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Genotoxic effectivity--comparison of 36 nitrated furan and arenofuran derivatives on a quantitative scale. Statistical comparison of T7 and other short-term tests.

Thirty-six nitrated furan and arenofuran derivatives were measured and quantitatively characterized by the T7 inactivation test. A wide range of substances previously studied allowed us to compare the collected quantitative data with those obtained by other workers using different short-term tests. Based on comparative statistical evaluation of these data a borderline was determined for the genotoxic effect: compounds having in our short-term test mutagenicity index (MI) values smaller than 8.0 are positive while the higher values represent negative genotoxicity. Classification of 36 nitrofuran/nitroarenofuran derivatives is given both on the basis of the quantitative genotoxicity scale and in terms of +/- on the qualitative scale. All but one compound were found to be genotoxic and the genotoxic activities of these compounds were compared with the results of other carcinogenicity or mutagenicity tests.

Carcinogenicity Tests↗

A comparison of optimal and suboptimal RNA secondary structures predicted by free energy minimization with structures determined by phylogenetic comparison.

This article describes the latest version of an RNA folding algorithm that predicts both optimal and suboptimal solutions based on free energy minimization. A number of RNA's with known structures deduced from comparative sequence analysis are folded to test program performance. The group of solutions obtained for each molecule is analysed to determine how many of the known helixes occur in the optimal solution and in the best suboptimal solution. In most cases, a structure about 80% correct is found with a free energy within 2% of the predicted lowest free energy structure.

Algorithms↗

Determination of 234U/238U ratio: comparison of multi-collector ICPMS and ICP-QMS for water, hair and nails samples, and comparison with alpha-spectrometry for water samples.

The (234)U/(238)U ratio in water, hair and nails samples was determined by multi-collector inductively coupled plasma mass spectrometry (MC-ICPMS) and inductively coupled plasma quadrupole mass spectrometry (ICP-QMS) and by alpha-spectrometry for the water samples only. A correlation of 0.99 was found between the two ICPMS methods and of 0.98 with alpha-spectrometry. The range of activity ratios was between 0.9 and 2.6 according to the MC-ICPMS measurements. The reproducibility of both ICPMS techniques was better than 4% for water samples containing 1 mug l(-1) of uranium and a (234)U/(238)U atom ratio of 54.9 x 10(-6). Sample preparation for the ICPMS consisted of dilution of water samples containing >10 microg l(-1) of uranium and measurement time was approximately 1 min, while alpha-spectrometry involved pre-concentration and separation of the uranium and counting times of 1,000 min.

Body Burden↗

Limitations of the cervical porcine spine in evaluating spinal implants in comparison with human cervical spinal segments: a biomechanical in vitro comparison of porcine and human cervical spine specimens with different instrumentation techniques.

STUDY DESIGN: Porcine and human cervical spine specimens were in vitro biomechanically compared with different instrumentation techniques. OBJECTIVES: To evaluate whether subaxial porcine cervical spines are a valid model for implant testing in a single level corpectomy. SUMMARY OF BACKGROUND DATA: Biomechanical in vitro tests are widely used for implant tests, mainly with human spine specimens. The availability of human cadavers is limited and the properties of the specimen regarding age, bone mineral density, and grade of degenerative changes is inhomogeneous. METHODS: Six porcine and six human cervical specimens were loaded nondestructively with pure moments: 1) in an intact state; 2) after a corpectomy of C5 and substitution by a cage with integrated force sensor; 3) after additional instrumentation with a posterior screw and rod system with: a) lateral mass and b) pedicle screws; 4) after instrumentation with an anterior plate; and 5) with a circumferential instrumentation. The unconstrained motion and the axial loads occurring in the corpectomy gap were measured, as well as the bone mineral density of the specimen before testing. RESULTS: The range of motion in the intact state, as well as for the different instrumentations, was comparable for flexion-extension. In lateral bending and axial rotation, marked differences in the intact state as well as for pedicle screw instrumentations occurred. CONCLUSIONS: The subaxial porcine cervical spine is a potential model in flexion-extension because of its biomechanical similarity. For lateral bending and axial rotation, the marked differences severly restrict the comparability.

