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PubMed1987

A first step quantification by correlation techniques of the variability in some time intervals measured on the Politecnico/Ca' Granda VCG Database On Young Normal Subjects.

The unevident variability during a 30-min period on intervals measured once every cardiac cycle was investigated by correlation techniques implemented on a digital computer, on normal healthy subjects from the "Politecnico/Ca' Granda VCG Database On Young Normal Subjects". Our most important conclusions are as follows: Generally each time series, related to the many interval values measured, shows that its variability is different from that of the R-R intervals. In particular Bazzett's formula, which provides the widely used "corrected QT interval", has to be amended.

Algorithms↗

PubMed1997

Anaerobic aquifer transformations of 2,4-dinitrophenol under different terminal electron accepting conditions.

We evaluated the susceptibility of 2,4-dinitrophenol (2,4-DNP) and 2,4-diaminophenol to anaerobic biodegradation in aquifer slurries. Aquifer microorganisms depleted 2,4-DNP at rates of 25, 9 and 0.4 microM/day under methanogenic, sulfate-reducing and nitrate-reducing conditions, respectively. Rates of abiotic, 2,4-DNP loss in autoclaved control incubations were 7.2, 6.2 and 0.95 microM/day respectively. Abiotic, 2,4-DNP reduction was especially important as the first step in its transformation. 2-Amino-4-nitrophenol was produced by this process, but this compound was further metabolized in methanogenic and sulfate-reducing aquifer slurries. This partially reduced compound persisted in autoclaved controls and in the nitrate-reducing aquifer slurries. Aquifer slurries incubated with either 2,4-DNP or 2,4-diaminophenol produced methane when incubated with no other electron acceptor suggesting that mineralization had occurred under these conditions. In parallel experiments, aquifer slurries amended with 2,6-dinitrophenol or picric acid did not produce methane at levels above the substrate unamended controls.

Journal Article↗

PubMed2001

Influence of thermal treatment on sequential extraction and leaching behaviour of trace metals in a contaminated sewage sludge.

The losses of weight and organic matter of a sludge caused by thermal treatments at 180 degrees C, 300 degrees C and 400 degrees C were determined in order to assess how the possibilities of sludge use were influenced. The sludge heated at 180 degrees C lost small amounts of weight and organic matter (9.8%) but the losses from the two other treatments were large enough (92.2% and 99.9% in organic matter) to preclude the use of the sludges as organic amendments. The concentration and potential lability and leachability of Cr, Cu, Fe, Mn, Ni, Pb and Zn in the native sludge and in the thermal-treated sludge samples were studied by means of a five-step chemical fractionation method and a column experiment. As a consequence of heating, the trace metals were more strongly fixed in the treated sludges, as could be seen by the decrease with temperature of the ratio between the sum of the first two sequential-extracted fractions and the residual fraction. The leaching results showed that, for the native sludge, the quantities of studied metals leached were larger than for the sludge heated to 180 degrees C. The order of leachability of metals was the same in both cases, and the same equation could be used to calculate the quantities of metals leached. The amounts of metals leached correlated significantly with the first extracted fraction (exchangeable metals) and an equation could be used to calculate the quantities leached, as a function of that fraction.

Hot Temperature↗

PubMed1996

Docetaxel in patients with metastatic breast cancer: a phase II study of the National Cancer Institute of Canada-Clinical Trials Group.

