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Mathematical analysis and experiment on the corneal reflex test in spectacle wearers.

An experimental study and mathematical analysis of the corneal reflex test was undertaken in spectacle wearers. In the experimental study, photographs were taken of the corneal reflex through spectacles and the conversion ratios determined as measured in degrees/mm. In the mathematical analysis, the magnification effect of the lens was elucidated by three methods: geometrical analysis; real measurement of magnification factor; and ray tracing analysis. The real measurement of the conversion ratios was in good agreement with the conversion ratios determined by the three mathematical analyses. These results clearly showed that the corneal reflex test can be clinically useful even in wearers of spectacles.

Blinking↗

Changes in Medicare skilled nursing facility benefit admissions.

In this article, the changes in Medicare skilled nursing facility (SNF) benefit admissions from 1983 through 1985 are examined and factors that influence changes in access since the implementation of Medicare's prospective payment system are analyzed. During this period, use of the SNF benefit increased nationally by 21 percent. Multivariate analysis is used to determine factors associated with changes in admissions. Changes in SNF benefit admissions were found to be negatively associated with changes in area hospitals' lengths of stay and changes in hospitals' discharges. Medicaid reimbursement policies were also shown to affect changes in utilization.

Bed Conversion↗

Pharmacoeconomics of a pharmacist-managed program for automatically converting levofloxacin route from i.v. to oral.

The economic and clinical outcomes of a pharmacist-managed proactive program that used predetermined clinical criteria for converting levofloxacin therapy from i.v. to oral without physician approval were examined. A prospective observational study (POS) assessing the standard of care was conducted over two months and was compared with a proactive conversion program (PCP). A cost-minimization analysis was performed from the provider's perspective. The analysis was divided into cost levels 1, 2, and 3. During the POS and PCP, 49 and 82 patients were evaluated, respectively. The percentage of patients meeting conversion criteria in each group was similar (61% POS versus 65% PCP) (p = 0.827). Candidates met criteria for conversion on day 2 in both groups. The average days that conversion occurred during the POS and PCP were days 7 and 3, respectively (p = 0.010). In those patients, the length of stay was significantly shorter for the PCP (6 versus 9.5 days) (p = 0.031). Level-1, level-2, and level-3 costs were significantly less during the PCP than during the POS for patients who met conversion criteria ($77 versus $133, $91 versus $151, and $13,931 versus $17,198, respectively). Two patients in the PCP were switched back to i.v. levofloxacin due to noninfection-related complications. The overall clinical success rate for evaluable conversion candidates was 100% during the PCP. A pharmacist-managed proactive program that used predetermined clinical criteria for converting levofloxacin therapy from i.v. to p.o. without physician approval reduced length of stay and institutional health care costs without compromising clinical outcomes.

Administration, Oral↗

Regulation of the mitochondrial ATP synthase/ATPase complex: cDNA cloning, sequence, overexpression, and secondary structural characterization of a functional protein inhibitor.

The ATPase inhibitor protein of the rat liver mitochondrial ATP synthase/ATPase complex has been cloned from a rat liver cDNA library, and its nucleotide sequence determined. The sequence is highly homologous to both the bovine heart (approximately 70%) and the yeast inhibitor proteins (approximately 40%). The deduced protein sequence is 107 amino acids in length, and based on homology to the bovine heart protein, the first 25 N-terminal amino acids encode a putative mitochondrial targeting sequence. The "mature" protein (without the targeting sequence) fused to the maltose binding protein has been overexpressed in Escherichia coli. The maltose binding protein was used as a handle for the development of a rapid one-step purification of the fusion protein by affinity chromatography on an amylose resin. The purified fusion protein was cleaved with Factor Xa protease at the fusion junction, and the resulting ATPase inhibitor protein was purified to > 90% purity. The purified, overexpressed inhibitor protein displays normal inhibitor activity. The protein inhibits ATP hydrolysis catalyzed by the ATP synthase/ATPase complex in submitochondrial particles in a manner kinetically indistinguishable from the same protein purified from rat liver mitochondria, and exhibits a specific activity of approximately 10,000 units/mg. The secondary structure of the inhibitor protein was determined by circular dichroism spectropolarimetry. The experimentally determined structure shows a high content of alpha-helix and is in good agreement with sequence-based structural predictions. As the function of the inhibitor protein is known to exhibit a high dependence on pH, a study of the pH dependence of inhibitor secondary structure was performed. It is shown that as pH is lowered, conditions which activate inhibitory capacity, the protein loses significant alpha-helical structure. This is the first report of the overexpression in E. coli of a functional ATPase inhibitor protein. Secondary structural analysis of this protein indicates that conversion from its active to its inactive form involves a significant conformational change.