Aged↗

Tube-feeding versus hand-feeding nursing home residents with advanced dementia: a cost comparison.

OBJECTIVE: To compare the costs associated with caring for severely demented residents nursing homes with and without feeding tubes. DESIGN: Retrospective cohort study. SETTING: A 700-bed long-term care facility in Boston Participants: Nursing home residents aged 65 years and over with advanced dementia and eating problems for whom long-term feeding tube had been discussed as a treatment option. MEASUREMENTS: Costs were compared over the 6 months that followed the tube-feeding decision for those residents who did and did not undergo feeding tube placement for the following items: nursing time, physician assessments, food, hospitalizations, emergency room visits, diagnostic tests, treatment with antibiotics and parenteral hydration, and feeding tube insertion. RESULTS: Twenty-two subjects were included, 11 were tube-fed (mean age 84.3 years +/- 6.0) and 11 were hand-fed (mean age 90.2 years +/- 9.1). The daily costs of nursing home care were higher for the residents without feeding tubes compared with residents with tubes ($4219 +/- 1546 vs $2379 +/- 1032, P = 0.006). Nonetheless, Medicaid reimbursement to nursing homes in at least 26 states is higher for demented residents who are tube-fed than for residents with similar deficits who are not tube-fed. Costs typically billed to Medicare were greater for the tube-fed patients ($6994 +/- 5790 vs. $959 +/- 591, P < 0.001), primarily because of the high costs associated with initial feeding tube placement and hospitalizations or emergency rooms visits for the management of complications of tube-feeding. CONCLUSIONS: Nursing homes are faced with a potential fiscal incentive to tube-feed residents with advanced dementia: tube-fed residents generate a higher daily reimbursement rate from Medicaid, yet require less expensive nursing home care. From a Medicare perspective, tube-fed patients are expensive due to the high costs associated with feeding tube placement and acute management of complications. Further work is needed to determine whether these potential financial incentives influence tube-feeding decisions in practice.

Activities of Daily Living↗

A comparison of haemagglutination, haemagglutination inhibition and PCR for the detection of psittacine beak and feather disease virus infection and a comparison of isolates obtained from loriids.

Psittacine beak and feather disease (PBFD) is recognized as a threat for endangered psittacine birds in Australia, New Zealand and South Africa. Several diagnostic methods for the detection of beak and feather disease virus (BFDV) infection have been developed but there are few studies comparing the relative merits or sensitivity and specificity of each diagnostic test. In this report, the results of PCR, haemagglutination (HA) and haemagglutination inhibition (HI) testing of diagnostic samples collected from 679 samples from a range of psittacine bird species suspected of being infected with BFDV are summarized and compared. There was a strong agreement (kappa = 0.757; P<0.0001) between PCR and HA testing of feather samples and PCR-negative birds were 12.7 times more likely to have HI antibody than PCR-positive birds. False-positive HA results with titres up to 1:320 were identified in six feather samples that were PCR negative; the haemagglutination detected in these samples was not inhibited by anti-BFDV antisera and was removed by filtration through a 0.22 microm filter. Similarly, one false-negative PCR result was detected in a feather sample that had a high HA titre (>1:40,960) and four false-positive PCR results were detected in a batch of four feather samples. Of 143 birds that were feather PCR positive, only two had detectable HI antibody, and these birds were also feather HA negative, suggesting that they were developing immunity to recent infection. All birds with HI antibody were negative on feather HA testing. The assays confirmed BFDV infection in two endangered swift parrots (Lathamus discolor) and phylogenetic analysis of the sequence data generated from ORF V1 of these isolates provide further evidence of BFDV genotypes clustering in parallel with the Loriidae, Cacatuidae and Psittacidae.

