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PubMed2006

Innovative schedule of oral idarubicin in elderly patients with metastatic breast cancer: comprehensive results of a phase II multi-institutional study with pharmacokinetic drug monitoring.

BACKGROUND: To determine if protracted low-dose oral idarubicin (IDA), feasible in a previous dose-finding study, would result in similar activity and a better toxicity profile in patients with metastatic breast cancer. PATIENTS AND METHODS: Elderly women (> or=65 years) with metastatic breast carcinoma were treated with 7.5 mg/day for 21 consecutive days, every 4 weeks. After the first fourteen patients, due to excessive toxicity, the protocol was amended to 5 mg/day. IDA and Idarubicinol (IDOL) plasma concentrations (C(trough)) were investigated in all patients. RESULTS: Between April 1999 and June 2004, 47 elderly patients were accrued in this two-part study (14 and 33 patients respectively). The median age was 74 and 75 years respectively. Visceral involvement was present in most patients. A partial response was noted in 7/31 patients (22%; 95% CI, 9.6-41.1%). Eleven patients had stable disease (33%). At the dose of 5 mg/day the treatment was well tolerated. Neutropenia grade 4 was present in only 6% of patients; alopecia > grade 1 and cardiotoxicity did not occur. The median time to progression was 3 months and the median overall survival was 17 months. IDA C(trough) and IDOL C(trough) levels were significantly associated with haematologic toxicity. CONCLUSION: This study shows that idarubicin at the dose of 5 mg/day for 21 consecutive days is feasible and effective in elderly breast cancer patients but do not demonstrate an improvement in efficacy. A determination of the IDA and IDOL plasma levels (C(trough)) is predictive for toxicity.

Administration, Oral↗
PubMed1988

Two methods for examining angular response of personnel dosimeters.

The American National Standard ANSI N13.11-1983 is used to test the accuracy (bias plus precision) of dosimetry processors as part of the dosimetry accreditation program of the National Voluntary Laboratory Accreditation Program (NVLAP). Section 3.8 of the ANSI N13.11-1983 standard requires that a study of the angular response of a dosimeter be carried out once, although no pass/fail criterion is given for angular response. The NVLAP accreditation program excluded Section 3.8, and thus no angular response data have been generated in an organized fashion. The objective of this project is to examine the feasibility of two alternative methods to test the angular response of personnel dosimeters. The first alternative involves static irradiations with the dosimeters at fixed angles to a radiation source. The second alternative involves dynamic irradiations with the dosimeters mounted on a rotating phantom. A Panasonic UD-802 personnel dosimetry system** was used to generate data to examine both alternatives. The results lead to two major conclusions. Firstly, Section 3.8 of the ANSI N13.11-1983 standard should be amended to require a pass/fail test for angular response. Secondly, a comparison between angular response data generated with a fixed or a rotating phantom shows that the rotating phantom is the more cost-effective method.

Algorithms↗
PubMed1985

Glycine-Glomus-Rhizobium Symbiosis: II. Antagonistic Effects between Mycorrhizal Colonization and Nodulation.

Soybean (Glycine max [L.] Merr.) plants grown in pot cultures were inoculated with the vesicular-arbuscular mycorrhizal (VAM) fungus Glomus mosseae (Nicol. & Gerd.) Gerd. and Trappe and Rhizobium japonicum strain 61A118 at planting (G(1)R(1)) or at 20 days (G(20)R(20)), or with one of the endophytes after the other has colonized the host root (G(1)R(20), G(20)R(1)). Nodulated (PR(1)) and VAM (G(1)N) dipartite associations, or nonsymbiotic plants (PN) using nutrient solutions with N, P, or N + P concentrations providing endophyte-equivalent nutrient inputs were used as controls. The delayed tripartite associations received the appropriate N, P, or N + P amendment while one or both endophytes were absent during the first 20 days of growth. Prior inoculation with one endophyte significantly inhibited development of the other. Root hexose sugar concentrations were negatively correlated with VAM colonization (r = -0.89), nodule activity (r = -0.91), and root P content (r = -0.93). Nodule (r = 0.97) and root (r = 0.96) P content correlated positively with VAM colonization. Nodule weight or VAM-fungal biomass were significantly greater in associations grown with only one endophyte. Dry weights of the PN, G(1)N, PR(1), and G(20)R(20) plants were significantly greater than those of tripartite plants inoculated at planting with either or both endophytes. Interendophyte inhibition is attributed to competition for root carbohydrates, and this effect apparently also affects overall plant productivity. The objective of the study was to determine if the timing of endophyte introduction and establishment affected the development of the other symbiotic partners.

