children
not annotated - annotated - LINNAEUS only
20869315
Drug interactions in childhood cancer.
Children with cancer are increasingly benefiting from new treatment strategies and advances in supportive care, as shown by improvements in both survival and quality-of-life. However, the continuous emergence of new cancer drugs and supportive-care drugs has increased the possibility of harmful drug interactions; health-care providers need to be very cautious when combining drugs. We discuss the most common interactions between chemotherapeutic drugs and supportive-care drugs-such as anticonvulsants, antiemetics, uric-acid-lowering compounds, acid suppressants, antimicrobials, and pain-management medications in paediatric patients. We also review the interactions between chemotherapy drugs and food and herbal supplements, and provide recommendations to avoid unwanted and potentially fatal interactions in children with cancer. Because of the constant release of new drugs, health-care providers need to check the most recent references before making recommendations about drug interactions.
20980510
Assembly and immunological properties of Newcastle disease virus-like particles containing the respiratory syncytial virus F and G proteins.
Human respiratory syncytial virus (RSV) is a serious respiratory pathogen in infants and young children as well as elderly and immunocompromised populations. However, no RSV vaccines are available. We have explored the potential of virus-like particles (VLPs) as an RSV vaccine candidate. VLPs composed entirely of RSV proteins were produced at levels inadequate for their preparation as immunogens. However, VLPs composed of the Newcastle disease virus (NDV) nucleocapsid and membrane proteins and chimera proteins containing the ectodomains of RSV F and G proteins fused to the transmembrane and cytoplasmic domains of NDV F and HN proteins, respectively, were quantitatively prepared from avian cells. Immunization of mice with these VLPs, without adjuvant, stimulated robust, anti-RSV F and G protein antibody responses. IgG2a/IgG1 ratios were very high, suggesting predominantly T(H)1 responses. In contrast to infectious RSV immunization, neutralization antibody titers were robust and stable for 4 months. Immunization with a single dose of VLPs resulted in the complete protection of mice from RSV replication in lungs. Upon RSV intranasal challenge of VLP-immunized mice, no enhanced lung pathology was observed, in contrast to the pathology observed in mice immunized with formalin-inactivated RSV. These results suggest that these VLPs are effective RSV vaccines in mice, in contrast to other nonreplicating RSV vaccine candidates.
21163445
Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis.
Since its discovery in 2007, the encephalitis associated with antibodies against the N-methyl-D-aspartate receptor (NMDAR) has entered the mainstream of neurology and other disciplines. Most patients with anti-NMDAR encephalitis develop a multistage illness that progresses from psychosis, memory deficits, seizures, and language disintegration into a state of unresponsiveness with catatonic features often associated with abnormal movements, and autonomic and breathing instability. The disorder predominantly affects children and young adults, occurs with or without tumour association, and responds to treatment but can relapse. The presence of a tumour (usually an ovarian teratoma) is dependent on age, sex, and ethnicity, being more frequent in women older than 18 years, and slightly more predominant in black women than it is in white women. Patients treated with tumour resection and immunotherapy (corticosteroids, intravenous immunoglobulin, or plasma exchange) respond faster to treatment and less frequently need second-line immunotherapy (cyclophosphamide or rituximab, or both) than do patients without a tumour who receive similar initial immunotherapy. More than 75% of all patients have substantial recovery that occurs in inverse order of symptom development and is associated with a decline of antibody titres. Patients' antibodies cause a titre-dependent, reversible decrease of synaptic NMDAR by a mechanism of crosslinking and internalisation. On the basis of models of pharmacological or genetic disruption of NMDAR, these antibody effects reveal a probable pathogenic relation between the depletion of receptors and the clinical features of anti-NMDAR encephalitis.
21163447
Acute encephalopathy with inflammation-mediated status epilepticus.