Animals↗

Biochemical comparison of the Neurospora crassa wild type and the temperature-sensitive and leucine-auxotroph mutant leu-5. Purification of the cytoplasmic and mitochondrial leucyl-tRNA synthetases and comparison of the enzymatic activities and the degradation patterns.

The cytoplasmic leucyl-tRNA synthetases of Neurospora crassa wild type (grown at 37 degrees C) and mutant (grown at 28 degrees C) were purified approximately 1770-fold and 1440-fold respectively. Additional enzyme preparations were carried out with mutant cells grown for 24 h at 28 degrees C and transferred then to 37 degrees C for 10-70 h of growth. The mitochondrial leucyl-tRNA synthetase of the wild type was purified approximately 722-fold. The mitochondrial mutant enzyme was found only in traces. The cytoplasmic leucyl-tRNA synthetase from the mutant (grown at 37 degrees C) in vivo is subject of a proteolytic degradation. This leads to an increased pyrophosphate exchange, without altering aminoacylation. Proteolysis in vitro by trypsin or subtilisin of isolated cytoplasmic wild-type and mutant leucyl-tRNA synthetases, however, did not establish and difference in the degradation products and in their catalytic properties. Comparing the cytoplasmic wild-type and mutant enzymes (grown at 28 degrees C) via steady-state kinetics did not show significant differences between these synthetases either. The rate-determining step appears to be after the transfer of the aminoacyl group to the tRNA, e.g. a conformational change or the release of the product. Besides leucine only isoleucine is activated by the enzymes with a discrimination of approximately 1:600; however, no Ile-tRNALeu is released. Similarly these enzymes, when tested with eight ATP analogs, cannot be distinguished. For both enzymes six ATP analogs are neither substrates nor inhibitors. Two analogs are substrates with identical kinetic parameters. The mitochondrial wild-type leucyl-tRNA synthetase is different from the cytoplasmic enzyme, as particularly exhibited by aminoacylating Escherichia coli tRNALeu but not N. crassa cytoplasmic tRNALeu. The presence of traces of the analogous mitochondrial mutant enzyme could be demonstrated. Therefore, the difference between wild-type and mutant leu-5 does not rest in the catalytic properties of the cytoplasmic leucyl-tRNA synthetases. Differences in other properties of these enzymes are not excluded. In contrast the activity of the mitochondrial leucyl-tRNA synthetase of the mutant is approximately 1% of that of the wild-type enzyme.

Adenosine Triphosphate↗

Biochemical comparison of the Neurospora crassa wild-type and the temperature-sensitive leucine-auxotroph mutant leu-5. Detailed kinetic comparison of the leucyl-tRNA synthetases.

The cytoplasmic leucyl-tRNA synthetases were purified from a wild-type Neurospora crassa and from a temperature-sensitive leucine-auxotroph (leu-5) mutant. A detailed steady-state kinetic study of the aminoacylation of the tRNALeu from N. crassa by the purified synthetases was carried out. These enzymes need preincubation with dithioerythritol and spermine before the assay in order to become fully active. The Kappm value for leucine was lowered by high ATP concentrations and correspondingly the Kappm,ATP was lowered by high leucine concentrations. The Kappm,Leu was lowered by high pH, a pK value of 6.7 (at 30 degrees C) was calculated for the ionizable group affecting the Km. At the concentrations of 2 mM ATP, 20 microM leucine, 0.3 microM tRNALeu, and pH 7 the apparent Km values were Kappm,ATP = 1.3 mM, Kappm,Leu = 49 microM and Kappm,tRNA = 0.15 microM. No essentially altered cytoplasmic leucyl-tRNA synthetase was produced by the temperature-sensitive mutant strain when kept at 37 degrees C. In none of these experiments could we find any difference between the wild-type enzyme and the enzyme from the mutant strain (whether grown at permissive temperature, 28 degrees C, or grown at permissive temperature for 24 h followed by growth at 37 degrees C). We therefore think that the small difference in the Km value for leucine of the wild-type and mutant enzyme, established in some earlier investigations, is not due to a difference in the kinetic properties of the enzyme molecules but to an external influence. The almost total lack of the mitochondrial leucyl-tRNA synthetase in the mutant strain besides the leucine autotrophy remains the only difference between the wild-type and mutant strains.

