Ventriculo-Peritoneal Shunt Infections in Infants and Children

Objective: To determine the rate and the type of ventriculoperitoneal (VP) shunt infections in infants and children admitted to King Fahad Hofuf hospital of Al-Ahsaa area at the Eastern Province of Saudi Arabia.Methods: From mid 2003 to end of 2006; VP shunt infection episodes were reviewed. Once infection was suspected, a cerebrospinal fluid (CSF) sample was taken and empirical antibiotics were recommended. Once infection was confirmed, VP shunt was removed and external ventricular drainage (EVD) was inserted until CSF became sterile after which a new shunt was inserted.Results: 25.9% of patients with VP shunts had infections which represents 29.3% of the procedures. 40% of infected patients had recurrent episodes. 59.1% of infections occurred throughout the first two months following insertion. Single pathogen was isolated in each episode. Pseudomonas auerginosa represented 50% of isolated pathogens compared with 18.2% with Staphylococcus epidermidis.Conclusions: There is a high incidence of VP shunt infections in King Fahad Hofuf hospital when compared with other international centres. Gram negative organisms are the most common cause of the infection

Traumatic brain injury in pediatric age group; predictors of outcome in Pediatric Intensive Care Unit

Objective: To determine predictors for outcomes of traumatic brain injury (TBI) in infants and children younger than twelve years admitted to our pediatric intensive care units (PICU).Methods: This is a retrospective cohort study from 2004-5, done at the PICU of King Fahad Hofuf Hospital, Eastern Province, Saudi Arabia. One hundred and six patients with TBI; 65 boys and 41 girls ages 12 or under, with a mean age of 5.7 years, were included. Of them, 11.3% died (Deaths group), 11% survived with neurological deficits (ND-group), and 77% survived with no neurological deficits (NND-group). The potential predictors for death or neurological deficits were examined.Results: 83% of deaths had initial Glascow coma scale (GCS) of ≤ 4/15, 50% of ND had initial GCS ≤ 8 and 27% of NND had GCS < 12. The initial brain CT was abnormal in 92% of deaths and ND groups, but in only 37% of NND. Combined brain pathologies were found in 92% of deaths, 63% of ND and only in 5% of NND. Hypotension was seen in 67% of deaths, 17% ND and only in 1% of NND. Mechanical ventilation was required in all deaths and more than half of ND. Liver enzymes were high in 50% of deaths and 66% of ND but in only 20% of NND. Serum albumin was low in 33% of deaths, 42% of ND and only 1% NND.Conclusion: Glasgow coma score, brain CT findings, combined brain pathologies, hypotension, high liver enzymes and low serum albumin predict outcome after TBI in pediatric age group

Role of treadmill training versus suspension therapy on balance in children with Down syndrome

Background and purpose: Maintaining balance is a subordinate but necessary requirement for most human actions. Most Down syndrome (DS) children, who constitute a large portion in our country, continue to evidence deficits in balance, co-ordination, and gait throughout childhood and adulthood. So, it is essential to seek an ideal physical therapy program to help in solving such a widespread problem. The present study was conducted to compare between the effect of treadmill training and suspension therapy on balance in children with DS.Subjects and methods: Thirty children born with DS from both sexes ranging in age from eight to ten years old were assigned into two groups of equal number. Study group I received treadmill training in addition to a designed exercises therapy program and study group II received suspension therapy in addition to the same exercises program given to the study group I. Stability indices were evaluated via using Biodex instrument system before and after three months of treatment.Results: The results revealed no significant difference when comparing the pre-treatment mean values of the two groups (study I and study II), while significant improvement was observed in all the measuring variables of the two groups when comparing their pre and post treatment mean values. Significant difference was also observed when comparing the post treatment results of the two groups in favor of the study group II.Conclusion: Suspension therapy for children with DS is an excellent supplement to regularly scheduled physical therapy intervention for the purpose of improving the degree of stability in those patients.Keywords: Down syndrome; Balance; Treadmill; Suspension therap

Framework for Implementing a Supplier Kanban System through Action Research Methodology

