized to receive an intermediate dose or higher dose of MTX. In the randomization phase, the ACR pediatric 30 response rate was 25 of 40 children (62.5%) in the intermediate-dose group versus 23 of 40 children (57.5%) in the higher-dose group. An ACR pediatric 50 response rate was attained by 23 patients (57.5%) receiving an intermediate dose versus 22 (55%) in the higher-dose group. An ACR pediatric 70 response rate was seen in 18 children (45%) receiving an intermediate dose versus 19 (47.5%) receiving a higher dose. Five children (12.5%) in the intermediate-dose group versus 4 (10%) receiving the higher dose of MTX also met the definition of complete disease control. None of the intergroup differences in response rate were significant. There were no significant differences in the frequency of adverse events or laboratory abnormalities between the 2 randomized groups. Conclusion This study shows that the plateau of efficacy of MTX in JIA is reached with parenteral administration of 15 mg/m2/week and that a further increase in dosage is not associated with any additional therapeutic benefit. MTX should be administered for up to 9–12 months to appreciate its full therapeutic effect.

Mutations in the transmembrane natriuretic peptide receptor NPR-B impair skeletal growth and cause acromesomelic dysplasia, type Maroteaux

Abstract: The homodimeric transmembrane receptor natriuretic peptide receptor B (NPR-B [also known as guanylate cyclase B, GC-B, and GUC2B]; gene name NPR2) produces cytoplasmic cyclic GMP from GTP on binding its extracellular ligand, C-type natriuretic peptide (CNP). CNP has previously been implicated in the regulation of skeletal growth in transgenic and knockout mice. The autosomal recessive skeletal dysplasia known as "acromesomelic dysplasia, type Maroteaux" (AMDM) maps to an interval that contains NPR2. We sequenced DNA from 21 families affected by AMDM and found 4 nonsense mutations, 4 frameshift mutations, 2 splice-site mutations, and 11 missense mutations. Molecular modeling was used to examine the putative protein change brought about by each missense mutation. Three missense mutations were tested in a functional assay and were found to have markedly deficient guanylyl cyclase activity. We also found that obligate carriers of NPR2 mutations have heights that are below the mean for matched controls. We conclude that, although NPR-B is expressed in a number of tissues, its major role is in the regulation of skeletal growth.

Encephalitis lethargica syndrome: 20 new cases and evidence of basal ganglia autoimmunity

Abstract: Summary In 1916, von Economo first described encephalitis lethargica (EL), a CNS disorder presenting with pharyngitis followed by sleep disorder, basal ganglia signs (particularly parkinsonism) and neuropsychiatric sequelae. Since the 1916‐1927 epidemic, only sporadic cases have been described. Pathological studies revealed an encephalitis of the midbrain and basal ganglia, with lymphocyte (predominantly plasma cell) infiltration. The EL epidemic occurred during the same time period as the 1918 influenza pandemic, and the two outbreaks have been linked in the medical literature. However, von Economo and other contemporary scientists thought that the 1918 influenza virus was not the cause of EL. Recent examination of archived EL brain material has failed to demonstrate influenza RNA, adding to the evidence that EL was not an invasive influenza encephalitis. By contrast, the findings of intrathecal oligoclonal bands (OCB) and beneficial effects of steroid treatments have provoked the hypothesis that EL may be immune-mediated. We have recently seen 20 patients with a similar EL phenotype, 55% of whom had a preceding pharyngitis. The patients had remarkable similarity to the historical descriptions of EL: sleep disorder (somnolence, sleep inversion or insomnia), lethargy, parkinsonism, dyskinesias and neuropsychiatric symptoms. CSF examination commonly showed elevated protein and OCB (75 and 69% respectively). Investigation found no evidence of viral encephalitis or other recognized causes of rapid-onset parkinsonism. MRI of the brain was normal in 60% but showed inflammatory changes localized to the deep grey matter in 40% of patients. We investigated the possibility that this phenotype could be a postinfectious autoimmune CNS disorder, and therefore similar to Sydenham’s chorea. Anti-streptolysin-O titres were elevated in 65% of patients. Furthermore, western immunoblotting showed that 95% of EL patients had autoantibodies reactive against human basal ganglia antigens. These antibodies were also present in the CSF in four patients tested. By contrast, antibodies reactive against the basal ganglia were found in only 2‐4% of child and adult controls (n = 173, P < 0.0001). Rather than showing polyspecific binding, these antibodies bound to common neural autoantigens of molecular weight 40, 45, 60 and 98 kDa. Regional tissue comparisons showed that the majority of these autoantigens were specific to or enriched in CNS tissue. Immunohistochemistry with secondary staining localized antibody binding to neurons rather than glial populations. Further investigation is required to determine whether these antibodies affect neuronal function (i.e. whether they are pathogenic anti-neuronal antibodies). Histopathology in one case demonstrated striatal encephalitis with perivenous Band T-lymphocytic infiltration. We believe an EL-like syndrome is still prevalent, and propose that this syndrome may be secondary to autoimmunity against deep grey matter neurons.