Journal Article↗
PubMed1990

Survival of genetically engineered Escherichia coli in natural soil and river water.

Twelve derivatives of Escherichia coli strain HB101 which contained different sizes of plasmids ranging from 3.9 Kb to 48 Kb and encoding resistance to various antibiotics were used. When these organisms were introduced into natural river water, the population declined rapidly and by day 3, the majority (i.e. more than 99.9%) of them could no longer be detected on antibiotic-amended culture plates. If the river water was filter sterilized first, the added organisms maintained their population for up to 7 d without any significant decrease in numbers. Similar results were also observed in sterilized tap water or distilled water. This indicated that the disappearance of these organisms in the aquatic environment was caused mainly by biotic factor(s). The loss of the ability to grow in the presence of antibiotics by some of the E. coli was not observed unless they were allowed to grow in the antibiotic-free environment first. When the test organisms were added to natural silt loam, a large portion of the original population still remained viable after 16 d. There was no relationship between the percentage survival of E. coli in natural river water and the sizes of plasmid harboured. On the other hand, when these bacteria were added to natural soil, survival appeared to increase as plasmid size increased.

Drug Resistance, Microbial↗
PubMed2005

Mental health nurse practitioners in Australia: improving access to quality mental health care.

Under The Nurses Amendment (Nurse Practitioners) Act 1998, New South Wales became the first state in Australia to legislate for nurse practitioners. Mental health was identified as a priority 'area of practice' for nurse practitioners. Issues surrounding the implementation of the nurse practitioner role in Australia and the potential for the role to address the current crisis in mental health nursing and the mental health sector will be discussed. The potential for partnerships with other health-care providers, in particular medical practitioners, will demonstrate how successful implementation of the role can fulfil consumer demand for primary prevention counselling, improve access to mental health services and early intervention, and provide mental health services that better reflect national priorities. This examination of the Australian context will be contrasted with a review of the overseas literature on mental health nurse practitioners.

Attitude of Health Personnel↗
PubMed1993

Nitrogen limitation and nitrogen fixation during alkane biodegradation in a sandy soil.

We investigated nutrient limitations during hydrocarbon degradation in a sandy soil and found that fixed nitrogen was initially a limiting nutrient but that N limitation could sometimes be overcome by N2 fixation. Hydrocarbon biodegradation was examined in an unsaturated sandy soil incubated aerobically at 20 degrees C with propane or butane and various added nutrients. Propane and butane degradation proceeded similarly during the first 3 months of incubation. That is, bacteria in soil amended with N oxidized these hydrocarbons more rapidly than in controls without nutrient additions or in soil with added phosphate or trace minerals. Both propane- and butane-amended soil apparently became N limited after the initial available inorganic N was utilized, as indicated by a decrease in the rates of hydrocarbon degradation. After 3 months, propane and butane degradation proceeded differently. Bacteria in propane-degrading soil apparently remained N limited because propane degradation rates stayed low unless more N was added. In contrast, bacteria in butane-degrading soil appeared to overcome their N limitation because butane degradation rates later increased regardless of whether more N was added. Analyses of total N and acetylene reduction assays supported this apparent surplus of N in butane-amended soil. Total N was significantly (P < 0.01) higher in soil incubated with butane and no N amendments than in soil incubated with propane, even when the latter was amended with N. Acetylene reduction occurred only in butane-amended soil. These results indicate that N2 fixation occurred in butane-amended soil but not in propane-amended soil.

Acetylene↗
PubMedDate not supplied

Enhanced phenanthrene biodegradation in soil by slender oat root exudates and root debris.