PURPOSE: The National Cancer Institute of Canada-Clinical Trials Group (NCIC-CTG) conducted a phase II study to assess the efficacy and toxicity of docetaxel as first-line chemotherapy in metastatic breast cancer (MBC). PATIENTS AND METHODS: Fifty-one patients with measurable MBC were studied. Three patients were ineligible and were excluded from analysis. The planned dose of docetaxel was 100 mg/m2 intravenously (i.v.) every 3 weeks. Prior adjuvant chemotherapy was allowed if at least 12 months had elapsed from completion of treatment to recurrence. RESULTS: The most severe toxicity was granulocytopenia. Ten patients (20.8%) were hospitalized for febrile neutropenia. The protocol was amended to a starting dose of 75 mg/m2 for the last 16 patients. Sixty percent of patients experienced hypersensitivity reactions (HSRs). After two protocol amendments, the use of a premedication regimen of oral dexamethasone and i.v. H1 and H2 blockers prevented significant HSRs. Edema developed in 62% of patients and was cumulative, was present in 50% who received greater than 400 mg/m2, and was not improved by premedication regimens. Following an independent radiology review, 22 partial remissions and four complete responses in 47 assessable patients were confirmed (response rate, 55%; 95% confidence interval [CI], 40% to 69%). The response rate for 15 assessable patients registered at 75 mg/m2 was 40% (95% CI, 16% to 67%); for 32 assessable patients registered at 100 mg/m2, the response rate was 63%, (95% CI, 43% to 78%). CONCLUSION: Docetaxel is an active agent in MBC. Its activity as a single agent is comparable to many combination chemotherapy regimens and is not affected by prior adjuvant chemotherapy. Studies are ongoing to improve its therapeutic index and to incorporate docetaxel in combination chemotherapy regimens.

Adult↗

PubMed1982

Refugee resettlement program and Cuban/Haitian entrant program: cash and medical assistance policies. Social Security Administration. Interim final rule.

This interim final regulation amends the refugee resettlement program regulations (45 CFR Part 400) and establishes new policies on cash and medical assistance available to refugees and Cuban and Haitian entrants who are ineligible for Aid to Families with Dependent Children (AFDC), Supplemental Security Income (SSI), adult assistance (OAA, AB, APTD, and AABD) in the Territories and medicaid. The Refugee Resettlement Program (RRP) provides Federal reimbursement to States for 100 percent of the costs of cash and medical assistance provided, during the first 36 months after entry into the United States, to such refugees in accordance with applicable program rules and requirements and the administrative costs of providing such assistance. Cash assistance provided to such refugees under the RRP is termed "refugee cash assistance" (RCA); and medical assistance provided to such refugees under the RRP is termed "refugee medical assistance" (RMA). This regulation permits 100 percent Federal reimbursement for RCA and RMA for an eligible refugee for the first 18 months that a refugee is in the United States. For a refugee who has been in the U.S. more than 18 months but less than 36 months, the regulation permits a State, at its option, to seek RRP reimbursement for the cost of General Assistance (GA) provided to such a refugee.

Cuba↗

PubMed2002

Accuracy of reporting endocervical component adequacy--a continuous quality improvement project.

Inaccurate reporting of the absence of an endocervical (EC) component on Pap smears often results in slide rescreens, amended reports, clinician dissatisfaction, and sometimes unnecessary repeat smears. Therefore, the accuracy of reporting EC component adequacy was selected as a quality indicator for the laboratory continuous quality improvement program (CQI). The process consisted of problem identification, analysis of the situation, collection of data, implementation of solutions, and evaluation of results. The objective of the study was to determine if the accuracy of reporting EC component adequacy on Pap smears improved after application of such a program. During the first phase, 150 Pap smears originally reported with the absence of an adequate EC component and 150 smears reported with the presence of an adequate EC component were rescreened to measure the baseline accuracy of EC component adequacy reporting. The improvement process was then implemented. A cause-and-effect diagram was developed and root cause was determined. A presentation was then made to the cytology staff. Criteria for EC component adequacy were reviewed, examples were shown, and standardized marking of EC component was implemented. Following improvement actions, a second audit of 150 Pap smears reported with the absence of an adequate EC component as well as 150 smears reported with the presence of an adequate EC component was undertaken to measure change in performance in assessing EC component adequacy. For the baseline rescreening, before initiation of the CQI program, 98% accuracy was achieved with smears that were reported as adequate for EC component present. However, the accuracy with smears reported as absence of an adequate EC component was only 71%, i.e., an adequate EC component was identified in almost 1/3 of these cases on rescreen. After the implementation of improvement actions, the accuracy with smears reported with the presence of EC component remained high (98%) and the accuracy of reporting the absence of EC component was 90%. The difference of the latter before and after the implementation was statistically significant (P = 0.015, z-test). The accuracy of reporting EC component adequacy increased following the CQI process. Using reporting EC component adequacy as an example, we demonstrate that by treating clinical problems as quality control issues and applying basic quality improvement tools, a positive outcome can be effected.