A systematic review of the epidemiology of status epilepticus

Abstract: Population-based data on the incidence, aetiology, and mortality associated with status epilepticus (SE) are required to develop preventative strategies for SE. Through a systematic review, we aimed to assess the methodological quality as well as similarities, and differences between available population based studies in order to arrive at conclusions on the epidemiology of SE. All population-based studies where primary outcome was incidence, aetiology or mortality of SE were identified through a systematic search and synthesized. Methodological quality of studies were independently rated by two examiners using a unique scoring system. Seven population-based projects on SE yielding nine published reports and five abstracts were reviewed. Quality scores were in the range of 19-34 with a possible maximum of 40 (kappa scores 0.67-1.0). The incidence of SE has a bimodal distribution with peaks in children aged less than a year and the elderly. Most SE were acute symptomatic. Short-term mortality was 7.6-22% and long-term mortality was 43%. Age and aetiology were the major determinants of mortality. There are few population-based studies on SE but most are of good quality. Most studies are primarily or exclusively based on adult populations. There is limited information on the association of ethnicity and socio-economic status and SE.

Permanent consequences in Langerhans cell histiocytosis patients: a pilot study from the Histiocyte Society-Late Effects Study Group.

Abstract: Background Permanent consequences (PC) are often described among subjects with Langerhans cell histiocytosis (LCH) but data on the real incidence are scarce. Within the Histiocyte Society (HS), and in order to design a definitive late effects study, a retrospective survey was organized to describe the prevalence of PC among long-term survivors of LCH. Methods Nine institutions contributed with their LCH patients having a minimum follow-up of 3 years. Information was collected on their disease-history, and on type and date of onset of any PC. Because of the retrospective type of this study, it was accepted that each institution might have used different criteria to assess PC. Results One hundred eighty-two subjects were registered and in 95 (52%) at least 1 PC was reported. For some specific PC (e.g., anterior pituitary dysfunction) information was too scarce to provide reliable data. PC were more frequent among subjects with multisystem (MS) disease (71%), compared to those with single system (SS) disease (24%); P < 0.0001. The most frequently reported PC were diabetes insipidus (DI) (24%) orthopedic abnormalities (20%), hearing loss (13%), and neurological consequences (11.0%). Analysis of cumulative risk showed that some types of PC may become manifest more than 10 years from diagnosis. Conclusions This survey on selected cases of LCH survivors has confirmed that late sequels are frequent, and that they are even more common among those with MS LCH. Our findings highlight the need for long-term and patient-oriented follow-up in children with LCH. © 2004 Wiley-Liss, Inc.

Psychological impact of genetic testing for familial hypercholesterolemia within a previously aware population: a randomized controlled trial.

