Scarlet fever outbreak in two nurseries in southwest England.
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Biomedical subjects
Publications and source records attributed to D Lewis.
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Levels of semicarbazide were determined by liquid chromatography-tandem mass spectrometry using isotope dilution ((13)C(15)N(2)-semicarbazide) methodology, and they were measured, after hydrolysis in 0.125 M hydrochloric acid and derivatization with 2-nitrobenzaldehyde, as a sum of free and bound semicarbazide. Levels of semicarbazide in 11 bakery products, which were sampled at three time intervals from the same source, varied from not detected (<1ng g(-1)) to 560 ng g(-1). In some instances, concentrations of semicarbazide varied between batches of the same product, at times more than tenfold, suggesting that the addition of azodicarbonamide to the same product is not standardized in many baking establishments.
Common complications associated with steroid therapy are well documented. We report a rare and fatal complication, in which oesophageal erosion secondary to the use of steroids was associated with pneumopericardium.
BACKGROUND: The solubility of dental pulp tissue in sodium hypochlorite has been extensively investigated but results have been inconsistent; due most likely to variations in experimental design, the volume and/or rate of replenishment of the solutions used and the nature of the tissues assessed. Traditionally, the sodium hypochlorite solutions used for endodontic irrigation in Australia have been either Milton or commercial bleach, with Milton being the most common. Recently, a range of Therapeutic Goods Administration (TGA) approved proprietary sodium hypochlorite solutions, which contain surfactant, has become available. Some domestic chlorine bleaches now also contain surfactants. The purpose of this study was to perform new solubility assessments, comparing Milton with new TGA approved products, Hypochlor 1% and Hypochlor 4% forte, and with a domestic bleach containing surfactant (White King). METHODS: Ten randomly assigned pulp samples of porcine dental pulp of approximately equal dimensions were immersed in the above solutions, as well as representative concentrations of sodium hydroxide. Time to complete dissolution was measured and assessed statistically. RESULTS: White King 4% showed the shortest dissolution time, closely followed by Hypochlor 4% forte. White King 1% and Hypochlor 1% each took around three times as long to completely dissolve the samples of pulp as their respective 4% concentrations, while Milton took nearly 10 times as long. The sodium hydroxide solutions showed no noticeable dissolution of the pulp samples. CONCLUSIONS: The composition and content of sodium hypochlorite solutions had a profound effect on the ability of these solutions to dissolve pulp tissue in vitro. Greater concentrations provided more rapid dissolution of tissue. One per cent solutions with added surfactant and which contained higher concentrations of sodium hydroxide were significantly more effective in dissolution of pulp tissue than Milton.
In August 2004 seven cases of Escherichia coli O157 infection were identified in children on holiday in Cornwall, southwest England, all of whom had stayed at different sites in the area. Isolates from all seven cases were confirmed as E. coli serogroup O157 phage type 21/28. We carried out a case-control study among holidaymakers who visited the beach. A standardised questionnaire was administered by telephone to parents. They were asked where on the beach the children had played, whether they had had contact with the stream that flowed across the beach, and about their use of food outlets and sources of food eaten. Cases were more likely to have played in the stream than controls (OR [1.72- undefined]). The time spent in the stream by cases was twice spent there by controls. Cases and controls were equally exposed to other suspected risk factors. PFGE profiles for all the cases were indistinguishable. Increased numbers of coliforms were found in the stream prior to the outbreak. Cattle were found grazing upstream. We suggest that the vehicle of infection for an outbreak of acute gastrointestinal illness caused by E. coli O157 was a contaminated freshwater stream flowing across a seaside beach. The onset dates were consistent with a point source. Heavy rainfall in the days preceding the outbreak might have lead to faeces from the cattle potentially contaminated by E. coli O157 contaminating the stream, thereby leading to the outbreak. Control measures included fencing off the part of the stream in which children played, and putting up warning signs around the beach.
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Pressure for acute hospital beds is a national problem with many acute trauma patients being admitted to non-trauma wards. This prospective multicentre questionnaire study of 220 qualified trauma and non-trauma nurses aims to compare the quality of nursing care that trauma patients receive when admitted to trauma wards and non-trauma wards. The questions included the nursing management of common fractures and post-operative conditions. The completed questionnaires were scored and the results analysed. Hundred percent of the questionnaires were completed and returned. The trauma nurses conveyed the importance of ice (85%) and elevation (97%) in the initial management of limb fractures. This compares with ice (10%) and elevation (50%) on the outlying wards. Trauma nurses correctly monitor for potentially devastating post-operative complications and compartment syndrome 87% of the time compared with 42% on outlying wards. Spinal injuries are managed appropriately 88% of the time on trauma wards compared with 36% on outlying wards. Trauma patients receive better nursing care when admitted to a trauma ward and are nursed by trauma nurses. Many of the out-lying wards provide sub-optimal trauma nursing care and a few are positively dangerous. We suggest that trauma patients should not be nursed on outlying wards.
