Evidence-based pediatric asthma interventions and outcome measures in a healthy homes program: An integrative review

Objective: Asthma disproportionately impacts and has poorer outcomes in low-income, minority, and inner-city children. The home environment has a profound impact on a child's asthma. Home-based asthma visits have the potential to positively impact a child's asthma, especially in targeted populations. The purpose of this integrative review is 1.) to explore the effectiveness of home-based education and environmental measures and 2.) to explore specific indicators and tools to measure pediatric asthma control and program effectiveness. Data Sources: Medline, CINHAL, and Ovid databases were searched from 2010 to 2017 utilizing the keywords healthy homes AND asthma and home based interventions AND asthma. Study Selections: A total of 71 articles were retrieved of which 27 articles met the inclusion criteria of English language, human subjects, and the inclusion of pediatric populations. Three additional articles were hand-searched from previous references. In total, 30 articles were reviewed. A quality appraisal was conducted utilizing standardized appraisal tools. Results: Home-based asthma education and environmental interventions have proven to be effective. The programs reviewed varied in types of interventions, intensity and duration, the type of provider, length of follow-up, and outcome measures. Successful programs were patient-centered, included a home assessment and individualized education and interventions, and were collaborative. Multiple outcome indicators such as health care utilization, asthma control, missed days of school or productivity, asthma symptoms, and verification of environmental remediation have been utilized. Conclusion: Home-based asthma programs can be beneficial to children with poorly controlled asthma and have the potential to be cost-effective.     

Versicherungsrechtliche Medizin. Gewerbepathologie. (Gewerbliche Vergiftungen)

International Journal of Legal Medicine -     

Lumbosacral glioblastoma and leptomeningeal gliomatosis complicating the course of a cervicothoracic astrocytoma WHO grade II

CASE REPORT: The reported female patient underwent sub-total resection of an intra-medullary cervicothoracic astrocytoma classified as WHO grade II in 1984 at the age of 18 months and received local irradiation. In 1989, a local recurrence was diagnosed and a partial resection was performed. Sixteen years later, a small recurrent cervicothoracic tumour was found and spinal seeding to the equine nerve roots and the left cerebellar cortex was apparent on MRI. The patient was implanted with a ventriculoperitoneal shunt for a pseudo-tumour cerebri producing papilloedema, which eventually lead to amaurosis. After an extended biopsy, the invasive lumbosacral tumour was classified as glioblastoma multiforme. Two months later, the patient died after rapid progression of the caudal cranial nerve dysfunction. DISCUSSION AND CONCLUSION: Anaplastic progression and dissemination of spinal astrocytomas even two decades after initial diagnosis and treatment are rare. Therapies and diagnostic follow-up strategies are discussed.     

A pilot study of whole body hyperthermia and local irradiation for advanced non-small cell lung cancer confined to the thorax

Six patients with Stage III non-small cell lung cancer completed therapy which consisted of 4 whole body hyperthermia (WBH) treatments during the first 2 weeks of a 6 week course of radiotherapy (60 Gy). A radiant heat system was used to deliver the 41.8 degree C WBH. To reduce the danger of transverse myelitis, the spinal cord (and therefore part of the mediastinum and contralateral hilar region) was not irradiated during the first 2 weeks of radiotherapy and concurrent WBH. Subsequent treatments (weeks 3-6) included conventional irradiation to the primary tumor, mediastinal lymph nodes and spinal cord. Areas of gross disease responded to therapy in 5/6 patients. No radiation pneumonitis was observed. In 2/6 patients, relapse (after 10 months and 6 months, respectively) occurred with malignant pericardial effusions. The mediastinum in these patients was not an area of bulky disease involvement initially. To eliminate such WBH-radiation sanctuary zones, the protocol was modified to include greater combined WBH-radiation treatment. This is accomplished by having one WBH treatment "sandwiched" between 2 radiation fractions. The preclinical basis for the revised protocol is presented.     

Retinoids and spermatogenesis: lessons from mutant mice lacking the plasma retinol binding protein.

