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Oral oseltamivir improves pulmonary function and reduces exacerbation frequency for influenza-infected children with asthma.

BACKGROUND: Among asthmatic children, influenza is associated with increased hospitalizations. Although vaccination is safe and effective among asthmatic children, its protective efficacy varies and uptake rates can be low. In comparison, oseltamivir (Tamiflu) is effective against all influenza strains and can reduce the severity and duration of influenza among adults and children. This study determined the effects of oseltamivir among influenza-infected children with asthma. METHODS: Asthmatic children (6-12 years of age) were randomized to receive oseltamivir (2 mg/kg) or placebo twice daily, as a syrup. The primary efficacy endpoint was the time to freedom from illness. Secondary endpoints included the area under the symptom score-hour curve, the proportion of patients with asthma exacerbations and changes in forced expiratory volume at 1 second during the dosing period. Analysis was performed for both the intent-to-treat infected (n = 179) and per protocol (n = 162) populations. RESULTS: The primary endpoint for this study was not met. Oseltamivir tended to reduce the time to freedom from illness in the intent-to-treat infected population (10.4 hours, 8%; P = 0.5420), the per protocol population (24.3 hours, 17%; P = 0.1607) and patients who started treatment <24 hours after symptom onset (39.8 hours, 25%; P = 0.0780). However, an improvement in pulmonary function was observed. The improvement in forced expiratory volume at 1 second was significantly greater among oseltamivir-treated patients (10.8% versus 4.7%; P = 0.0148). Oseltamivir-treated patients also experienced fewer asthma exacerbations up to day 7 (68% versus 51%; P = 0.031). Oseltamivir was safe and well-tolerated. CONCLUSIONS: Oseltamivir is safe and well-tolerated among asthmatic children, may reduce symptom duration and helps improve lung function and reduce asthma exacerbations during influenza infection.

Acetamides↗

Brain incorporation of [11C]arachidonic acid in young healthy humans measured with positron emission tomography.

Arachidonic acid (AA) is an important second messenger involved in signal transduction mediated by phospholipase A2. The goal of this study was to establish an in vivo quantitative method to examine the role of AA in this signaling process in the human brain. A simple irreversible uptake model was derived from rat studies and modified for positron emission tomography (PET) to quantify the incorporation rate K* of [11C]AA into brain. Dynamic 60-minute three-dimensional scans and arterial input functions were acquired in 8 young healthy adults studied at rest. Brain radioactivity was corrected for uptake of the metabolite [11C]CO2. K* and cerebral blood volume (Vb) were estimated pixel-by-pixel and were calculated in regions of interest. K* equaled 5.6+/-1.2 and 2.6+/-0.5 microL x min(-1) x mL(-1) in gray and white matter, respectively. K* and Vb values were found to be unchanged with data analysis periods from 20 to 60 minutes. Thus, PET can be used to obtain quantitative images of the incorporation rate K* of [11C]AA in the human brain. As brain incorporation of labeled AA has been shown in awake rats to be increased by pharmacological activation associated with phospholipase A2-signaling, PET and [11C]AA may be useful to measure signal transduction in the human brain.

Adult↗

Oligodendroglial-derived stress signals recruit microglia in vitro.

Rat oligodendrocytes cultured without the essential survival factors serum and insulin die over a 48 h period. Analysis of supernatants from these dying cultures reveals a microglial chemokine released in advance of significant cell death. The observed microglial chemotactic effect is dose-dependent and not due to release of cellular debris. Interferon (IFN)-gamma activated microglia are more sensitive to the microglial chemokine. We show in co-culture that recruited non-activated microglia can enhance oligodendroglial survival whereas IFN-gamma activation of microglia induces contact-dependent oligodendroglial death. Thus, whilst the initial recruitment of microglia by stressed oligodendroglia may represent part of a survival process engaged by injured cells, this does not necessarily ensure survival.

Animals↗

Impact of syphilis infection on HIV viral load and CD4 cell counts in HIV-infected patients.