Adenosine Triphosphate↗

A long-term comparison of pioglitazone and gliclazide in patients with Type 2 diabetes mellitus: a randomized, double-blind, parallel-group comparison trial.

AIMS: This study compared the effects of pioglitazone and gliclazide on metabolic control in drug-naive patients with Type 2 diabetes mellitus. METHODS: A total of 1270 patients with Type 2 diabetes were randomized in a parallel-group, double-dummy, double-blind study. Patients with poorly controlled Type 2 diabetes (HbA1c 7.5-11%), despite dietary advice, received either pioglitazone up to 45 mg once daily or gliclazide up to 160 mg two times daily. Primary efficacy endpoint was change in HbA1c from baseline to the end of the study. Secondary efficacy endpoints included change in fasting plasma glucose, fasting plasma insulin and plasma lipids. At selected centres, oral glucose tolerance tests were performed and C-peptide and pro-insulin levels were measured. RESULTS: Mean HbA1c values decreased by the same amount in the two treatment groups from baseline to week 52 [pioglitazone: -1.4%; gliclazide: -1.4%; (90% CI: -0.18 to 0.02)]. A significantly greater mean reduction in fasting plasma glucose was observed in the pioglitazone group (2.4 mmol/l) than in the gliclazide group [2.0 mmol/l; treatment difference -0.4 mmol/l in favour of pioglitazone; P = 0.002; (95% CI: -0.7 to -0.1)]. Improvements in high-density lipoprotein cholesterol (HDL-C) and total cholesterol/HDL-C were greater with pioglitazone than with gliclazide (P < 0.001). The frequencies of adverse events were comparable between the two treatment groups, but more hypoglycaemic events were reported for gliclazide, whereas twice as many patients reported oedema with pioglitazone than with gliclazide. CONCLUSIONS: Pioglitazone monotherapy was equivalent to gliclazide in reducing HbA1c, with specific differences between treatments in terms of mechanism of action, plasma lipids and adverse events.

Adult↗

Nosological comparisons of DSM-III-R and DSM-IV alcohol abuse and dependence in a clinical facility: comparison with the 1988 National Health Interview Survey results.

The purpose of this study was to compare DSM-III-R and proposed formulations of DSM-IV diagnoses of alcohol use disorders in a clinical sample with the same assessment methods used in a large national survey previously reported. Issues included the number of symptoms required for abuse and dependence diagnoses, the effects of requiring evidence of physiological dependence to make the dependence diagnosis (Option 1 vs. Option 2), whether to require a duration criterion, and the concept of alcohol abuse. The diagnostic criteria proposed in the 1991 DSM-IV options book were the criteria investigated in this study. Concordance between DSM-III-R and DSM-IV was closest when the form of DSM-IV used was most similar to DSM-III-R. The duration criterion had much less effect on a dependence diagnosis in this clinical sample than in the general population. DSM-IV Option 2 for alcohol dependence excluded a number of cases from the dependence diagnosis who received such a diagnosis under DSM-III-R and DSM-IV Option 1. Abuse continued to function as a residual category, especially noticeable under increasingly restrictive definitions of dependence, and was rare in both the clinical and general population sample. Implications of the findings for research and other purposes are discussed.

Adolescent↗

Comparison of the BACTEC MYCO/F Lytic bottle to the isolator tube, BACTEC Plus Aerobic F/bottle, and BACTEC Anaerobic Lytic/10 bottle and comparison of the BACTEC Plus Aerobic F/bottle to the Isolator tube for recovery of bacteria, mycobacteria, and fungi from blood.