OBJECTIVES: To describe the clinical and immunologic characteristics of human immunodeficiency virus type-1 (HIV-1)-infected children surviving to more than eight-years of age (long-survivors) before the introduction of antiretroviral therapy. METHODS: This report is based on all the long-term survivors from a prospective cohort of HIV-infected children born to HIV-positive women in Barbados during 1986-1995. Infants born to HIV-infected women were enrolled into this cohort at birth or at the time of diagnosis of HIV exposure in the postnatal period and followed-up at regular intervals. RESULTS: From a cohort of 44 HIV-infected children, 17 (38.6%) children survived to the age of eight years and beyond and were classified as long-term survivors. Median age of the sixteen long-term surviving children alive at the time of this report was 12 years (age range 8 - 16.7 years). At the age of 8 years, 17.6% of these children remained asymptomatic. Nine (52.9%) children had no immunodeficiency (CD4 counts >500 cells x 10(6)/L). Of the 16 long-term surviving children who were alive and had a median follow-up of 4.1 years (range 0.1 year to 8.5 years) after their eighth birthday, 37.5% had a CD4 cell count greater than 500 cells x 10(6)/L and had either no symptoms or only mild symptoms of HIV infection and were therefore categorized as the long-term non-progressors. CONCLUSIONS: In a small cohort of HIV-infected children, in the absence of antiretroviral therapy, only about one-third survived beyond eight years of age. On further follow-up of these long-term surviving children, over one-third had a slow rate of disease progression.
OBJECTIVE: To review evidence on the pharmacologic treatment of the child with migraine headache. METHODS: The authors reviewed, abstracted, and classified relevant literature. Recommendations were based on a four-tiered scheme of evidence classification. Treatment options were separated into medications for acute headache and preventive medications. RESULTS: The authors identified and reviewed 166 articles. For acute treatment, five agents were reviewed. Sumatriptan nasal spray and ibuprofen are effective and are well tolerated vs placebo. Acetaminophen is probably effective and is well tolerated vs placebo. Rizatriptan and zolmitriptan were safe and well tolerated but were not superior to placebo. For preventive therapy, 12 agents were evaluated. Flunarizine is probably effective. The data concerning cyproheptadine, amitriptyline, divalproex sodium, topiramate, and levetiracetam were insufficient. Conflicting data were found concerning propranolol and trazodone. Pizotifen, nimodipine, and clonidine did not show efficacy. CONCLUSIONS: For children (>age 6 years), ibuprofen is effective and acetaminophen is probably effective and either can be considered for the acute treatment of migraine. For adolescents (>12 years of age), sumatriptan nasal spray is effective and should be considered for the acute treatment of migraine. For preventive therapy, flunarizine is probably effective and can be considered, but is not available in the United States. There are conflicting or insufficient data to make any other recommendations for the preventive therapy of migraine in children and adolescents. For a clinical problem so prevalent in children and adolescents, there is a disappointing lack of evidence from controlled, randomized, and masked trials.
Transient elevations of cytosolic Ca2+ are a common mechanism of cellular signaling. In striated muscle, the sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA) plays an important role in terminating Ca2+ transients by returning cytosolic Ca2+ to intracellular stores. Stored Ca2+ can then be released again for subsequent signaling. We down-regulated SERCA2 gene expression in cultured cardiac myocytes by means of endogenous transcription of small interfering RNA encoded by an exogenous cDNA template. The cDNA template was delivered by adenovirus vector. Reduction of SERCA expression in all myocytes in culture was documented by immunochemistry, real-time RT-PCR, and determination of ATP-dependent Ca2+ transport. The reduction of SERCA2 expression was associated with the up-regulation of transient receptor potential (TRP) channel proteins (TRPC4 and TRPC5) and Na+/Ca2+ exchanger, indicating that intracellular store deficiency was compensated for by Ca2+ fluxes through the plasma membrane. In fact, SERCA silencing was followed by increased transcription of Na+/Ca2+ exchanger, TRPC4, TRPC5, and related transcriptional factors, such as stimulating protein 1, myocyte enhancer factor 2, and nuclear factor of activated cells 4, through activation of calcineurin. This finding demonstrates that the observed compensation occurs through transcriptional crosstalk and the remodeling of Ca2+ signaling pathways. The wide significance of this regulatory mechanism is related to its general involvement in Ca2+ signaling dynamics and in cardiac development and hypertrophy.