OBJECTIVES: To assess the effect of early syphilis on HIV viral load (VL) and CD4 cell count in patients with HIV and to analyze factors associated with changes in HIV VL and CD4 cell count. DESIGN: Multicenter study of a series of patients with HIV who were diagnosed with early syphilis infection during 2004 through 2005. Patients who started or changed their highly active antiretroviral therapy (HAART) regimen during the analysis period were excluded. RESULTS: One hundred eighteen patients were analyzed: 95.8% were men, mean patient age was 38.2 years, 83.9% were homosexual men, 50.8% were on antiretroviral therapy at the time syphilis was diagnosed, and HIV and syphilis diagnoses were coincident in 38 (32.2%) cases. CD4 cell counts were lower during syphilis than before (590 vs. 496 cells/microL; P = 0.0001) and after syphilis treatment (509 vs. 597 cells/microL; P = 0.0001). The HIV VL increased in 27.6% of patients during syphilis. The only factor associated with an HIV VL increase was not being on HAART, and the only factor associated with a CD4 count decrease >100 cells/microL during syphilis was the prior CD4 cell count. CONCLUSIONS: Syphilis infection was associated with a decrease in the CD4 cell count and an increase in the HIV VL in almost one third of the patients. In this series, more than two thirds of the syphilis cases were diagnosed in patients who were previously known to be infected with HIV.

Adult↗

Effects of Heat Shock on Growth and on Lipid and beta-Glucan Synthetases in Leaves of Phaseolus vulgaris and Vigna sinensis.

Primary leaves of intact plants of Phaseolus vulgaris and Vigna sinensis 7 to 9 days old were dipped in water for 2 minutes at 47.4 +/- 0.2 C and 48.7 +/- 0.5 C, respectively. Leaf growth was inhibited within the first 20 hours, and growth partially or completely recovered in a subsequent 20-hour period. Analysis of the glucolipid and beta-1, 3- and beta-1, 4-glucan synthetases showed that the most evident effects of heat shock were the severe inhibition of the synthesis of beta-1, 4-glucosyl glycosidic linkages and stimulation of beta-1, 3-linkage synthesis. The stimulation appeared either immediately after treatment or within the first 20 hours and lasted at least 60 hours after treatment. Phaseolus plants reacted more intensely to the heat shock, reflecting a possible genetic difference in the response mechanisms.

Journal Article↗

Developmental Regulation of (1-->3, 1-->4)-beta-Glucanase Gene Expression in Barley : Tissue-Specific Expression of Individual Isoenzymes.

Two genes encode (1-->3,1-->4)-beta-d-glucan 4-glucanohydrolase (EC 3.2.1.73) isoenzymes EI and EII in barley (Hordeum vulgare L.). Specific DNA probes have been used in Northern analyses to examine the developmental regulation of individual (1-->3,1-->4)-beta-glucanase genes in the aleurone and scutellum of germinated grain and in young leaves and young roots. In aleurone and scutella excised from germinated grain, mRNAs encoding both isoenzymes are present but developmental patterns differ between the two tissues. Thus, levels of both isoenzyme EI and EII mRNA increase significantly in the aleurone between 1 and 3 days after the initiation of germination. In the scutellum, isoenzyme EI mRNA predominates and decreases as germination proceeds. Isoenzyme EI mRNA appears in young leaves approximately 8 days after the initiation of germination and levels rise until about 20 days. Enzyme activity in leaf extracts parallels the development of isoenzyme EI mRNA. No isoenzyme EII mRNA is detected in the leaves in this period. Analysis of RNA from different leaf segments indicates that the isoenzyme EI mRNA is distributed relatively evenly along the length of the leaf. In young roots, mRNA encoding (1-->3,1-->4)-beta-glucanase isoenzyme EI is detected at high levels 3 to 6 days after the initiation of germination; again, little or no isoenzyme EII mRNA is found. Overall, transcription of the (1-->3,1-->4)-beta-glucanase isoenzyme EII gene appears to be restricted to the germinating grain, whereas isoenzyme EI is expressed in a wider range of tissues during seedling development.

Journal Article↗

A straightforward frequency-estimation technique for GPS carrier-phase time transfer.