Adenosine Triphosphatases↗

Conversion of human-selective PPARalpha agonists to human/mouse dual agonists: a molecular modeling analysis.

To understand the species selectivity in a series of alpha-methyl-alpha-phenoxy carboxylic acid PPARalpha/gamma dual agonists (1-11), structure-based molecular modeling was carried out in the ligand binding pockets of both human and mouse PPARalpha. This study suggested that interaction of both 4-phenoxy and phenyloxazole substituents of these ligands with F272 and M279 in mouse PPARalpha leads to the species-specific divergence in ligand binding. Insights obtained in the molecular modeling studies of these key interactions resulted in the ability to convert a human-selective PPARalpha agonist to a human and mouse dual agonist within the same platform.

Animals↗

Effects of temperature and soil components on emissions from pyrolysis of pyrene-contaminated soil.

Effects of temperature and soil on yields and identities of light gases (H2, CH4, C2H2, C2H4, C2H6, CO, and CO2) and polycyclic aromatic hydrocarbons (PAH) from thermal treatment of a pyrene-contaminated (5 wt%) soil in the absence of oxygen were determined for a U.S. EPA synthetic soil matrix prepared to proxy U.S. Superfund soils. Shallow piles (140-170 mg) of contaminated soil particles and as controls, neat (non-contaminated) soil (140-160 mg), neat pyrene (10-15 mg), neat sand (230 mg), and pyrene-contaminated sand (160 mg), were heated in a ceramic boat inside a 1.65 cm i.d. pyrex tube at temperatures from 500 to 1100 degrees C under an axial flow of helium. Volatile products spent 0.2-0.4s at temperature before cooling. Light gases, PAH and a dichloromethane extract of the residue in the ceramic boat, were analyzed by gas chromatography or high pressure liquid chromatography (HPLC). Over 99% pyrene removal was observed when heating for a few tens of seconds in all investigated cases, i.e., at 500, 650, 750, 1000, and 1100 degrees C for soil, and 750 and 1000 degrees C for sand. However, each of these experiments gave significant yields (0.2-16 wt% of the initial pyrene) of other PAH, e.g., cyclopenta[cd]pyrene (CPP), which mutates bacterial cells and human cells in vitro. Heating pyrene-polluted soil gave pyrene conversions and yields of acetylene, CPP, and other PAH exceeding those predicted from similar, but separate heating of neat soil and neat pyrene. Up to 750 degrees C, recovered pyrene, other PAH, and light gases accounted for all or most of the initial pyrene whereas at 1000 and 1100 degrees C conversion to soot was significant. A kinetic analysis disentangled effects of soil-pyrene interactions and vapor phase pyrolysis of pyrene. Increase of residence time was found to be the main reason for the enhanced conversion of pyrene in the case of the presence of a solid soil or sand matrix. Light gas species released due to the thermal treatment, such as acetylene and methane, lead the formation of other, pyrene-derived PAH, e.g., methylpyrenes, cyclopenta[cd]pyrene, and benzo[a]pyrene. Implications of these findings for the chemistry of soil thermal decontamination and for diagnosing potential defects in soil thermal cleaning, e.g., incomplete elimination of targeted pollutants and formation of adverse by-products, are discussed.

Environmental Monitoring↗

[Conversion of fast insulin intensive therapy to lispro insulin in type I diabetes. Pharmacoeconomic analysis of cost-effectiveness].