Abstract: This trial tests the hypothesis that confirming a clinical diagnosis of familial hypercholesterolemia (FH) by finding a genetic mutation reduces patients' perceptions of control over the disease and adherence to risk-reducing behaviors. Three hundred forty-one families, comprising 341 hypercholesterolemia probands and 128 adult relatives, were randomized to one of two groups: (a) routine clinical diagnosis; (b) routine clinical diagnosis plus genetic testing (mutation searching in probands and direct gene testing in relatives). The main outcome measures were perceptions of control over hypercholesterolemia, adherence to cholesterol-lowering medication, diet, physical activity, and smoking. There was no support for the main hypothesis: finding a mutation had no impact on perceived control or adherence to risk-reducing behavior (all P-values > 0.10). While all groups believed that lowering cholesterol was an effective way of reducing the risk of a heart attack, participants in whom a mutation was found believed less strongly in the efficacy of diet in reducing their cholesterol level (P = 0.02 at 6 months) and showed a trend in believing more strongly in the efficacy of cholesterol-lowering medication (P = 0.06 at 6 months). In conclusion, finding a mutation to confirm a clinical diagnosis of FH in a previously aware population does not reduce perceptions of control or adherence to risk-reducing behaviors. The pattern of findings leads to the new hypothesis that genetic testing does not affect the extent to which people feel they have control over a condition, but does affect their perceptions of how control is most effectively achieved. Further work is needed to determine whether similar results will be obtained in populations with little previous awareness of their risks.

Management of child and adolescent eating disorders: the current evidence base and future directions

Abstract: Although eating disorders in children and adolescents remain a serious cause of morbidity and mortality, the evidence base for effective interventions is surprisingly weak. The adult literature is growing steadily, but this is mainly with regard to psychological therapies for bulimia nervosa and to some extent in the field of pharmacotherapy. This review summarises the recent research literature covering management in three areas, namely physical management, psychological therapies, and service issues, and identifies prognostic variables. Findings from the adult literature are presented where there is good reason to believe that these might be applied to younger patients. Evidence-based good practice recommendations from published clinical guidelines are also discussed. Suggestions for future research are made, focusing on 1) the need for trials of psychological therapies in anorexia nervosa, 2) applications of evidence-based treatments for adult bulimia nervosa to the treatment of adolescents, and 3) clarification of the benefits and costs of different service models.

Re-thinking family-centred care across the continuum of children's healthcare.

Abstract: Background The terms family-centred care (FCC) and family-centred services (FCS) are used interchangeably across the continuum of children's healthcare to encompass concepts of: parental participation in children's healthcare; partnership and collaboration between the healthcare team and parents in decision-making; family-friendly environments that normalize as much as possible family functioning within the healthcare setting; and care of family members as well as of children. However, authors from different professional and policy perspectives have used different definitions and literatures when arguing the evidence for FCC and FCS. Method A critical literature review and theoretical discussion exploring common concepts and issues forming the basis for a research agenda further strengthening of the evidence base for FCC. A systematic identification of constructs, concepts and empirical indicators is developed and applied to exemplars in pain and asthma that span the continuum of children's healthcare across acute and community settings. Conclusions The extent to which the concepts are supported by research and applied in practice remains unclear. We propose that re-thinking of FCC is required in order to develop a more coherent programme of research into the application of FCC theory in children's healthcare.

Clinical validation of the paediatric pain profile.