Although Global Positioning System (GPS) carrier-phase time transfer (GPSCPTT) offers frequency stability approaching 10-15 at averaging times of 1 d, a discontinuity occurs in the time-transfer estimates between the end of one processing batch (1-3 d in length) and the beginning of the next. The average frequency over a multiday analysis period often has been computed by first estimating and removing these discontinuities, i.e., through concatenation. We present a new frequency-estimation technique in which frequencies are computed from the individual batches then averaged to obtain the mean frequency for a multiday period. This allows the frequency to be computed without the uncertainty associated with the removal of the discontinuities and requires fewer computational resources. The new technique was tested by comparing the fractional frequency-difference values it yields to those obtained using a GPSCPTT concatenation method and those obtained using two-way satellite time-and-frequency transfer (TWSTFT). The clocks studied were located in Braunschweig, Germany, and in Boulder, CO. The frequencies obtained from the GPSCPTT measurements using either method agreed with those obtained from TWSTFT at several parts in 1016. The frequency values obtained from the GPSCPTT data by use of the new method agreed with those obtained using the concatenation technique at 1-4 x 10(-16).

Journal Article↗

Hypoxia in sleeping children: overnight studies can be reduced to 4 hours without loss of clinical significance.

Twelve recordings of overnight pulse oximetry representing a range of severity of obstructive sleep disturbance were evaluated by 7 experienced clinicians. Each recording was then scored by counting the number of minutes in each hour affected at any time by a fall in saturation to below 90%. Comparison of the clinical evaluation and the overall scores gave a clear level of 5 minutes per hour at and above which all the assessors agreed that the charts had clinically important desaturation. Overnight pulse oximetry was then performed on 25 children aged between 12 months and 10 years about to undergo adenotonsillectomy. The charts were scored by the method above with a score of 5 or more indicating a positive result for hypoxic episodes. The scores for shortened analysis periods of 1, 2, 3 and 4 hours duration were compared with the overall score and no cases which were negative, up to and including 4 hours, became positive in the overall result. Thus recording pulse oximetry for 4 hours provides sufficiently accurate information for clinical purposes.

Child↗

Degradation of the Poliovirus 1 genome by chlorine dioxide.

AIMS: This study was undertaken to gain an understanding of the factors that influence viral RNA degradation in the presence of chlorine dioxide (ClO(2)), which will be very useful in helping to define the significance of the presence of the viral genome in disinfected water. METHODS AND RESULTS: We focused our investigation on the influence of ClO(2) on extracted RNA on the one hand, and on the infectious virus on the other. Our first results show that RNA degradation, like viral inactivation, is dose dependent. The influence of the spatial organization of the targeted genomic sequence, as well as that of its size and location (and/or sequence) on degradation of the Poliovirus 1 genome by ClO(2), was studied using real-time reverse transcriptase-polymerase chain reaction (RT-PCR). The results show that the preferential sites of action of ClO(2) appear to be located in the untranslated regions, 5'- and 3'-UTR, a phenomenon influenced by both the presence of secondary structures and the genomic sequence in these regions. Our results also reveal a rapid decrease of infectious particles quantified by the cell culture for the applied dose. Comparison between cell culture and real-time PCR for viral detection reveals disagreement following disinfection treatment, even for the largest targeted fragment (a 6,989-base fragment representing the quasi-whole viral genome). CONCLUSIONS: The detection of genome fragments is insufficient to confirm the presence of the infectious virus, as each targeted fragment shows a different sensitivity. Hence, the smallest targeted fragment (76 bp) persisted throughout the analysis period, while the longest targeted fragment (6,989 bp) disappeared very rapidly. Highly sensitive regions (i.e. 5'- and 3'-UTR) should be targeted to avoid an overestimation of the risk of viral infection using molecular biology methods in water following disinfection. Further studies in this area are needed. SIGNIFICANCE AND IMPACT OF THE STUDY: To date, it has not been possible to routinely apply virological controls to drinking water because of the time-consuming nature of the gold standard technique (cell culture) and its inability to detect all serotypes (e.g. Norovirus). Molecular techniques (e.g. real-time RT-PCR) constitute a solution to the rapid and specific detection of all the serotypes. However, ignorance of the mechanisms of viral degradation prevents the validation of PCR for the measurement of the risk of infection to humans following disinfection treatment.

Chlorine Compounds↗

Interpreting trends in cancer patient survival.