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OBJECTIVE: To test the hypothesis that a delay in initial fetal cell enrichment processing of maternal blood samples (defined as the time between blood draw and the initial density gradient centrifugation step) compromises the ability to recover fetal cells, we performed a randomized comparison of immediate (within 4 hours of draw) versus delayed (between 18-24 hours of draw) processing. METHODS: Four centers participated: two centers utilized flow cytometry (FLOW), and two centers utilized magnetic-activated cell sorting (MACS) techniques. Each center collected 34 samples. The outcome was the percentage of gamma positive (gamma(+)) cells for FLOW or the number of nucleated red blood cells (NRBCs) for MACS, found in the final enriched cell population. Both outcomes reflect cell properties that are potentially fetal in origin, thus making them representative of the ability to recover fetal cells. RESULTS: Our results did not support our hypothesis that delay in processing compromises fetal cell recovery. Instead, in MACS processing, we observed an increase in recovered NRBCs when blood sample processing was delayed compared with immediate processing. There was no significant difference in gamma(+) cells with FLOW. CONCLUSION: Time-related changes in the density of target cells, perhaps associated with their progress towards apoptosis during the delay period, may result in increased intact fetal cells with the study methods utilized.
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Although dry powder inhalers are well established for the delivery of corticosteroids, the pressurised metered dose inhaler remains the preferred and most cost effective presentation. To design an HFA solution formulation which matched marketed CFC products (Pulmicort and Desonac DA) two elements of the Chiesi Modulite system, the addition of a non-volatile component and the actuator orifice diameter, were varied. These variables, which were shown by in vitro tests to influence the fine particle dose and its mean particle size in different ways, could be permuted to give an aerosol cloud with size characteristics very close to the comparator products. The likelihood that this would confer clinical equivalence is reinforced by a pharmacokinetic analysis which showed that the chosen HFA solution formula gave similar systemic absorption from the lung as Pulmicort. The equivalence in aerosol characteristics was sustained when the pressurised metered dose inhalers (pMDIs) were used with spacers. The Chiesi Jet and the AstraZeneca Nebuhaler, when used with their respective pMDIs, reduced likely oropharyngeal deposition to the same extent and gave a similar increase in the fine particle dose.
Isolation and analysis of intact fetal cells in maternal blood is an attractive method of non-invasive prenatal diagnosis; however, detection levels are not optimal. The poor sensitivity and inconsistent recovery of fetal cells is compounded by small numbers of circulating fetal cells and loss of fetal cells during enrichment procedures. Optimizing selection criteria by utilizing less complicated methods for target cell enrichment is essential. We report here salutary results using a simple density-based depletion method that requires neither MACS (magnetic-activated cell sorting) nor flow cytometric separation for enrichment of progenitor cells. Maternal blood samples (n = 81) were obtained from women prior to invasive prenatal genetic diagnostic procedures and processed randomly within 24 h using one of two density-based enrichment methods. For progenitor cell enrichment, samples (n = 49) were labeled with a RosetteSep progenitor antibody cocktail to remove unwanted mature T-cells, B-cells, granulocytes, natural killer cells, neutrophils and myelomonocytic cells. For CD45-negative cell enrichment, samples (n = 14) were labeled with RosetteSep CD45 antibody to remove unwanted maternal white cells. The desired cellular fraction was collected and analyzed by either fluorescent in situ hybridization (FISH) or real-time PCR for the presence of intact fetal cells and to quantify Y-chromosome-specific DYS1 sequences, respectively. Overall, FISH and real-time PCR correct detection rates for the progenitor cell enrichment approach were 53% and 89% with 3% (1 out of 30 cases) and 0% false-positive detection, respectively. Fetal sequences were detected in the range from 0.067 to 1.167 genome equivalents per milliliter of blood. No fetal cells were detected using the CD45-negative enrichment method. Flow cytometric analysis of cord blood showed that a unique myeloid population of cells was recovered using RosetteSep trade mark progenitor enrichment compared with the CD45-negative enrichment method. Sensitivity of the RosetteSep progenitor enrichment approach for detection of fetal cells in this pilot study shows great promise with recovery of cells that are suitable for FISH and automated microscope scanning. This simple and rapid method may also allow expansion in culture and characterization of the fetal cell type(s) that circulate in maternal blood, hence, greatly improving reliability of non-invasive prenatal diagnosis.