Abstract: The Paediatric Pain Profile (PPP) is a 20–item behaviour rating scale designed to assess pain in children with severe neurological disability. We assessed the validity and reliability of the scale in 140 children (76 females, mean age 9 years 11 months, SD 4 years 7 months; range 1 to 18 years), unable to communicate through speech or augmentative communication. Parents used the PPP to rate retrospectively their child's behaviour when‘at their best’and when in pain. To assess interrater reliability, two raters concurrently observed and individually rated each child's behaviour. To assess construct validity and responsiveness of the scale, behaviour of 41 children was rated before and for four hours after administration of an‘as required’analgesic. Behaviour of 30 children was rated before surgery and for five days after. Children had significantly higher scores when reported to have pain than‘at their best’and scores increased in line with global evaluations of pain. Internal consistency ranged from 0.75 to 0.89 (Cronbach's alpha) and interrater reliability from 0.74 to 0.89 (intraclass correlation). Sensitivity (1.00) and specificity (0.91) were optimized at a cut-off of 14/60. PPP score was significantly greater before administration of the analgesic than after (paired-sample t-tests, p < 0.001). Though there was no significant difference in mean pre- and postoperative scores, highest PPP score occurred in the first 24 hours after surgery in 14 (47%) children. Results suggest that the PPP is reliable and valid and has potential for use both clinically and in intervention research.

Ensuring quality information for patients: development and preliminary validation of a new instrument to improve the quality of written health care information.

Abstract: BACKGROUND: Despite the recent focus on improving the quality of patient information, there is no rigorous method of assessing quality of written patient information that is applicable to all information types and that prescribes the action that is required following evaluation. OBJECTIVE: The aims of this project were to develop a practical measure of the presentation quality for all types of written health care information and to provide preliminary validity and reliability of the measure in a paediatric setting. METHODS: The Ensuring Quality Information for Patients (EQIP) tool was developed through a process of item generation, testing for concurrent validity, inter-rater reliability and utility. Patient information managers and health care professionals tested EQIP in three annual audits of health care leaflets produced by a children's hospital. RESULTS: The final tool comprised 20 items. Kendall's tau B rank correlation between EQIP and DISCERN was 0.56 (P = 0.001 ). There was strong agreement be tween intuitive rating and the EQIP score (Kendall's tau B = 0.78, P = 0.009). Internal consistency using Cronbach's alpha was 0.80. There was good agreement between pairs of raters (mean kappa = 0.60; SD = 0.18) with no differences based on types of leaflets. Audits showed significant improvement in the number of leaflets achieving a higher quality EQIP rating over a 3-year period. CONCLUSIONS: EQIP demonstrated good preliminary validity, reliability and utility when used by patient information managers and healthcare professionals for a wide variety of written health care information. EQIP uniquely identifies actions to be taken as a result of the quality assessment. Use of EQIP improved the quality of written health care information in a children's hospital. Wider evaluation of EQIP with written information for other populations and settings is recommended

Maturation of DC is associated with changes in motile characteristics and adherence.

Abstract: Migration of dendritic cells (DC) from sentinel sites to lymphoid tissue entails the initiation and coordination of a complex series of cytoskeletal rearrangements resulting in polarised protrusion, formation of new adhesion points, and detachment. Although many diverse receptor-ligand interactions stimulating DC maturation and migration have been identified, the changes that occur in the structure of the actin cytoskeleton during these processes have received little attention. When derived in vitro, immature DC floated in clumps, and upon addition of maturation stimuli such as lipopolysaccharide (LPS), they rapidly adhered, developed polarity, and assembled actin-rich structures known as podosomes at the leading edge of the cell. Podosome assembly was associated with the specific recruitment of beta2 integrins, which in the absence of the Wiskott Aldrich Syndrome protein (WASp), did not occur. As maturation progressed, normal DC once again became rounded and devoid of podosomes. This change in morphology was closely associated with a quantitatively reduced ability to adhere to fibronectin or ICAM-1-coated surfaces. In immature DC, failure to form podosomes or selective inhibition of the CD18 component of podosomes resulted in a similarly reduced ability to adhere to ICAM-1, indicating that podosomes, through CD18, are necessary for tight adhesion to this ligand. We, therefore, propose that podosomes provide an essential link between directional cell protrusion and achievement of DC translocation by establishing new dynamic anchor points at the front of the cell. The temporal regulation of podosome assembly during DC maturation also suggests that they may be most critical for early movement, perhaps during transmigration of lymphatic endothelium. (C) 2004 Wiley-Liss, Inc.