In order to analyze the initial cost-effectiveness of transfer to two treatments with insulin lispro in type 1 diabetes, a pharmaco-economic study was conducted for nine months. After an educational reinforcement, a group of 30 C-peptide-negative patients (31.8 +/- 11.5 years [mean +/- SD], time since diagnosis of diabetes of 9.2 +/- 7.1 years, and on intensive therapy for 5.3 +/- 3.1 years) initiated a 3-month basal period with their usual therapy (preprandial rapid insulin and nocturnal NPH). Patients were then randomly assigned to one of the two groups, changing rapid insulin to either lispro (L1) or lispro combined with 15% to 20% NPH insulin (L2). Cross-over was made 3 months after the first treatment. Efficacy and safety were established by the assessment of HbA1c, self-monitoring blood glucose and hypoglycemia rates. Therapy cost was measured by systematic examination of the injection devices and wastage of insulin. The mean prescribed and actually consumed doses for R, L1, L2 groups were 52.9, 57.1, 55.2 U and 60.3, 64.1, 63 U per day, respectively (p < 0.001). The average of postprandial peak glucose (9.7, 8.4, 8.3 mM; p < 0.001) and HbA1c (7.6%, 7.2%, 7.1%; p < 0.01) were significantly lower after L1 or L2 lispro therapy. Although no statistical differences in overall hypoglycemia rates were observed, fewer nocturnal episodes were detected (0.72, 0.37, 0.41 events/month). The mean daily cost for regular insulin treatment was lower (186.8, 241.8; 215.7 pts and 53.7 pts per day. Efficacy and safety for two MIT regimens containing lispro were similar in the short run. Nevertheless, the preprandial use of the fast-acting insulin analog lispro in combination with a 15%-20% intermediate-acting NPH seemed to be more cost-effective than the premeal lispro therapy alone.

Adult↗

Low level laser therapy for treating tuberculosis.

BACKGROUND: The main treatment for tuberculosis is antituberculous drugs. Low level laser therapy is used as an adjunct to antituberculous drugs, predominantly in the former Soviet Union and India. OBJECTIVES: To compare low level laser therapy plus antituberculous drugs with antituberculous drugs alone for treating tuberculosis. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized Register (December 2005), CENTRAL (The Cochrane Library 2005, Issue 4), MEDLINE (1966 to December 2005), EMBASE (1974 to December 2005), CINAHL (1982 to December 2005), Science Citation Index (1945 to December 2005), PEDro (1929 to December 2005), the Central Medical Library of Moscow catalogue (1988 to June 2005), the internet, and reference lists of articles. We contacted relevant organizations and researchers for the original version. SELECTION CRITERIA: Randomized trials comparing low level laser therapy plus antituberculous drugs with antituberculous drugs alone in people with tuberculosis. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data, including adverse events. MAIN RESULTS: One randomized controlled trial (130 participants) conducted in India met the inclusion criteria. This trial was poorly reported, with no information on the generation of allocation sequence or allocation concealment. The trial report did not provide details on the group that each of the participants were randomized into or which group those participants that left the trial were from. This precluded the use of its data on time to sputum conversion and other outcome measures for analysis. AUTHORS' CONCLUSIONS: The use of low level laser therapy for treating tuberculosis is still not supported by reliable evidence. Researchers need to focus on conducting well-designed randomized controlled trials to justify the continued participation of volunteers for studies of this experimental intervention.

Humans↗

Analysis of ppb levels of organics in water by means of purge-and-trap, capillary gas chromatography and selective detectors.

The Environmental Protection Agency (EPA) has issued a series of methods (500 and 600 series) for the analysis of organics in drinking water and industrial discharges. Methods 601 and 602 employ packed-column gas chromatography (GC) with electrolytic conductivity (E1CD) and photoionization detection (PID), respectively. A purge-and-trap system is used for concentration of volatiles. The EPA is in the process of converting methods 601 and 602 and certain 500-series methods to capillary column analysis. We have also initiated the conversion of a number of these methods, using E1CD and PID and have described them in detail in this paper. We have evaluated both 0.32- and 0.53-mm diameter capillary columns, using helium and nitrogen as carrier gases with each detector. We found that with nitrogen optimum results are obtained at a flow-rate of 15 ml/min, and with helium at 6-8 ml/min. As a result of system optimization, including operation of the two detectors in series, and converting from packed to capillary columns, we found that analysis time could be reduced from 80 min (for two methods separately) to ca. 30 min. In addition, the elution of more than five components in one peak, observed when the packed column specified in method 601 are used, was eliminated.