Data on cancer patient survival are an invaluable tool in the evaluation of therapeutic progress against cancer as well as other lethal diseases. As with all quantitative information routinely used in evidence-based clinical management--including diagnostic tests, prognostic markers and comparisons of therapeutic interventions--data on patient survival require evaluation based on an understanding of the underlying statistical methodology, methods of data collection and classification, and, most notably, clinical and biologic insight. This article contains an introduction to the methods used for estimating cancer patient survival, including cause-specific survival, relative survival and period analysis. The methods, and their interpretation, are illustrated through presentation of trends in incidence, mortality and patient survival for a range of different cancers. Our aim was to lay out the strengths and limitations of survival analysis as a tool in the evaluation of progress in the diagnosis and treatment of cancer.

Data Collection↗

Government statistics of certified causes of perinatal mortality in Moscow and certain problems with its improvement.

While preparing the Ninth Revision of the International Classification of Diseases, Injuries and Causes of Death (1970-1975), the World Health Organisation sought ways of improving the accuracy of statistics of perinatal mortality. A new Certificate of Cause of Perinatal Death, developed for use in all regions of the USSR and introduced there in 1974, was recommended for introduction in other countries. This was based on the reorganised and more clear-cut coding outlined in Chapter XV of ICD-9. Comparison of the perinatal death rates in 1975 with those in 1986 showed a fall from 25 to 20 per 1000 births, with changes in causes related to changes on classification. Cross-tabulation of multiple-cause perinatal death was made possible by coding maternal conditions affecting the fetus or newborn separately from fetal conditions originating in the perinatal period. Analysis of the results of tabulation of multiple-cause perinatal death in Moscow in 1986 proceeded to a proposed structure for a Basic Tabulation List allowing comparisons of the statistics of perinatal mortality.

Cause of Death↗

Haematological effects of postoperative autotransfusion in spinal surgery.

A prospective, randomized, controlled study was performed to determine the haematological and biochemical changes and clinical safety of postoperative autotransfusion (Solcotrans Orthopedic Plus system) in patients undergoing spinal surgery. Fifty patients were studied and were randomly allocated to Control (n = 25) and Solcotrans (n = 25) groups. Both groups had their postoperatively drained blood collected into the Solcotrans reservoir but only the Solcotrans group had this salvaged blood considered for reinfusion. After a 5-h postoperative collection period, analysis of the shed blood showed a haematocrit of 0.26 +/- 0.11, few platelets (80 +/- 63 10g.l-1), a fibrinogen level of less than 0.1 g.l-1 and a high level of D-dimers. The salvaged blood did not clot and aerobic and anaerobic culture produced no growth. The volume of blood collected was greater than 200 ml in 21 patients in the Solcotrans group who were autotransfused (384 +/- 101 ml, range 200-600 ml), and in 16 patients in the Control group. Within 15 min following completion of reinfusion of the salvaged blood there was a significant, but moderate decrease in platelet count (181 +/- 74 vs 223 +/- 90 10g.l-1, P < 0.001) and fibrinogen concentrations (2.1 +/- 0.8 vs 2.3 +/- 0.9 g.l-1, P < 0.02), and an increase in circulating D-dimers (P < 0.001) and plasma free haemoglobin concentrations (236 +/- 155 vs 82 +/- 79 mg.l-1, P < 0.001). Prothrombin time (PT) and activated partial thromboplastin time (APTT) did not increase, and potassium concentrations were not significantly affected.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood↗

Somatic antigen of Shigella dysenteriae type 3. Structural features of specific polysaccharide chain.

On mild acid hydrolysis of lipolysaccharide from Shigella dysenteriae type 3 the O-specific polysaccharide (hapten) was obtained which appeared to be acidic branched hexosaminoglycan. The repeating unit of this polysaccharide represents a pentasaccharide composed of two D-galactose residues, N-acetyl-D-galactosamine, D-glucose and unidentified acidic component. On the basis of methylation analysis, periodate oxidation, partial acid hydrolysis and chromic anhydride oxidation it is concluded that the structure of the chemical repeating unit of polysaccharide is (see article) where Glcp is glucopyranose, Galp is galactopyranose, Galf is galactofuranose, GalNAcp is 2-acetamido-2-deoxygalactopyranose and where the configuration of galactofuranoside glycosidic linkage and the structure of the acidic monosaccharide A are not known.

Aluminum↗

Structural studies on Shigella flexneri serotype 6 core region.