Increased prevalence of epilepsy associated with severe falciparum malaria in children.

Abstract: Summary: Purpose: Multiple, prolonged, generalized, or focal seizures are common in children with severe malaria, with or without coma. In other contexts, such seizures have been associated with the development of epilepsy. The relation between falciparum malaria and epilepsy is undetermined; thus we measured the prevalence and characteristics of epilepsy in children with a history of severe malaria. Methods: We took a detailed epilepsy history from the parents of 487 children (aged 6–9 years) to compare the prevalence of epilepsy between three exposure groups: children with a history of cerebral malaria (CM), malaria and complicated seizures (M/S), or those unexposed to either complication. Each child had an EEG and was classified as having active, inactive, or no epilepsy. Results: An increased prevalence of epilepsy was seen in children previously admitted with CM [9.2%; OR, 4.4; 95% confidence interval (CI), 1.4–13.7] or M/S (11.5%; OR, 6.1; 95% CI, 2.0–18.3) compared with the unexposed group (2.2%). The most commonly reported seizure types were tonic–clonic (42%), focal becoming secondarily generalized (16%), and both (21%). Twenty-six percent of the active epilepsy group initially had EEG abnormalities. Conclusions: These results suggest that children exposed to CM or M/S have an increased propensity for epilepsy relative to children unexposed to these complications. The prevalence of epilepsy associated with CM is similar to that reported after other severe encephalopathies. The prevalence associated with M/S is more than twice that reported after complicated febrile seizures.

The post-transplant lymphoproliferative disorder—a literature review

Abstract: The Epstein-Barr virus (EBV)-induced post-transplant lymphoproliferative disorder (PTLD) affects 1%–10% of all paediatric renal transplant recipients. This is a heterogeneous group of conditions characterised by EBV-driven proliferation of B-lymphocytes in the face of impaired T-cell immune surveillance. The risk factors predisposing to PTLD are becoming better understood, but its pathogenesis and myriad of clinical and histological features remain poorly defined. While new treatment modalities are being tried with variable success, regular EBV surveillance and carefully monitored reduction of immunosuppression remain the mainstay of treatment. In this review, we have presented the current knowledge of this increasingly common complication in renal transplant recipients.

What is the daily practice of mechanical ventilation in pediatric intensive care units? A multicenter study

Abstract: To describe the daily practice of mechanical ventilation (MV), and secondarily, its outcome in pediatric intensive care units (PICUs) Prospective cohort of infants and children who received MV for at least 12 h Thirty-six medical surgical PICUs All consecutive patients admitted to the PICUs during 2-month period Of the 1893 patients admitted, 659 (35%) received MV for a median time of 4 days (25th percentile, 75%: 2, 6) Median of age was 13 months (25th percentile, 75%: 5, 48) Common indications for MV were acute respiratory failure (ARF) in 72% of the patients, altered mental status in 14% of the patients, and ARF on chronic pulmonary disease in 10% of the patients Median length of stay in the PICUs was 8 days (25th percentile, 75%: 5, 13) Overall mortality rate in the PICUs was 15% (confidence interval 95%: 13–18) for the entire population, 50% (95% CI: 25–74) in patients who received MV because of acute respiratory distress syndrome, 24% (95% CI: 16–35) in patients who received MV for altered mental status and 16% (95% CI: 9–29) in patients who received MV for ARF on chronic pulmonary disease One in every 3 patients admitted to the PICUs requires ventilatory support The ARF was the most common reason for MV, and survival of unselected infants and children receiving MV for more than 12 h was 85%

Autologous stem cell transplantation for refractory juvenile idiopathic arthritis: analysis of clinical effects, mortality, and transplant related morbidity