Purpose: The aim of this study is to develop a framework for the implementation of a Supplier Kanban System Design/methodology/approach: The research was conducted within a factory focusing on the warehousing and supplier-related operations using an action research methodology Findings: The study period spanning over six years was aimed to reduce the inventory and the manpower required to manage this inventory. This initiative led to a substantial average savings of more than 500,000 Malaysian Ringgit annually Research limitations/implications: The focus of the study is on a framework for implementing a Supplier Kanban System in a small or medium-sized company within the automotive industry Practical implications: This framework is designed to be self-sufficient such that the members of the organisation can use it without the help of external experts or consultants Social implications: Reduction in inventory stored in the warehouse, the amount of redundant work carried out by the employees and other non-monetary improvements which are difficult to a monetise resulted in a much better work environment and happier employees Originality/value: The changing in the paradigm of the manufacturing value chain affects the tier 1 and tier 2 suppliers in Malaysia. The lines and value chains posing challenges to the suppliers have brought the idea of the Supplier Kanban system. The Supplier Kanban System adopted the Action Research Cycles and Continuous Learning Cycles, and this process was documented and developed as the Framework for the Implementation of a Supplier Kanban System

Soluble egg antigen of Schistosoma Haematobium induces HCV replication in PBMC from patients with chronic HCV infection

BACKGROUND: This study was conducted to examine, in vitro , the effect of soluble egg antigen (SEA) of S. haematobium on intracellular HCV RNA load in peripheral mononuclear cells (PBMC) as well as on cell proliferation in patients with chronic HCV infection. METHODS: PBMC from 26 patients with chronic HCV infection were cultured for 72 hours in presence and absence of 50 μg SEA/ml medium. Intracellular HCV RNA quantification of plus and minus strands was assessed before and after stimulation. PBMC from five healthy subjects were cultured for 7 days, flow cytometric analysis of DNA content was used to assess the mitogenic effect of SEA on PBMC proliferation compared to phytoheamaglutinine (PHA). RESULTS: Quantification of the intracellular viral load showed increased copy number/cell of both or either viral strands after induction with SEA in 18 of 26 patients (69.2%) thus indicating stimulation of viral replication. Flow cytometric analysis showed that mean ± S.D. of percent values of cell proliferation was induced from 3.2 ± 1.5% in un-stimulated cells to 16.7 ± 2.5 % and 16.84 ± 1.7 % in cells stimulated with PHA and SEA respectively. CONCLUSION: the present study supports earlier reports on SEA proliferative activity on PBMC and provides a strong evidence that the higher morbidity observed in patients co-infected with schistosomiasis and HCV is related, at least in part, to direct stimulation of viral replication by SEA

Innate Immune Response to Rift Valley Fever Virus in Goats

Rift Valley fever (RVF), a re-emerging mosquito-borne disease of ruminants and man, was endemic in Africa but spread to Saudi Arabia and Yemen, meaning it could spread even further. Little is known about innate and cell-mediated immunity to RVF virus (RVFV) in ruminants, which is knowledge required for adequate vaccine trials. We therefore studied these aspects in experimentally infected goats. We also compared RVFV grown in an insect cell-line and that grown in a mammalian cell-line for differences in the course of infection. Goats developed viremia one day post infection (DPI), which lasted three to four days and some goats had transient fever coinciding with peak viremia. Up to 4% of peripheral blood mononuclear cells (PBMCs) were positive for RVFV. Monocytes and dendritic cells in PBMCs declined possibly from being directly infected with virus as suggested by in vitro exposure. Infected goats produced serum IFN-γ, IL-12 and other proinflammatory cytokines but not IFN-α. Despite the lack of IFN-α, innate immunity via the IL-12 to IFN-γ circuit possibly contributed to early protection against RVFV since neutralising antibodies were detected after viremia had cleared. The course of infection with insect cell-derived RVFV (IN-RVFV) appeared to be different from mammalian cell-derived RVFV (MAM-RVFV), with the former attaining peak viremia faster, inducing fever and profoundly affecting specific immune cell subpopulations. This indicated possible differences in infections of ruminants acquired from mosquito bites relative to those due to contact with infectious material from other animals. These differences need to be considered when testing RVF vaccines in laboratory settings

Validation of the ALS Assay in Adult Patients with Culture Confirmed Pulmonary Tuberculosis