Chromatography, Gas↗

Synthesis and characterization of N-isopropyl, N-methacryloxyethyl methacrylamide as a possible dental resin.

In this study, N-isopropyl, N-methacryloxyethyl methacrylamide (NIMM) is proposed as a possible reactive diluent in place of triethylene glycol dimethacrylate (TEGDMA) for dental resin mixtures. Real-time infrared spectroscopy was used to monitor the double-bond conversion as a function of irradiation time, and mixtures of 50/50wt% bis-GMA/NIMM were found to reach final conversions (95%) that were 1.5 times greater than bis-GMA/TEGDMA (65%) under visible light irradiation. In addition, samples cured to these conversions were tested with dynamic mechanical analysis. The bis-GMA/NIMM mixture (100% converted) was found to have a higher glass transition temperature and modulus at body temperature than a comparable bis-GMA/TEGDMA mixture (60% converted). Finally, the water sorption and solubility of bis-GMA/NIMM were determined to be higher than the bisGMA/TEGDMA comparison, but the values were still within the range of the ISO 9000s standard. These results suggest that bis-GMA/NIMM mixtures are a viable alternative to conventional dental resins since a greater degree of monomer conversion is obtainable without sacrificing physical and mechanical properties.

Dental Materials↗

Identification of two novel microalgal enzymes involved in the conversion of the omega3-fatty acid, eicosapentaenoic acid, into docosahexaenoic acid.

Marine microalgae such as Pavlova and Isochrysis produce abundant amounts of the omega3-PUFAs (polyunsaturated fatty acids), EPA (eicosapentaenoic acid, 20:5n-3) and DHA (docosahexaenoic acid, 22:6n-3). The pathway leading to the conversion of EPA into DHA in these lower eukaryotes is not well established although it is predicted to involve an elongation step, catalysed by an elongating enzyme complex, leading to the conversion of EPA into omega3-DPA (omega-3-docosapentaenoic acid, 22:5n-3); followed by a desaturation step, catalysed by a Delta4-desaturase, which results in the conversion of DPA into DHA. To date, the enzymes involved in the elongation of EPA have not been identified from any lower eukaryote. In the present study, we describe the identification of microalgal genes involved in the two-step conversion of EPA into DHA. By expressed sequence tag analysis, a gene (pavELO) encoding a novel elongase was identified from Pavlova, which catalysed the conversion of EPA into omega3-DPA in yeast. Unlike any previously identified elongase from higher or lower eukaryotes, this enzyme displayed unique substrate specificity for both n-6 and n-3 C20-PUFA substrates, with no activity towards any C18- or C22-PUFA substrates. In addition, a novel Delta4-desaturase gene (IgD4) was isolated from Isochrysis, which was capable of converting omega3-DPA into DHA, as well as adrenic acid (22:4n-6) into omega6-DPA. Yeast co-expression studies, with pavELO and IgD4, revealed that these genes were capable of functioning together to carry out the two-step conversion of EPA into DHA.

Acetyltransferases↗

[Laparoscopy-assisted colorectal resections: morbidity, conversions, outcomes of a decade].