To investigate the mechanisms by which slender oat (Avena barbata Pott ex Link) enhances phenanthrene biodegradation, we analyzed the impacts of root exudates and root debris on phenanthrene biodegradation and degrader community dynamics. Accelerated phenanthrene biodegradation rates occurred in soils amended with slender oat root exudates as well as combined root debris + root exudate as compared with unamended controls. Root exudates significantly enhanced phenanthrene biodegradation in rhizosphere soils, either by increasing contaminant bioavailability and/or increasing microbial population size and activity. A modified most probable number (MPN) method was used to determine quantitative shifts in heterotrophic and phenanthrene degrader communities. During the first 4 to 6 d of treatment, heterotrophic populations increased in all amended soils. Both root debris-amended and exudate-amended soil then maintained larger phenanthrene degrader populations than in control soils later in the experiment after much of the phenanthrene had been utilized. Thus, root amendments had a greater impact over time on phenanthrene degraders than heterotrophs resulting in selective maintenance of degrader populations in amended soils compared with controls.

Avena↗
PubMed2005

Food packaging regulation in the United States and the European Union.

The regulation of food packaging has, indeed, become a global subject as the world's commercial channels have broadened since World War II. The first comprehensive regulatory statute governing the area was the Food Additives Amendment of 1958 in the United States, a modification of the 1938 Federal Food, Drug, and Cosmetic Act. Germany, Italy, The Netherlands, and Belgium began regulatory activity in the early 1960s and the European Community set in motion its own work in this direction beginning in 1976. Companies in the United States and the Europe have been struggling with each of the laws since then. The regulatory systems employed on the two continents are superficially similar but this is far from the truth in actual practice. Each has its own special history and set of exemptions; they vary tremendously. Each has its cadre of supporters as well but a considerable lack of understanding afflicts regulators and the regulated on both sides of the Atlantic. This three part report first discusses the history of the United States system and its characteristics; Book II covers the history of European Union regulations and their salient features; and Book III highlights the commonalities and differences in the systems, discusses their scientific basing points, and makes some recommendations as to how they can be brought closer together in the interests of harmonization and the removal of unnecessary trade barriers.

European Union↗
PubMed2006

Degradation kinetics of manure-derived sulfadimethoxine in amended soil.

Spreading of contaminated manure into agricultural lands as fertilizer is one of the major routes through which veterinary antibiotics enter the environment. In this study, the degradation of manure-derived sulfadimethoxine, a widely used veterinary sulfonamide antibiotic, in manure-amended soil was investigated. A kinetic model, called the availability-adjusted first-order model based on the first-order kinetics and an assumption of the availability of target compound during the degradation process, was developed and was found to fit sulfadimethoxine degradation well. The effect of initial sulfadimethoxine concentration showed that the degradation rate constant increased with decreasing initial concentration, indicating that the bioactivity of the degrading microorganisms in manure-amended soil was sensitive to sulfadimethoxine concentration. Sulfadimethoxine degradation was accelerated with increasing manure content in amended soil. Degradation in nonamended soil was significantly slower than in manure-amended soil. This indicated that sulfadimethoxine may become more persistent once it reaches soil after leaching from manure and that storage of manure for a certain period before application is needed to diminish sulfadimethoxine contamination. Sulfadimethoxine degradation was effectively enhanced with increasing moisture of amended soil. No adverse effect was observed with manure storage on the degradation of manure-derived sulfadimethoxine in amended soil.

Kinetics↗
PubMed2006

Phosphorus amendment reduces hepatic and renal oxidative stress in mallards ingesting lead-contaminated sediments.