The core structure of Shigella flexneri serotype 6 has been investigated. The methods used in these studies involved methylation analysis, periodate oxidation, Smith degradation and enzymic modifications of core oligosaccharides isolated from two smooth strains and four rough mutants. As a result the complete core region was established (Formula: see text) where DGalp = D-galactopyranose, DGlcp = D-glucopyranose, L alpha DHepp = L-glycero-D-mannoheptapyranose, dOclA = 3-deoxy-D-manno-octulosonic, DGlcNp = 2-amino-2-deoxy-D-glucopyranose and P--PEtN = pyrophosphorylethanolamine (partially substituted). In the R mutants examined two types of mutation have been observed: (1) defect in heptose region (lack of D-glucosamine) or (2) defects in hexose region of the core.

Carbohydrate Sequence↗

Structural studies on the capsular polysaccharide of Klebsiella serotype K40.

The capsular polysaccharide of Klebsiella serotype K40 contained D-mannose, D-glucuronic acid, D-galactose, and L-rhamnose in the approximate molar ratios 1:1:1:2. The primary structure of the capsular polysaccharide has been investigated mainly by methylation analysis, periodate oxidation, characterization of oligosaccharides, base degradation reaction, and 1H and 13CNMR spectroscopy. The polysaccharide does not contain any pyruvic acetal or O-acetyl substitution. It has a pentasaccharide repeating unit of the following primary structure: alpha-D-Manp 1----4 ----4)-beta-D-GlcpA-(1----2)-alpha-L-Rhap-(1----3)-beta-D-Ga lp-(1----2)-alpha- L-Rhap-(1----.

Carbohydrate Conformation↗

Primary, return and onward migration in the U.S. and Canada: is there a difference?

"Using microdata sources available from the U.S. Census Bureau and Statistics Canada, this paper contrasts primary, return and onward migration in the two countries. These classifications are based on information on the region (state or province) of birth and region of residence at the start and end of the census period. To study the propensities to make a primary, return or onward migration, rates are calculated...and compared with previous census periods. Analysis reveals that both countries have experienced similar temporal patterns, and that primary, return and onward migration patterns tend to be similar. Analysis using a nested logit model further reveals that return and onward migration in both countries can be similarly explained." Data are from the Public Use Micro Sample (PUMS) for the United States and the Public Use Micro File (PUMF) for Canada.

Americas↗

Frequency-volume charts: comparison of frequency between elderly and adult patients.

Urinary frequency is a common complaint in the elderly and can be due to many different causes. To clarify the aetiology of frequency, patient-maintained frequency-volume charts were evaluated as a diagnostic tool. We studied 215 patients who complained of frequency. They were divided into 2 groups based on age: 85 were over 65 years of age (elderly group) and 130 were less than 64 years old (adult group). Compared with the adults, elderly patients had a smaller urinary volume during waking hours and a larger volume during sleeping hours, with more frequent episodes of voiding and a smaller volume voided during the latter period. Analysis of the cause of frequency led to the patients being subdivided into 6 diagnostic categories. Among elderly patients, nocturnal polyuria (37%) and an unstable bladder (34%) were frequent causes. In adult patients an unstable bladder (28%) and polyuria due to excessive fluid intake (23%) were most common. As a result of our findings, 108 patients were advised not to be concerned about their micturition and/or restriction of fluid intake. Seventy-six patients (35%) required anticholinergic medication. Frequency-volume charts, together with a detailed medical history, provide useful information on the diagnosis and treatment of frequency.

Adolescent↗

A comparison of intensive neurodevelopmental therapy plus casting and a regular occupational therapy program for children with cerebral palsy.

The purpose of this research was to evaluate the combined effect of intensive neurodevelopmental therapy (NDT) and casting in improving hand function, quality of upper-extremity movement and range of motion in children aged between 18 months and 4 years with cerebral palsy (CP). A randomized crossover design was used to evaluate the difference between intensive NDT plus casting and a less intensive regular occupational therapy (OT) program. Blinded assessments of hand function, quality of upper-extremity movement, and parents' perception of hand-function performance were carried out at baseline, 4 months (end of first intervention period), 6 months (after a 2-month 'washout' period), and 10 months (end of second intervention period). Analysis of the outcomes revealed no significant differences in hand function, quality of upper-extremity movement, or parents' perception of hand-function performance between the two treatment groups-intensive NDT plus casting or regular OT programs. There does not appear to be any beneficial effect of an increased amount of therapy for the children in this study.

Activities of Daily Living↗