BACKGROUND AND OBJECTIVE: Alexander disease is a slowly progressive CNS disorder that most commonly occurs in children. Until recently, the diagnosis could only be established by the histologic finding of Rosenthal fibers in brain specimens. Mutations in the glial fibrillary acidic protein (GFAP) gene have now been shown in a number of biopsy- or autopsy-proven patients with Alexander disease. A prospective study on patients suspected to have Alexander disease was conducted to determine the extent to which clinical and MRI criteria could accurately diagnose affected individuals, using GFAP gene sequencing as the confirmatory assay. METHODS: Patients who showed MRI white matter abnormalities consistent with Alexander disease, unremarkable family history, normal karyotype, and normal metabolic screening were included in this study. Genomic DNA from patients was screened for mutations in the entire coding region, including the exon-intron boundaries, of the GFAP gene. RESULTS: Twelve of 13 patients (approximately 90%) were found to have mutations in GFAP. Seven of those 12 patients presented in infancy with seizures and megalencephaly. Five were juvenile-onset patients with more variable symptoms. Two patients in the latter group were asymptomatic or minimally affected at the time of their initial MRI scan. The mutations were distributed throughout the gene, and all involved sporadic single amino acid heterozygous changes that changed the charge of the mutant protein. Four of the nine changes were novel mutations. CONCLUSIONS: In symptomatic and asymptomatic patients with a predominantly frontal leukoencephalopathy by MRI, GFAP gene mutation analysis should be included in the initial diagnostic evaluation process for Alexander disease.
OBJECTIVES: The National Institute of Child Health and Human Development Fetal Cell Isolation Study (NIFTY) is a prospective, multicenter clinical project to develop non-invasive methods of prenatal diagnosis. The initial objective was to assess the utility of fetal cells in the peripheral blood of pregnant women to diagnose or screen for fetal chromosome abnormalities. METHODS: Results of fluorescence in situ hybridization (FISH) analysis on interphase nuclei of fetal cells recovered from maternal blood were compared to metaphase karyotypes of fetal cells obtained by amniocentesis or chorionic villus sampling (CVS). After the first 5 years of the study we performed a planned analysis of the data. We report here the data from 2744 fully processed pre-procedural blood samples; 1292 samples were from women carrying singleton male fetuses. RESULTS: Target cell recovery and fetal cell detection were better using magnetic-based separation systems (MACS) than with flow-sorting (FACS). Blinded FISH assessment of samples from women carrying singleton male fetuses found at least one cell with an X and Y signal in 41.4% of cases (95% CI: 37.4%, 45.5%). The false-positive rate of gender detection was 11.1% (95% CI: 6.1,16.1%). This was higher than expected due to the use of indirectly labeled FISH probes in one center. The detection rate of finding at least one aneuploid cell in cases of fetal aneuploidy was 74.4% (95% CI: 76.0%, 99.0%), with a false-positive rate estimated to be between 0.6% and 4.1%. CONCLUSIONS: The sensitivity of aneuploidy detection using fetal cell analysis from maternal blood is comparable to single marker prenatal serum screening, but technological advances are needed before fetal cell analysis has clinical application as part of a multiple marker method for non-invasive prenatal screening. The limitations of the present study, i.e. multiple processing protocols, are being addressed in the ongoing study.
Simultaneous infection of a plant by two viruses can cause more severe disease than is caused by infection with either virus alone. Such synergy may be due to effects on the replication of one virus by the second virus or to other causes. The tobamovirus turnip vein-clearing virus (TVCV), itself causing almost imperceptible symptoms in infected turnips, exacerbated symptoms of infection of turnip by the Cabbage S isolate of the caulimovirus cauliflower mosaic virus (CaMV). The synergy in symptom production was most evident in a reduced size of leaves, providing an objective measure of synergy. In contrast, synergy did not occur when the CM4-184 isolate of CaMV was used in combination with TVCV. Both isolates of CaMV increased the level of TVCV accumulated in leaves. TVCV did not increase the level of the Cabbage S CaMV isolate. The use of Cabbage S-CM4-184 chimeras revealed that a region critical for isolate synergy in stunting was within the coat protein gene and/or the 5' one third of the reverse transcriptase gene. We conclude that the disease symptom synergy between TVCV and Cabbage S CaMV is not caused by altered levels of accumulation of the viruses, but instead reflects subtle genetic interactions mapping to the ORF IV-ORF V region of CaMV DNA.