Lead poisoning of waterfowl has been reported for decades in the Coeur d'Alene River Basin (CDARB) in Idaho as a result of the ingestion of lead-contaminated sediments. This study was conducted to determine whether the addition of phosphoric acid to CDARB sediments would reduce the bioavailability and toxicity of lead to the liver and kidney of mallards (Anas platyrhynchos). Mallards received diets containing 12% clean sediment (controls) or 12% sediment from three different CDARB sites containing 4520, 5390, or 6990 microg/g lead (dry weight) with or without phosphoric acid amendment. Liver and kidney lead concentrations were significantly higher in all CDARB treatment groups and ranged from geometric mean values of 18.2 (liver) and 28.7 (kidney) for the first 2 sites to 22.5 (liver) and 45.6 (kidney) microg/g (wet weight) for the third site. With amendments all liver lead concentrations were reduced 36 to 55%, and all kidney lead concentrations were lowered 54 to 73%. Unamended CDARB sediment from the third site resulted in the following hepatic effects: over 1.6-fold elevation of liver glutathione (reduced form; GSH) concentration, higher GSH S-transferase and oxidized glutathione (GSSG) reductase activities, and lower protein-bound thiols (PBSH) concentration. Renal effects included higher kidney GSH concentrations for all CDARB sites, with over 2.1-fold higher for the third site. Resulting kidney GSSG to GSH ratios were lower at two sites. At the third site, gamma-glutamyl transferase (GGT) activity was elevated, and lipid peroxidation as thiobarbituric acid-reactive substances (TBARS) was 1.7-fold greater. Amendment restored all hepatic variables as well as the renal variables TBARS and GGT so they did not differ from controls. Although amendments of phosphorus substantially reduced the bioavailability of lead and some of the adverse effects, lead concentrations in the tissues of mallards fed the amended sediments were still above those considered to be harmful to waterfowl under the present conditions.

Animal Feed↗
PubMed1993

A phase I trial of ifosfamide, mesna, and cisplatin in advanced non-small cell lung cancer. A cancer and leukemia group B study.

BACKGROUND: This Phase I study was designed to determine the maximum tolerated dose of ifosfamide-mesna with a fixed dose of cisplatin without growth factor or hematopoietic precursor support. METHODS: Twenty-five patients with previously untreated advanced non-small cell lung cancer were treated at four dose levels. Initially, the cisplatin dose was 100 mg/m2 given on day 1. Seven patients were treated with ifosfamide 2.0 g/m2 days 1 to 3, and six patients received ifosfamide 2.5 g/m2 days 1 to 3. Mesna was given at 20% of the ifosfamide dose at 0, 4, and 6 hours after ifosfamide. Cycles were repeated every 4 weeks. RESULTS: Dose-limiting toxicities (myelosuppression and renal toxicity) were seen at dose level 2 (ifosfamide 2.5 g/m2). Because 5 of the first 13 patients experienced Grade 3 renal toxicity, the study was amended to give cisplatin in divided doses. An additional six patients each were treated at dose level 3 (ifosfamide 2.0 g/m2 days 1-3) and dose level 4 (ifosfamide 2.5 g/m2 days 1-3) with cisplatin 33 mg/m2 days 1 to 3. Dose-limiting toxicity (myelosuppression) was reached at ifosfamide 2.5 g/m2. No further Grade 3 renal toxicity was seen. Grade 3 or worse toxicities were seen as follows: neutropenia 80%, thrombocytopenia 48%, nausea/vomiting 36%, anemia 32%, renal 20%, central nervous system 16%, and infection 16%. Two toxic deaths occurred, both with infection, renal failure, and neutropenia. Partial responses were seen in 8 of 25 eligible patients (32%). CONCLUSIONS: The maximum tolerated dose in this group of patients was defined as ifosfamide 2.0 g/m2 days 1 to 3 when given with cisplatin 33 mg/m2 days 1 to 3. When combining high-dose cisplatin with ifosfamide, it is advisable to give cisplatin in divided doses.

Adult↗
PubMedDate not supplied

Hay-scented fern (Dennstaedtia punctilobula (Michx.) Moore) interference with growth of northern red oak (Quercus rubra L.) seedlings.

We assessed the impacts of hay-scented fern (Dennstaedtia punctilobula (Michx.) Moore) and subsoil liming (CaO amendments) on root and shoot growth of greenhouse-grown, first-year, northern red oak (Quercus rubra L.) seedlings. Red oak seedlings and ferns were grown in reconstructed soil profiles of four common Pennsylvanian forest soils. When grown in the presence of hay-scented ferns, with or without subsoil liming, red oak seedlings had significantly reduced height growth, and foliar, stem and total root biomass. Fern foliar biomass was significantly reduced when ferns were grown with red oaks, but there was no significant difference in total belowground biomass of ferns. Belowground fern biomass was concentrated in the upper soil profile, whereas red oak roots showed a variety of distributions. In the presence of ferns, fine root branching in red oak was reduced in the organic horizons of three of the four soils tested. In both the presence and absence of ferns, root branching in red oak was also significantly and negatively correlated with the concentration of 0.01 M SrCl(2)-extractable aluminum in the mineral horizons (r(2) = 0.77). Subsoil liming generally improved root branching in red oaks. The presence of ferns significantly reduced ectomycorrhizal infection frequency in red oak. We conclude that hay-scented fern inhibited root branching and suppressed above- and belowground biomass accumulation of first-year northern red oak seedlings.