BACKGROUND: After one decade of laparoscopic resections of the colon and rectum the parameters morbidity, conversion and complications were analyzed. The analysis of the literature comprises the results of operations performed for benign and malignant indications. METHODS: The analysis is based on the medline research of the past ten years. Publications in German language not listed were added. Results of multicenter studies were included if differentiation by indication and dignity could be achieved. Surveys of different operations of the colon and rectum not differentiated by the parameters to be analyzed were excluded. Publications of the early beginning of laparoscopic surgery were included even if not more than 10 cases were presented but the parameters described in detail. RESULTS: ADENOMAS OF THE COLON: The morbidity ranges from 0-17.4%, the conversion rate is 17.4 and 18.4% in 23 respectively 38 patients. SIGMOID DIVERTICULITIS: Mortality 0-1.8%. The morbidity was 16% in the early series and was later below 10% (8.7 and 7.3%). In the beginning the conversion rate was over 10% (12.0-38.9%) with one exception (0%). It dropped below 10% (4.6-9.2%) and was 0% in a recent study of 64 patients. The reasons for conversion are: inflammatory mass, fistula; perforation and obesity. Intraoperative complications are rare. The rate of postoperative complications did not change within 10 years (9.7 to 25.0% against 7.3 to 17.0%). CROHN'S DISEASE: The morbidity is around 10% (10.6-14.0%) and is lower in series with exclusively ileocoecal resections. The conversion rate is low or zero in ileocoecal resections and raises with the degree of inflammation and the spectrum of procedures. COLON CANCER: Mortality: 0-1.9%. The morbidity ranges from 6.8 to 30% and is especially high after conversions (up to 50%). The conversion rate reflects with the range of 4.2 to 21.0% in the beginning and 1.6 to 23.5% later the experience of the individual surgeon. RECTAL CANCER: Even in large series (n = 157) the mortality of laparoscopic rectal resections is zero. The conversion rate is 0-7.6%; the morbidity 11.5 to 26.4%. REVERSAL OF HARTMANN PROCEDURE: The number of cases is low, the conversion rate is around 20%. The morbidity ranges from 14.3-41.1% with one exception (0%). RECTOPEXY: Four different techniques are applied laparoscopically. The morbidity ranges from 0 to 16%. The conversion rate is 0-2.6%, except one (16.0%). CONCLUSION: After one decade of laparoscopic colorectal surgery there are advantages for benign indications (adenomas, Crohn's disease, rectopexy) when compared with open surgery. Disadvantages arise from conversions. Experience of the surgeon is a strong parameter for a successful outcome. Results of ongoing studies are awaited for malignant indications.

Adenoma↗

A radiation hybrid map of 15 loci on the distal long arm of chromosome 4, the region containing the gene responsible for facioscapulohumeral muscular dystrophy (FSHD).

A physical map of 4q35 was constructed through radiation hybrid analysis of 134 clones generated from the cell line HHW416, a chromosome 4-only human-hamster somatic cell hybrid. This subtelomeric region contains the as-yet-unidentified gene responsible for facioscapulohumeral muscular dystrophy. The most likely order of 15 loci within 4q35 was determined. The loci ordered on this radiation hybrid map include both genes and polymorphic loci, as well as monomorphic loci which cannot be placed on a genetic linkage map. The physical distance spanning these loci was estimated to be approximately 4.5 Mb, by using a kilobase/centiray conversion factor derived from 4p16.3 marker analysis through the same set of radiation hybrids. The comparison of this physical map to establish genetic maps suggests that this region is smaller than initially estimated and that recombination rates are increased near the telomere.

Animals↗

Monomer conversion versus flexure strength of a novel dental composite.

OBJECTIVES: To quantify the monomer conversion and flexural strength of an experimental oxirane-based composite material (EXL596) compared with two, commercially available, dimethacrylate based restoratives (Z250 and Z100). METHODS: Fourier-transform infra-red spectroscopy (FTIR) was utilised to evaluate the degree of conversion (DC) (n=5) and biaxial flexure strength (BFS) testing (n=20) was used to analyse flexural strength and associated Weibull moduli (m) of each material following 0.1, 0.5, 1, 4, 24 and 48 h immersion in a lightproof waterbath maintained at 37+/-1 degrees C. RESULTS: The DC of Z250 and Z100 following 0.1, 0.5 and 1 h post-irradiation was significantly greater than the DC of EXL596 for the same immersion periods. This was manifested as a significant decrease in BFS and associated m of EXL596 compared with Z250 and Z100 for the 0.1, 0.5 and 1 h post-irradiation periods. The DC and BFS of EXL596 were significantly greater than Z250 and Z100 following 24 h immersion. CONCLUSIONS: Assessment of FTIR spectra, BFS and associated m has provided a useful method in the quantitative analysis of resin-based composite conversion. Identification of the decreased DC of EXL596 compared with Z250 and Z100 was achieved using FTIR. However, decreased conversion rates within the first hour following irradiation of EXL596 may compromise flexural strength properties (associated with a decrease in BFS and m) which may be inadequate under masticatory loading.