Fever-induced refractory epileptic encephalopathy in school-aged children (FIRES), and idiopathic hemiconvulsion-hemiplegia syndrome (IHHS) are both triggered by fever, although evidence for a causal microorganism or an autoimmune phenomenon is lacking. FIRES begins in school age with status epilepticus lasting several weeks, involves perisylvian areas including mesial temporal structures, and is followed by pharmacoresistant epilepsy with major cognitive deterioration. IHHS begins in infancy with unilateral clonic status epilepticus and is followed by hemiplegia with pharmacoresistant epilepsy. The aetiology of FIRES and IHHS remains unknown, although clinical features and experimental models point to a likely vicious cycle involving inflammation and seizure activity that depends on the stage of brain maturation. We therefore propose to group these conditions under the concept of acute encephalopathy with inflammation-mediated status epilepticus. In addition to preliminary but encouraging clinical observations, there are theoretical reasons to consider the ketogenic diet as an early means to control both seizures and inflammation.
21227494
Reproductive health, and child health and nutrition in India: meeting the challenge.
India, with a population of more than 1 billion people, has many challenges in improving the health and nutrition of its citizens. Steady declines have been noted in fertility, maternal, infant and child mortalities, and the prevalence of severe manifestations of nutritional deficiencies, but the pace has been slow and falls short of national and Millennium Development Goal targets. The likely explanations include social inequities, disparities in health systems between and within states, and consequences of urbanisation and demographic transition. In 2005, India embarked on the National Rural Health Mission, an extraordinary effort to strengthen the health systems. However, coverage of priority interventions remains insufficient, and the content and quality of existing interventions are suboptimum. Substantial unmet need for contraception remains, adolescent pregnancies are common, and access to safe abortion is inadequate. Increases in the numbers of deliveries in institutions have not been matched by improvements in the quality of intrapartum and neonatal care. Infants and young children do not get the health care they need; access to effective treatment for neonatal illness, diarrhoea, and pneumonia shows little improvement; and the coverage of nutrition programmes is inadequate. Absence of well functioning health systems is indicated by the inadequacies related to planning, financing, human resources, infrastructure, supply systems, governance, information, and monitoring. We provide a case for transformation of health systems through effective stewardship, decentralised planning in districts, a reasoned approach to financing that affects demand for health care, a campaign to create awareness and change health and nutrition behaviour, and revision of programmes for child nutrition on the basis of evidence. This agenda needs political commitment of the highest order and the development of a people's movement.
21349441
Paediatric stroke: genetic insights into disease mechanisms and treatment targets.
In children, stroke is as common as brain tumour and causes substantial mortality and long-term morbidity, with recurrence in up to 20%. There are three sets of international clinical guidelines relating to childhood stroke; however, acute and preventive treatment recommendations are based on interventions effective in adults, rather than data regarding efficacy in children. A wide spectrum of risk factors underlies childhood stroke, and these risk factors vary from those encountered in adults. Specific disease mechanisms implicated in childhood arterial ischaemic stroke have received little attention, but an increased understanding of disease pathogenesis could lead to novel targeted treatment approaches. Here, we consider insights into the pathogenesis of childhood arterial ischaemic stroke and cerebral arteriopathy, provided by current knowledge of Mendelian diseases that are associated with an increased risk of these conditions. We give particular attention to aspects of vascular development, homoeostasis, and response to environmental effects. Our analysis highlights a potential role for interventions already licensed for pharmaceutical use, as well as new therapeutic targets and avenues for further research.
21371656
Seasonal influenza epidemiology in sub-Saharan Africa: a systematic review.