Journal Article↗
PubMedDate not supplied

Dissolved organic carbon dynamics in a riparian aquifer: effects of hydrology and nitrate enrichment.

The capacity of riparian soils to remove nitrate (NO3) from ground water is well established, but the effects of ground water NO3(-)-enrichment on C dynamics are not well studied. We incubated horizontal cores of aquifer material extracted from beneath moderately well-drained (MWD) and poorly drained (PD) soils in a riparian forest in Rhode Island, USA for 132 d, and dosed (flow rate, 170 mL d(-1); dissolved O2, 2 in PD and 5 mg L(-1) in MWD cores) with ground water amended with either Br-, Br(-)+ NO3- (10 mg N L(-1)), or Br(-) + NO3(-) + DOC (20 mg C L(-1)). The DOC was extracted from forest floor material and added during the first 56 d of the experiment. Addition of NO3- had limited effect on CO2 production while DOC amendment had a significant effect in the PD but not in the MWD mesocosms. Total CO2 production (mg CO2-C kg(-1) soil) was 6.3, 7.0, and 10.1 in the PD and 3.6, 4.0, and 4.5 in the MWD cores amended with Br-, Br(-) + NO3-, and Br(-) + NO3(-) + DOC, respectively. Carbon balance (C(bal) = DOC(in) - (DOC(out) + CO2-C) showed a net C retention of 8.0 mg C kg(-1) soil in the DOC-amended MWD cores (equivalent to 50% of the DOC added), and a net C loss of 8.3 mg C kg(-1) soil in similarly treated PD cores. The lack of C retention in the PD cores was ascribed to reductive dissolution of minerals implicated in DOC sorption. These findings underscore that there is marked variation in C dynamics in riparian aquifers that has the potential to influence the fate of NO3- and DOC in the landscape.

Carbon↗
PubMed1987

Ecology of Indigenous Soil Rhizobia: Response of Bradyrhizobium japonicum to Readily Available Substrates.

Populations of indigenous Bradyrhizobium japonicum serocluster 123 and serogroups 110 and 138 were studied after various sugars were added to their soil habitat. Loam soil with approximately 10 cells of each group per g of soil were amended every 3 days with 0.1% glucose, sucrose, arabinose, xylose, or galactose. Enumerations of the populations were made every 12 days by immunofluorescence assay. Each B. japonicum population in the sugar-treated soils increased by about 1 log during the first 12 days, to a maximum of about 10 cells by day 36 or 48, irrespective of the sugar added. Maximum growth rates were similar for each group and occurred during the 12-day incubation period. The most rapid growth was in response to arabinose, with a mean generation time of about 3.0 days. Other mean doubling times were 4.0 days with glucose and galactose treatments, 4.5 days with xylose treatment, and 5.4 days with sucrose amendment. These data provide the first direct evidence that indigenous soil rhizobia can compete successfully with other soil bacteria for readily available substrates in soil in the absence of host legume roots or other rhizospheres. The growth rates in soil of the specific B. japonicum populations studied were nearly the same with a given sugar treatment but varied considerably with different sugars. The mean generation times of 3 to 5 days are among the first reported growth rates for heterotrophic bacteria in natural soil.

Journal Article↗
PubMed2006

Stem cell transplantation: potential impact on heart failure.

Cell transplantation is a promising new modality in treating damaged myocardium after myocardial infarction and in preventing postmyocardial infarction LV remodelling. Two strategies are plausible: the first uses adult tissue stem cells to replace the scar tissues and amend the lost myocardium, whilst the second strategy uses embryonic stem cells in an attempt to regenerate myocardium and/or blood vessels.

Adult Stem Cells↗
PubMed2003

Altretamine (hexamethylmelamine) in the treatment of platinum-resistant ovarian cancer: a phase II study.