Using Rbp4-null mice as models, we have established for the first time the kinetics of the spermatogenetic alterations during vitamin A deficiency (VAD). Our data demonstrate that the VAD-induced testicular degeneration arises through the normal maturation of germ cells in a context of spermatogonia differentiation arrest. They indicate that retinoic acid (RA) appears dispensable for the transition of premeiotic to meiotic spermatocytes, meiosis, and spermiogenesis. They confirm that RA plays critical roles in controlling spermatogonia differentiation, spermatid adhesion to Sertoli cells, and spermiation, and suggest that the VAD-induced arrest of spermatogonia differentiation results from simultaneous blocks in RA-dependent events mediated by RA receptor gamma (RARgamma) in spermatogonia and by RARalpha in Sertoli cells. They also provide evidence that expression of major RA-metabolizing enzymes is increased in mouse Sertoli cells upon VAD and that vitamin A-deficient A spermatogonia differ from their RA-sufficient counterparts by the expression of the Stra8 gene.     

Neuronal Cell Death in Scrapie-Infected Mice Is Due to Apoptosis

Neuronal loss is a salient yet poorly understood feature in the pathology of transmissible spongiform encephalopathies (prion diseases). Cell culture experiments with neurotoxic prion protein fragments suggest that neuronal cell death in these diseases may be due to apoptosis. To test this hypothesis in vivo we used the in situ end-labeling (ISEL) technique and electron microscopy to study cell death in an experimental scrapie system in the mouse. ISEL, which relies on the incorporation of labeled nucleotides in fragmented DNA by terminal transferase, showed labeled nuclei in the brains and retinae of mice infected with the 79A strain of scrapie, whereas no labeling was observed in control animals. In the retina the highest numbers of labeled nuclei were found in the outer nuclear layer 120 days post infection followed by massive cell loss in this layer. In the brain, labeled nuclei were mainly found in the granular layer of the cerebellum of terminally ill mice. This corresponded to the presence of small dark nuclei with condensed and occasionally fragmented chromatin at the light and electron microscopical levels. Our results support the hypothesis that neuronal loss in spongiform encephalopathies is due to apoptosis. This may explain the almost complete absence of inflammatory response in prion diseases in the face of widespread neuronal cell death, and may also have therapeutic implications in the future.     

Toll-like receptor expression reveals CpG DNA as a unique microbial stimulus for plasmacytoid dendritic cells which synergizes with CD40 ligand to induce high amounts of IL-12

Human plasmacytoid dendritic cells (DC) (PDC, CD123+) and myeloid DC (MDC, CD11c+) may be able to discriminate between distinct classes of microbial molecules based on a different pattern of Toll-like receptor (TLR) expression. TLR1-TLR9 were examined in purified PDC and MDC. TLR9, which is critically involved in the recognition of CpG motifs in mice, was present in PDC but not in MDC. TLR4, which is required for the response to LPS, was selectively expressed on MDC. Consistent with TLR expression, PDC were susceptible to stimulation by CpG oligodeoxynucleotide (ODN) but not by LPS, while MDC responded to LPS but not to CpG ODN. In PDC, CpG ODN supported survival, activation (CD80, CD86, CD40, MHC class II), chemokine production (IL-8, IP-10) and maturation (CD83). CD40 ligand (CD40L) and CpG ODN synergized to activate PDC and to stimulate the production of IFN-alpha and IL-12 including bioactive IL-12 p70. Previous incubation of PDC with IL-3 decreased the amount of CpG-induced IFN-alpha and shifted the cytokine response in favor of IL-12. CpG ODN-activated PDC showed an increased ability to stimulate proliferation of naive allogeneic CD4 T cells, butTh1 polarization of developing T cells required simultaneous activation of PDC by CD40 ligation and CpG ODN. CpG ODN-stimulated PDC expressed CCR7, which mediates homing to lymph nodes. In conclusion, our studies reveal that IL-12 p70 production by PDC is under strict control of two signals, an adequate exogenous microbial stimulus such as CpG ODN, and CD40L provided endogenously by activated T cells. Thus, CpG ODN acts as an enhancer of T cell help, while T cell-controlled restriction to foreign antigens is maintained.