Analysis of Variance↗

Comparison of the expression of calcitonin receptor-like receptor (CRLR) and receptor activity modifying proteins (RAMPs) with CGRP and adrenomedullin binding in cell lines.

1. The calcitonin receptor-like receptor (CRLR) and specific receptor activity modifying proteins (RAMPs) together form receptors for calcitonin gene-related peptide (CGRP) and/or adrenomedullin in transfected cells. 2. There is less evidence that innate CGRP and adrenomedullin receptors are formed by CRLR/RAMP combinations. We therefore examined whether CGRP and/or adrenomedullin binding correlated with CRLR and RAMP mRNA expression in human and rat cell lines known to express these receptors. Specific human or rat CRLR antibodies were used to examine the presence of CRLR in these cells. 3. We confirmed CGRP subtype 1 receptor (CGRP(1)) pharmacology in SK-N-MC neuroblastoma cells. L6 myoblast cells expressed both CGRP(1) and adrenomedullin receptors whereas Rat-2 fibroblasts expressed only adrenomedullin receptors. In contrast we could not confirm CGRP(2) receptor pharmacology for Col-29 colonic epithelial cells, which, instead were CGRP(1)-like in this study. 4. L6, SK-N-MC and Col-29 cells expressed mRNA for RAMP1 and RAMP2 but Rat-2 fibroblasts had only RAMP2. No cell line had detectable RAMP3 mRNA. 5. SK-N-MC, Col-29 and Rat-2 fibroblast cells expressed CRLR mRNA. By contrast, CRLR mRNA was undetectable by Northern analysis in one source of L6 cells. Conversely, a different source of L6 cells had mRNA for CRLR. All of the cell lines expressed CRLR protein. Thus, circumstances where CRLR mRNA is apparently absent by Northern analysis do not exclude the presence of this receptor. 6. These data strongly support CRLR, together with appropriate RAMPs as binding sites for CGRP and adrenomedullin in cultured cells.

Adrenomedullin↗

Differential effects of hyperoxia on the inducible and constitutive isoforms of nitric oxide synthase in the lung.

Hyperoxia is commonly used in the treatment of newborn respiratory distress. Although essential and life saving, oxygen therapy can result in the development of lung injury. Oxygen toxicity is associated with the production of reactive oxidant species. Nitric oxide (NO) is an oxidant formed by the catalysis of L-arginine when acted upon by the enzyme nitric oxide synthase (NOS). We studied the differential effects of prolonged normobaric hyperoxia (FIO2 = .95, for 3, 4, and 5 days) on the two major NOS enzymes, constitutive endothelial cell NOS (ecNOS) and inducible NOS (iNOS). Hyperoxia led to a significant lung injury, as measured by pulmonary compliance studies. Hyperoxia did not increase serum NO production, measured as the concentration of nitrite and nitrate. However, hyperoxia did result in a small but significant increase in NO production in the bronchoalveolar lavage fluid, as measured by the products of nitrite and nitrate concentration. This increase in NO was not associated with an induction of whole lung iNOS, as measured by the conversion of L-[3H]arginine to L-[3H]citrulline or by Northern blot analysis. Hyperoxia significantly decreased ecNOS activity as measured by the conversion of L-[3H]arginine to L-[3H]citrulline. In addition, administration of the NOS inhibitor NG-nitro-L-arginine methyl ester worsened the injury, as measured by lung compliance and survival. Further studies need to be performed to determine whether this decrease in ecNOS activity during hyperoxia plays a role in the pathogenesis of hyperoxia-related lung injury.

Animals↗