Abstract: Objective: To evaluate the safety and efficacy of autologous stem cell transplantation (ASCT) for refractory juvenile idiopathic arthritis (JIA). Design: Retrospective analysis of follow up data on 34 children with JIA who were treated with ASCT in nine different European transplant centres. Rheumatological evaluation employed a modified set of core criteria. Immunological reconstitution and infectious complications were monitored at three month intervals after transplantation. Results: Clinical follow up ranged from 12 to 60 months. Eighteen of the 34 patients (53%) with a follow up of 12 to 60 months achieved complete drug-free remission. Seven of these patients had previously failed treatment with anti-TNF. Six of the 34 patients (18%) showed a partial response (ranging from 30% to 70% improvement) and seven (21%) were resistant to ASCT. Infectious complications were common. There were three cases of transplant related mortality (9%) and two of disease related mortality (6%). Conclusions: ASCT in severely ill patients with JIA induces a drug-free remission of the disease and a profound increase in general wellbeing in a substantial proportion of patients, but the procedure carries a significant mortality risk. The following adjustments are proposed for future protocols: (1) elimination of total body irradiation from the conditioning regimen; (2) prophylactic administration of antiviral drugs and intravenous immunoglobulins until there is a normal CD4+ T cell count.

Increased incidence and severity of the systemic inflammatory response syndrome in patients deficient in mannose-binding lectin

Abstract: To determine whether pediatric PICU patients with mannose-binding lectin (MBL) gene polymorphisms associated with low levels of the functional protein have an increased risk of developing sepsis and SIRS A prospective, observational cohort study in a 22-bed PICU in a tertiary referral centre One hundred consecutive admissions to a PICU with at least one organ system failure longer than 12 h Patients were classified into those with infectious or non-infectious insults as the primary reason for intensive care admission Patients were followed to determine which developed sepsis or non-infection related SIRS using standard criteria Of the 100 patients 50 had infectious and 50 had non-infectious insults as the precipitant for admission 42 patients had variant MBL alleles (determined by MBL-2 gene exon 1 and promoter polymorphisms) and were significantly over-represented amongst the 59 patients that developed SIRS This effect was not explained by differences in age, sex or ethnicity and was seen in both the infection and non-infection subgroups In patients with infection, variant MBL alleles were associated with increased systemic response (2/15 with localised infection, 10/19 with sepsis and 12/16 with septic shock) MBL serum levels showed close concordance with the genotype and indicated that MBL levels less than 1000 ng/ml are associated with a greatly increased risk of SIRS MBL-2 exon 1 polymorphisms with low serum levels of functional MBL protein are associated with a greatly increased risk of developing SIRS and of progression from infection to sepsis and septic shock in paediatric ICU patients

Nonsurgical pulmonary valve replacement: why, when, and how?

Abstract: Percutaneous transcatheter interventions for valve replacement or implantation is one of the most exciting developments in the field of interventional cardiology. Valvular stenosis has been treated by balloon dilatation with early and late results; however, treatment for valvular regurgitation has remained surgical until now. Most new designs have been investigated for implantation of valves in the left or right ventricular outflow tracts. Patients with surgery on the right ventricular outflow tract for congenital heart disease constitute the most common group for reoperations during late follow-up. Surgical pulmonary valve replacement can be performed with low mortality; however, it sets up a substrate for future operations. Also, the risk of cardiopulmonary bypass, infection, bleeding, and ventricular dysfunction remains. A transcatheter technique is likely to have more acceptance and may expand the indications for early intervention for right ventricular outflow tract dysfunction.

Asymptomatic and Symptomatic Excretion of Noroviruses during a Hospital Outbreak of Gastroenteritis

Abstract: During an investigation of a hospital outbreak of norovirus gastroenteritis identified as being caused by a recombinant genogroup II (rGII-3a) strain, fecal specimens collected from asymptomatic staff and patients were tested by nested PCR. A GII-4 norovirus strain, the predominant strain associated with outbreaks in hospitals over the last few years, was detected in 26 and 33% of asymptomatic staff and patients, respectively. No rGII-3a (Harrow/Mexico) norovirus strains were detected in the samples of asymptomatic staff or patients.