The BACTEC MYCO/F Lytic blood culture bottle (Becton Dickinson Diagnostic Instrument Systems, Sparks, Md.) is designed to optimize the recovery of fungi and mycobacteria; however, this bottle also supports the growth of most aerobic bacteria. We compared the MYCO/F Lytic bottle with two other BACTEC bottles and the Isolator system for the recovery of bacteria as well as fungi and mycobacteria from blood. A total of 6,108 blood culture sets were inoculated with blood obtained from adult patients. Twenty-five to 28 ml of blood collected by a phlebotomy team for each blood culture set was randomly distributed into each of four blood culture receptacles: the Isolator tube (Wampole Laboratories, Cranbury, N.J.) and three BACTEC bottles: the MYCO/F Lytic bottle, the BACTEC Plus Aerobic/F bottle, and the BACTEC Anaerobic Lytic/10 bottle. The sediment from the Isolator tube was inoculated onto chocolate agar (CA), brain heart infusion agar (BHI), and Sabouraud dextrose agar (SDA) and into a BACTEC 13A bottle. Incubation durations were as follows: MYCO/F Lytic bottle, 42 days; Plus Aerobic/F bottle, 5 days; Anaerobic Lytic/10 bottle, 5 days; sediment from Isolator tube on CA, 3 days; sediment from Isolator tube on BHI, 30 days; sediment from Isolator tube on SDA, 30 days; and sediment from Isolator tube in a BACTEC 13A bottle, 42 days. Two isolates of Histoplasma capsulatum were recovered from the Isolator tube only. Three isolates of Mycobacterium tuberculosis complex were recovered: two isolates from the MYCO/F Lytic bottle only and one isolate from the Isolator tube (whose sediment was inoculated into the BACTEC 13A bottle) only. Two isolates of Cryptococcus neoformans were recovered: one from the MYCO/F Lytic bottle only and the other from the MYCO/F Lytic bottle and the Isolator tube (whose sediment was inoculated into the BACTEC 13A bottle). For potential pathogens overall, there was a statistical difference in recovery that favored the Isolator system over the MYCO/F Lytic bottle (P = 0.0015), including statistically significant differences for Staphylococcus aureus (P = 0.0001) and Streptococcus pneumoniae (P = 0.0313). However, there was no statistically significant difference between the two blood culture systems when detection of bloodstream infection was considered. The time to detection for all potential pathogens combined was less for the MYCO/F Lytic bottle than for the Isolator system (P = 0.0004). Overall, the potential pathogen recovery was greater for the BACTEC Plus Aerobic/F bottle than for either the Isolator system (P = 0.0003) or the MYCO/F Lytic bottle (P = 0.0001). However, the BACTEC Plus Aerobic/F bottle did not recover M. tuberculosis, H. capsulatum, or C. neoformans isolates. The combination of the Isolator system and MYCO/F Lytic bottle may be useful as a selective blood culture method to optimize the recovery of fungi and mycobacteria from blood. Compared with the manual Isolator system, the MYCO/F Lytic system has the advantage of less preanalytic processing and continuous automated monitoring of bottles for growth by the BACTEC 9240 instrument.

Adult↗

Interspecies comparison of calmodulin binding proteins throughout the gastrointestinal tract: comparison with human colon adenomas and adenocarcinomas.