Cell Biology↗

PubMed1978

Effect of moisture level on nitrogen immobilization as affected by wheat straw decomposition in soil.

Samples of a slightly degraded chernozem soil were amended with 2 per cent of wheat straw at three moisture levels (10, 20, and 30 per cent) and were provided with 160, 240, and 400 ppm of ammoniacal nitrogen. Amounts of total, ammonia, and nitrate were determined at different periods of incubation at 28 degrees C and immobilization of the total available nitrogen in the soil was calculated. Substantial amounts of the added nitrogen were immobilized in the soil as a result of the straw decomposition during the first month of incubation. The amount of inorganic nitrogen (NH4 + -N + NO3 - -N), bound within 75 days of incubation, was almost three times less than that immobilized within 30 days. Maximum quantity of nitrogen was immobilized at 30 and 20 per cent moisture levels at 30 and 75 days of incubation, respectively. Minimum immobilization was observed at 10 per cent moisture at almost all levels of nitrogen. The absolute amount of nitrogen immobilized increased in proportion to the quantity of nitrogen added, but the relative immobilization tended to decrease with the increased inorganic nitrogen the soil.

Humidity↗

PubMed2003

An air quality data analysis system for interrelating effects, standards, and needed source reductions: Part 13--Applying the EPA Proposed Guidelines for Carcinogen Risk Assessment to a set of asbestos lung cancer mortality data.

The Clean Air Act Amendments of 1990 (CAAA-90) list 189 hazardous air pollutants (HAPs) for which "safe" ambient concentrations are to be determined. The primary purpose of this paper is to develop two mathematical models, lognormal and logarithmic, that effectively express excess lung cancer mortality as a function of asbestos concentration for an example set of data and also to suggest using these two models for additional HAPs. The secondary purpose of this paper is to calculate a "safe" asbestos concentration by first assuming a default linear extrapolation (to one excess death per million people, as specified for carcinogenic HAPs). The resulting "safe" concentration is an impossible-to-achieve 1/1000 of present background asbestos concentrations. A letter to the editor and a response in this Journal issue use additional asbestos data that suggest that the "safe" concentration should be about 730 times higher than first calculated here and that a default nonlinear extrapolation should be used instead, with the "safe" concentration proportional to the desired mortality level raised to the 0.39 power. These results suggest that the most important problem in setting a "safe" concentration for each carcinogenic HAP is to determine the correct nonlinear extrapolation to use for each HAP.

Asbestos↗

PubMed2004

Sources of variability on the estimate of treatment effect in the PROWESS trial: implications for the design and conduct of future studies in severe sepsis.

OBJECTIVE: To elucidate sources of variability in the estimate of treatment effects in a successful phase 3 trial in severe sepsis and to assess their implications on the design of future clinical trials. DESIGN: Retrospective evaluation of prospectively defined subgroups from a large phase 3, placebo-controlled clinical trial (PROWESS). SETTING: The study involved 164 medical centers. PATIENTS: Patients were 1,690 patients with severe sepsis. INTERVENTIONS: Drotrecogin alfa (activated) (Xigris) 24 microg/kg/hr for 96 hrs, or placebo. MEASUREMENTS AND MAIN RESULTS: All prospectively defined subgroups were examined to identify treatment effects that potentially differed across subgroup strata (assessed by Breslow-Day p < .10). Potential interactions were identified for subgroups defined by a) presence vs. absence of a significant protocol violation (p = .07); b) original vs. amended protocol (p = .08); and c) Acute Physiology and Chronic Health Evaluation (APACHE) II quartile at baseline (p = .09). No treatment benefit was observed in patients having a protocol violation, regardless of type. There appeared to be less treatment effect in patients enrolled under the original vs. amended protocol. The risk ratio exceeded 1.0 for patients in the lowest APACHE II score quartile. A highly significant correlation was observed between the sequence of enrollment at a site, the frequency of protocol violations, and the observed treatment effect. As enrollment increased, frequency of protocol violations decreased (p < .0001) and the treatment effect improved. The correlation between the sequence of enrollment and improvement in treatment effect remained even after removal of patients with protocol violations. Removal of the first block of patients at each site from the analysis reduced the extent of interaction by protocol version and APACHE II score. CONCLUSIONS: A learning curve appeared to be present within the PROWESS trial such that the ability to demonstrate efficacy improved with increasing site experience. This potential learning curve may have implications for design of future trials. Investigational sites may need to require a minimum level of protocol-specific experience to appropriately implement a given trial. This experience should be an important consideration in designing trials and analysis plans. Diligence by coordinating centers, site investigators, study coordinators, and sponsors is necessary to ensure that the protocol is executed as designed such that a treatment benefit, if present, will be evident.