BACKGROUND: We have earlier shown that Bacille Calmette-Guérin (BCG) vaccine-specific IgG Antibodies in Lymphocyte Supernatant (ALS) can be used for diagnosis of active tuberculosis (TB) in adults and children. METHODOLOGY/PRINCIPAL FINDINGS: The ALS method was validated in a larger cohort (n = 212) of patients with suspicion of pulmonary TB using multiple antigens (BCG, LAM, TB15.3, TB51A, CFP10-ESAT6-A, CFP, CW) from Mycobacterium tuberculosis. The sensitivity and specificity of the ALS assay was calculated using non-TB patients as controls. The sensitivity and the specificity were highest with BCG vaccine (90% and 88% respectively) followed by LAM (89% and 87% respectively). Simultaneous assessment of multiple antigen-specific antibodies increased sensitivity (91%) and specificity (88%). Using higher lymphocyte count in smaller volume of culture media increased detection and reduced the assay duration to ∼30 hrs. Twenty one patients with clinical findings strongly suggestive of TB finally diagnosed as non-TB patients were positive by the ALS assay, of which 9 (43%) were positive for 7 antigens and 19 (90%) for at least 3 antigens. CONCLUSIONS/SIGNIFICANCE: Our findings show that simultaneous detection of antigens improves the diagnostic potential of the ALS assay; the modified method increases sensitivity and can provide results in <48 hours, and enable detection of some cases of pulmonary TB that are not detectable by standard methods

Phase I Evaluation of STA-1474, a Prodrug of the Novel HSP90 Inhibitor Ganetespib, in Dogs with Spontaneous Cancer

The novel water soluble compound STA-1474 is metabolized to ganetespib (formerly STA-9090), a potent HSP90 inhibitor previously shown to kill canine tumor cell lines in vitro and inhibit tumor growth in the setting of murine xenografts. The purpose of the following study was to extend these observations and investigate the safety and efficacy of STA-1474 in dogs with spontaneous tumors.This was a Phase 1 trial in which dogs with spontaneous tumors received STA-1474 under one of three different dosing schemes. Pharmacokinetics, toxicities, biomarker changes, and tumor responses were assessed. Twenty-five dogs with a variety of cancers were enrolled. Toxicities were primarily gastrointestinal in nature consisting of diarrhea, vomiting, inappetence and lethargy. Upregulation of HSP70 protein expression was noted in both tumor specimens and PBMCs within 7 hours following drug administration. Measurable objective responses were observed in dogs with malignant mast cell disease (n = 3), osteosarcoma (n = 1), melanoma (n = 1) and thyroid carcinoma (n = 1), for a response rate of 24% (6/25). Stable disease (>10 weeks) was seen in 3 dogs, for a resultant overall biological activity of 36% (9/25).This study provides evidence that STA-1474 exhibits biologic activity in a relevant large animal model of cancer. Given the similarities of canine and human cancers with respect to tumor biology and HSP90 activation, it is likely that STA-1474 and ganetespib will demonstrate comparable anti-cancer activity in human patients

Herpes Simplex Virus Dances with Amyloid Precursor Protein while Exiting the Cell

Herpes simplex type 1 (HSV1) replicates in epithelial cells and secondarily enters local sensory neuronal processes, traveling retrograde to the neuronal nucleus to enter latency. Upon reawakening newly synthesized viral particles travel anterograde back to the epithelial cells of the lip, causing the recurrent cold sore. HSV1 co-purifies with amyloid precursor protein (APP), a cellular transmembrane glycoprotein and receptor for anterograde transport machinery that when proteolyzed produces A-beta, the major component of senile plaques. Here we focus on transport inside epithelial cells of newly synthesized virus during its transit to the cell surface. We hypothesize that HSV1 recruits cellular APP during transport. We explore this with quantitative immuno-fluorescence, immuno-gold electron-microscopy and live cell confocal imaging. After synchronous infection most nascent VP26-GFP-labeled viral particles in the cytoplasm co-localize with APP (72.8+/−6.7%) and travel together with APP inside living cells (81.1+/−28.9%). This interaction has functional consequences: HSV1 infection decreases the average velocity of APP particles (from 1.1+/−0.2 to 0.3+/−0.1 µm/s) and results in APP mal-distribution in infected cells, while interplay with APP-particles increases the frequency (from 10% to 81% motile) and velocity (from 0.3+/−0.1 to 0.4+/−0.1 µm/s) of VP26-GFP transport. In cells infected with HSV1 lacking the viral Fc receptor, gE, an envelope glycoprotein also involved in viral axonal transport, APP-capsid interactions are preserved while the distribution and dynamics of dual-label particles differ from wild-type by both immuno-fluorescence and live imaging. Knock-down of APP with siRNA eliminates APP staining, confirming specificity. Our results indicate that most intracellular HSV1 particles undergo frequent dynamic interplay with APP in a manner that facilitates viral transport and interferes with normal APP transport and distribution. Such dynamic interactions between APP and HSV1 suggest a mechanistic basis for the observed clinical relationship between HSV1 seropositivity and risk of Alzheimer's disease