Calmodulin is an ubiquitous cytoplasmic protein which mediates many of the actions of calcium on intestinal tissue including regulation of growth and differentiation of normal and neoplastic cells. Using a biotinylated calmodulin overlay system, we compared the pattern of calmodulin binding proteins throughout the gastrointestinal tract of mice, rats, rabbits, and humans, and in human colonic adenomas and adenocarcinomas. A common calmodulin binding protein of 67 kDa was found in membrane and cytosolic fractions of oesophagus, stomach, proximal and distal small intestine, and colon from all four species. In human tissue this 67 kDa protein was present in greatest concentration in stomach tissue. Furthermore, a 67 kDa binding protein was the major calmodulin binding protein from human stomach and ileum as determined by ion exchange and calmodulin affinity chromatography. A similar pattern of binding proteins was noted between rabbit and human cytosolic fractions; proteins of 60/67 kDa and 105 kDa were present in stomach tissue. A 94 kDa protein was present in samples of rabbit and human ileum but not of mouse or rat. A similar pattern of calmodulin binding proteins was seen in normal and neoplastic large bowel tissue, apart from one of nine adenocarcinomas, where a distinct 54 kDa band was noted in both cytosolic and membrane fractions. The results of this study show interspecies and organ differences between calmodulin binding proteins, but suggest that a 67 kDa protein is the major binding protein present throughout normal gastro-intestinal tract and neoplastic human tissue.

Adenocarcinoma↗

A COMPARISON OF PLATELET AGGREGATION PRODUCED BY SEVEN COMPOUNDS AND A COMPARISON OF THEIR INHIBITORS.

The aggregating effects of adenosine diphosphate, thrombin, 5-hydroxytryptamine, tryptamine, adrenaline and noradrenaline, and tri-ethyl tin have been carefully compared. The first three compounds in some circumstances produce remarkably similar effects although there are important differences. The kinetics of aggregation induced by adrenaline (and noradrenaline) are quite different and the tri-ethyl tin effects are different again. Anti-serotonins specifically inhibit 5-hydroxytryptamine and the anti-adrenaline drug phentolamine specifically inhibits the effects of the catecholamines. Experiments presented suggest but do not prove that aggregation produced by all these compounds is accompanied by the liberation of diphosphate from the platelets and that platelet triphosphate may be converted to diphosphate. How these different compounds all produce this effect is discussed. Either the presence of diphosphate or the action of a triphosphatase might be the immediate cause of aggregation if there is a single final common cause. The anti-adrenaline phentolamine prolongs the bleeding time, so adrenaline or noradrenaline may be involved in platelet phenomena in haemostasis.

Adenine Nucleotides↗

Computer printing and filing of microbiology reports. 2. Evaluation and comparison with a manual system, and comparison of two manual systems.

A manual system of microbiology reporting with a National Cash Register (NCR) form with printed names of bacteria and antiboitics required less time to compose reports than a previous manual system that involved rubber stamps and handwriting on plain report sheets. The NCR report cost 10-28 pence and, compared with a computer system, it had the advantages of simplicity and familarity, and reports were not delayed by machine breakdown, operator error, or data being incorrectly submitted. A computer reporting system for microbiology resulted in more accurate reports costing 17-97 pence each, faster and more accurate filing and recall of reports, and a greater range of analyses of reports that was valued particularly by the control-of-infection staff. Composition of computer-readable reports by technicians on Port-a-punch cards took longer than composing NCR reports. Enquiries for past results were more quickly answered from computer printouts of reports and a day book in alphabetical order.

Attitude↗

Comparison of ventricular enlargement and radiopharmaceutical retention: a cisternographic-pneumoencephalographic comparison.

The cisternograms and pneumoencephalograms of 58 patients with suspected "normal pressure" hydrocephalus were correlated and the relationship of ventricular radiopharmaceutical entry and stasis to ventricular size was analyzed. It was found that radiopharmaceutical entry relates directly to ventricular size, stasis occurring only in markedly enlarged ventricles. Cerebrospinal fluid imaging alone is a highly reliable diagnostic study only if patients exhibit the characteristic cisternographic patterns of normal pressure hydrocephalus. In those who do not, pneumoencephalography and cisternography are valuable complementary studies which can also be used to identify primary cortical atrophy.

Cerebral Ventriculography↗