APACHE↗

PubMed1982

Interactions of bacterial and amoebal populations in soil microcosms with fluctuating moisture content.

Sterilized soil samples (20 g of soil per 50-ml flask), amended with 600 mug of glucose-carbon and 60 mug of NH(4)-N . g of dry soil, were inoculated with bacteria (Pseudomonas paucimobilis) alone or with bacteria and amoebae (Acanthamoeba polyphaga). We used wet-dry treatments, which involved air drying the samples to a moisture content of approximately 2% and remoistening the samples three times during the 83-day experiment. Control treatments were kept moist. In the absence of amoebae, bacterial populations were reduced by the first drying to about 60% of the moist control populations, but the third drying had no such effect. With amoebae present, bacterial numbers were not significantly affected by the dryings. Amoebal grazing reduced bacterial populations to 20 to 25% of the ungrazed bacterial populations in both moisture treatments. Encystment was an efficient survival mechanism for amoebae subjected to wet-dry cycles. The amoebal population was entirely encysted in dry soil, but the total number of amoebae was not affected by the three dryings. Growth efficiencies for amoebae feeding on bacteria were 0.33 and 0.39 for wet-dry and constantly moist treatments, respectively, results that compared well with those previously reported for Acanthamoeba spp.

Journal Article↗

PubMed1995

Criteria for investigation of the product equivalence of monoclonal antibodies for therapeutic and in vivo-diagnostic use in case of introduction of changes in the manufacturing process.

The development of a monoclonal antibody for therapeutic or in vivo-diagnostic use from the first description to clinical trials and compilation of the dossier for granting the license requires a time consuming and expensive program. Due to its long development time, a particular monoclonal antibody can be subjected to a series of changes and improvements in manufacturing technology before licensure. In addition, the application for marketing authorization of biotechnology-derived medicinal products is not to be considered as an endpoint of a drawn-out development process which ends with license, because changes, amendments or improvements of the manufacturing process occur after a marketing authorization for a monoclonal antibody has been granted. Most of these changes, even minor qualitative and quantitative changes in the active substance itself, would require a new application according to the legal regulations of the European Union and of the national drug laws of the Member States. The paper proposes a procedure to take previously evaluated development-related data into account by evaluation of the product equivalence of both antibody forms ascertained before and after introduction of changes in the manufacturing process. The thorough in vitro analysis of parameters such as isotype, subclass, affinity, microheterogeneity, molecular weight, primary and secondary structure, structural integrity of the antibody molecule, glycosylation pattern, specificity, cross-reactivity and biological potency with subsequently performed pharmacological/toxicological evaluation of biodistribution, half life and safety provide sufficient data for decision on the need for further clinical trials.

Animals↗

PubMed2005

Soil-solution speciation of Cd as affected by soil characteristics in unpolluted and polluted soils.

Total metal content by itself is insufficient as a measure to indicate actual environmental risk. Understanding the mobility of heavy metals in the soil and their speciation in the soil solution is of great importance for accurately assessing environmental risks posed by these metals. In a first explorative study, the effects of general soil characteristics on Cd mobility were evaluated and expressed in the form of empirical formulations. The most important factors influencing mobility of Cd proved to be pH and total soil content. This may indicate that current legislation expressing the requirement for soil sanitation in Flanders (Belgium) as a function of total soil content, organic matter, and clay does not successfully reflect actual risks. Current legal frameworks focusing on total content, therefore, should be amended with criteria that are indicative of metal mobility and availability and are based on physicochemical soil properties. In addition, soil-solution speciation was performed using two independent software packages (Visual Minteq 2.23 and Windermere Humic Aqueous model VI [WHAM VI]). Both programs largely were in agreement in concern to Cd speciation in all 29 soils under study. Depending on soil type, free ion and the organically complexed forms were the most abundant species. Additional inorganic soluble species were sulfates and chlorides. Minor species in solution were in the form of nitrates, hydroxides, and carbonates, the relative importance of which was deemed insignificant in comparison to the four major species.