OBJECTIVE: To evaluate the activity of oral Altretamine in women with epithelial ovarian carcinoma who responded (PR or CR) to first line chemotherapy but relapsed within 6 months. The protocol was later amended to include patients with relapse within 12 months. METHODS: A multicentric phase II trial. The patients had to have measurable disease. No more than one prior chemotherapy regiment was allowed. The patients were treated with 260 mg/m(2)/day of Altretamine in four divided doses for 2 weeks, repeated every 4 weeks. The response was evaluated after every two courses. RESULTS: Thirty-one eligible patients were treated with a median of 3 courses of Altretamine (range 1-12). Hematological toxicity was minimal. Gastrointestinal toxicity was common. Response evaluation was possible for 26 patients. Three patients (9.7% intent-to-treat) achieved a partial response. Eight patients had stable disease, and 15 patients had progressive disease after two treatment courses. The median time to progression was 10 weeks (range, 5-51 weeks). Medial survival was 34 weeks (range, 7-112+). CONCLUSION: Altretamine should not be chosen as standard treatment in patients with platinum-resistant recurrent ovarian cancer. However, Altretamine represents a useful alternative in patients who prefer oral treatment or when socioeconomic considerations are an important issue.

Administration, Oral↗
PubMed2004

Impact of virioplankton on archaeal and bacterial community richness as assessed in seawater batch cultures.

During cruises in the tropical Atlantic Ocean (January to February 2000) and the southern North Sea (December 2000), experiments were conducted to monitor the impact of virioplankton on archaeal and bacterial community richness. Prokaryotic cells equivalent to 10 to 100% of the in situ abundance were inoculated into virus-free seawater, and viruses equivalent to 35 to 360% of the in situ abundance were added. Batch cultures with microwave-inactivated viruses and without viruses served as controls. The apparent richness of archaeal and bacterial communities was determined by terminal restriction fragment length polymorphism (T-RFLP) analysis of PCR-amplified 16S rRNA gene fragments. Although the estimated richness of the prokaryotic communities generally was greatly reduced within the first 24 h of incubation due to confinement, the effects of virus amendment were detected at the level of individual operational taxonomic units (OTUs) in the T-RFLP patterns of both groups, Archaea and Bacteria. One group of OTUs was detected in the control samples but was absent from the virus-treated samples. This negative response of OTUs to virus amendment probably was caused by viral lysis. Additionally, we found OTUs not responding to the amendments, and several OTUs exhibited variable responses to the addition of inactive or active viruses. Therefore, we conclude that individual members of pelagic archaeal and bacterial communities can be differently affected by the presence of virioplankton.

Animals↗
PubMedDate not supplied

Fly ash as a liming material for cotton.

A field experiment was conducted to determine the effect of fly ash from a coal combustion electric power facility on soil acidity in a cotton (Gossypium hirsutum L.) field. Fresh fly ash was applied to a Bosket fine sandy loam (fine-loamy, mixed, thermic Mollic Hapludalf) soil with an initial soil pH(salt) of 4.8. The fly ash was equivalent to 42 g kg(-1) calcium carbonate with 97% passing through a 60 mesh (U.S. standard) sieve. Fly ash was applied one day before cotton planting in 1999 at 0, 3.4, 6.7, and 10.1 Mg ha(-1). No fly ash was applied in 2000. Within 60 d of fly ash application in 1999, all rates of fly ash significantly increased soil pH above 6.0. Manganese levels in cotton petioles were reduced significantly by 6.7 and 10.1 Mg ha(-1) of fly ash. Soil boron (B) and sodium (Na) concentrations were significantly increased with fly ash. In 1999, B in cotton leaves ranged from 72 to 84 mg kg(-1) in plots with fly ash applications. However, no visual symptoms of B toxicity in plants were observed. In 1999, cotton lint yield decreased on average 12 kg ha(-1) for each Mg of fly ash applied. In 2000, cotton yields were significantly greater for the residual 3.4 and 6.7 Mg fly ash ha(-1) plots than the untreated check. Due to the adverse yield effects measured in the first year following application, fly ash would not be a suitable soil amendment for cotton on this soil at this time.

Boron↗