Acute respiratory infection (ARI) is a leading cause of mortality worldwide, of which influenza is an important cause that can be prevented with vaccination. We did a systematic review of research published from 1980 to 2009 on seasonal influenza epidemiology in sub-Saharan Africa to identify data strengths and weaknesses that might affect policy decisions, to assess the state of knowledge on influenza disease burden, and to ascertain unique features of influenza epidemiology in the region. We assessed 1203 papers, reviewed 104, and included 49 articles. 1-25% of outpatient ARI visits were caused by influenza (11 studies; mean 9*5%; median 10%), whereas 0*6-15*6% of children admitted to hospital for ARI had influenza identified (15 studies; mean 6*6%; median 6*3%). Influenza was highly seasonal in southern Africa. Other data were often absent, particularly direct measurement of influenza incidence rates for all ages, within different patient settings (outpatient, inpatient, community), and for all countries. Data from sub-Saharan Africa are insufficient to allow most countries to prioritise strategies for influenza prevention and control. Key data gaps include incidence and case-fatality ratios for all ages, the contribution of influenza towards admission of adults to hospital for ARI, representative seasonality data, economic burden, and the interaction of influenza with prevalent disorders in Africa, such as malaria, HIV, and malnutrition.
21435708
Viral pneumonia.
About 200 million cases of viral community-acquired pneumonia occur every year-100 million in children and 100 million in adults. Molecular diagnostic tests have greatly increased our understanding of the role of viruses in pneumonia, and findings indicate that the incidence of viral pneumonia has been underestimated. In children, respiratory syncytial virus, rhinovirus, human metapneumovirus, human bocavirus, and parainfluenza viruses are the agents identified most frequently in both developed and developing countries. Dual viral infections are common, and a third of children have evidence of viral-bacterial co-infection. In adults, viruses are the putative causative agents in a third of cases of community-acquired pneumonia, in particular influenza viruses, rhinoviruses, and coronaviruses. Bacteria continue to have a predominant role in adults with pneumonia. Presence of viral epidemics in the community, patient's age, speed of onset of illness, symptoms, biomarkers, radiographic changes, and response to treatment can help differentiate viral from bacterial pneumonia. However, no clinical algorithm exists that will distinguish clearly the cause of pneumonia. No clear consensus has been reached about whether patients with obvious viral community-acquired pneumonia need to be treated with antibiotics. Apart from neuraminidase inhibitors for pneumonia caused by influenza viruses, there is no clear role for use of specific antivirals to treat viral community-acquired pneumonia. Influenza vaccines are the only available specific preventive measures. Further studies are needed to better understand the cause and pathogenesis of community-acquired pneumonia. Furthermore, regional differences in cause of pneumonia should be investigated, in particular to obtain more data from developing countries.
20980517
A recombinant measles virus unable to antagonize STAT1 function cannot control inflammation and is attenuated in rhesus monkeys.
Measles remains a leading cause of death worldwide among children because it suppresses immune function. The measles virus (MV) P gene encodes three proteins (P, V, and C) that interfere with innate immunity, controlling STAT1, STAT2, mda5, and perhaps other key regulators of immune function. We identified here three residues in the shared domain of the P and V proteins-tyrosine 110, valine 112, and histidine 115-that function to retain STAT1 in the cytoplasm and inhibit interferon transcription. This information was used to generate a recombinant measles virus unable to antagonize STAT1 function (STAT1-blind MV) differing only in these three residues from a wild-type strain of well-defined virulence. This virus was used to assess the relevance of P and V interactions with STAT1 for virulence in primates. When a group of six rhesus monkeys (Macaca mulatta) was inoculated intranasally with STAT1-blind MV, viremia was short-lived, and the skin rash and other clinical signs observed with wild-type MV were absent. The STAT1-blind virus less efficiently controlled the inflammatory response, as measured by enhanced transcription of interleukin-6 and tumor necrosis factor alpha in peripheral blood mononuclear cells from infected hosts. Importantly, neutralizing antibody titers and MV-specific T-cell responses were equivalent in hosts infected with either virus. These findings indicate that efficient MV interactions with STAT1 are required to sustain virulence in a natural host by controlling the inflammatory response against the virus. They also suggest that selectively STAT1-blind MV may have utility as vectors for targeted oncolysis and vaccination.