Belgium↗

PubMed2006

Draft EU regulation on paediatric medicines: some improvements but still far from perfect.

(1) In 2004, the European Commission proposed a draft European Regulation on paediatric medicines. This draft was more closely oriented towards defending drug companies' interests than with meeting children's medical needs. (2) Despite pressure from drug companies and their allies, several major improvements were made to the draft at its first reading in the European Parliament, thanks especially to the efforts of the Medicines in Europe Forum. (3) In particular, European deputies pushed for a better definition of children's needs and paediatric research priorities, greater transparency at various important stages of the market authorization procedure, and strengthened pharmacovigilance. (4) Yet the incentives and rewards offered to companies fail to take into account the notion of true therapeutic advantages and R&D expenditure. (5) Unfortunately the Commission refused some important amendments and published a new draft proposal, which was accepted by the Council of Health Ministers at the end of 2005. The new draft will come before the Parliament for a second reading in 2006.

Child↗

PubMedDate not supplied

In situ reduction of chromium(VI) in heavily contaminated soils through organic carbon amendment.

Chromium has become an important soil contaminant at many sites, and facilitating in situ reduction of toxic Cr(VI) to nontoxic Cr(III) is becoming an attractive remediation strategy. Acceleration of Cr(VI) reduction in soils by addition of organic carbon was tested in columns pretreated with solutions containing 1000 and 10 000 mg L(-1) Cr(VI) to evaluate potential in situ remediation of highly contaminated soils. Solutions containing 0,800, or 4000 mg L(-1) organic carbon in the form of tryptic soy broth or lactate were diffused into the Cr(VI)-contaminated soils. Changes in Cr oxidation state were monitored through periodic micro-XANES analyses of soil columns. Effective first-order reduction rate constants ranged from 1.4 x 10(-8) to 1.5 x 10(-7) s(-1), with higher values obtained for lower levels of initial Cr(VI) and higher levels of organic carbon. Comparisons with sterile soils showed that microbially dependent processes were largely responsible for Cr(VI) reduction, except in the soils initially exposed to 10 000 mg L(-1) Cr(VI) solutions that receive little (800 mg L(-1)) or no organic carbon. However, the microbial populations (< or = 2.1 x 10(5) g(-1)) in the viable soils are probably too low for direct enzymatic Cr(VI) reduction to be important. Thus, synergistic effects sustained in whole soil systems may have accounted for most of the observed reduction. These results show that acceleration of in situ Cr(VI) reduction with addition of organic carbon is possible in even heavily contaminated soils and suggest that microbially dependent reduction pathways can be dominant.

Bacteria↗

PubMed1999

Antiphospholipid antibody syndrome in renal transplantation: occurrence of clinical events in 96 consecutive patients with systemic lupus erythematosus.

We report the results of a detailed examination of clinical events associated with the antiphospholipid antibody (aPL) syndrome in 96 consecutive patients with systemic lupus erythematosus (SLE) who underwent renal transplantation between January 1, 1984, and September 1, 1996. Because of the retrospective nature of our study, we developed strict definitions of clinical events considered to be associated with the aPL syndrome. We reviewed all available hospital, clinic, and outside records of the patients with SLE who underwent transplantation at our center during this time period and noted the results of three standard serological tests for aPLs, when available. Mean follow-up of the 96 patients was 62.6 months. Eighty-five of the 96 patients (88.5%) had at least one test for aPLs performed, and 25 patients (29.4%) had at least one abnormal test result. Among these 25 patients, 15 patients (60%) had clinical events associated with aPL syndrome. Ten patients (10.4%) either died of the aPL syndrome or had an aPL-associated clinical event within 3 months of transplantation. Other morbidity from the aPL syndrome in these 15 patients included: thrombotic arteriolar microangiopathy (2 patients), stroke (4 patients), ocular ischemia (7 patients), deep vein thrombosis or pulmonary embolism (6 patients), renal artery or vein thrombosis (4 patients), peripheral ischemia (1 patient), and fetal wastage (3 patients). By comparison, among the 60 patients with normal aPL test results, only 5 patients had clinical events compatible with the aPL syndrome (P < 0.0001 by chi-squared test). aPLs may be associated with significant morbidity and mortality in patients with SLE undergoing renal transplantation. This study is the first attempt to quantify the impact of aPLs on renal transplantation in a large population of patients with SLE. Further investigation of aPLs in SLE patients with end-stage renal disease is required to clarify the risks, benefits, and optimal clinical management of renal transplantation for these patients.

Antiphospholipid Syndrome↗

PubMed1988

Seventeen years of legalized abortion in Singapore.

"In this paper we first discuss the two-stage process of legalizing induced abortion in Singapore, the initial legalization to make it available on a restrictive basis in 1970 and the complete liberalization to make it available on demand from 1975 onwards. The incidence of abortions registered in the last seventeen years and the major characteristics of aborters are analysed. The impact of abortion on the rapid decline of fertility to below-replacement level is highlighted, and the need to reduce abortion by amending the more liberal aspects of the law are considered at the end of the paper."

Abortion, Induced↗

PubMed2005

[Recording and reporting adverse reactions in clinical trials. New legal provisions according to the 12th Law Amending the German Drug Law (AMG) and the Ordinance on GCP (GCP-V)].

With the 12th Law Amending the German Drug Law and the Ordinance on GCP (GCPV), new legal provisions for clinical trials came into force in August 2004. These include specific definitions and differentiated reporting obligations affecting investigators, sponsors, authorities and ethics committees concerning pharmacovigilance in clinical trials. The definitions according to section sign3 (6-8) GCP-V make clear that these provisions focus on those adverse events and adverse drug reactions, which are related to investigational medicinal products. In the GCP-V for the first time legally binding provisions for investigators are laid down defining obligations to report all serious adverse events to the sponsor. The sponsor of clinical trials plays a decisive role concerning the evaluation, documentation and reporting to the competent higher authorities, ethics committees and investigators involved in the clinical trial. In the GCP-V different time limits concerning the reporting for sponsors are laid down. The requirements concerning expedited reporting focus on suspected unexpected serious adverse reactions (SUSARs), i. e. those adverse serious reactions, which are not described in the information on the investigational medicinal product. The time limit for reporting SUSARs leading to death or life-threatening SUSARs is 7 days, while for other SUSARs the time limit is 15 days. Besides the responsibilities on expedited reporting the sponsor has to submit a line listing of all serious adverse reactions which occurred during the clinical trial and a report on the safety of the trial subjects on an annual basis or on request. On the European level the harmonisation concerning the provisions on pharmacovigilance in clinical trials according to the Directive 2001/20/EC and the Eudravigilance database should contribute to reach a faster and more effective exchange of safety information related to clinical trials between the different competent authorities of the EU member states.

Adverse Drug Reaction Reporting Systems↗

PubMed2006

Changing chemical composition of precipitation in Wilmington, North Carolina, U.S.A.: implications for the Continental U.S.A.

The H+(aq) concentration in Wilmington, NC, precipitation has decreased by approximately 50% during the preceding two decades, similar to trends seen nationwide. The decrease in acidity is important because solution pH plays a key role in atmospheric reactions, and because the change is so large. This study presents the first long-range study of dissolved organic carbon (DOC) levels in precipitation which demonstrates that DOC concentrations have decreased by approximately half in Wilmington, NC, precipitation. The concentrations of H+(aq) and DOC are highly correlated primarily because small organic acids contribute to both DOC and H+(aq) in precipitation. Ammonium ion concentrations in precipitation have increased due to increased agricultural activities, and this also affects precipitation pH. The reduction of SO2 emissions in 1995 imposed by the Clean Air Act Amendment, better control of emissions of volatile organic compounds, and the increase in ammonia emissions all contribute to the decreasing H+(aq) in precipitation nationwide. These compositional changes in precipitation have many environmental implications, such as decreased acid deposition to lakes, changing speciation for trace metals in precipitation, increased ammonium deposition to coastal waters, and decreased DOC transport to the open ocean.

Acid Rain↗