bluuebunny/crossref_metadata_2025 huggingface dataset:
Antimicrobial Activity of Tigecycline (GAR‐936) Against Enterococcus faecium and Staphylococcus aureus Used Alone and in Combination
Authors: Mercier Renee‐Claude , Kennedy Christine , Meadows Christina
Published: June 2004

Study Objective. To evaluate the antimicrobial properties of tigecycline, both alone and in combination with other antibiotics, against multidrug‐resistant strains of Enterococcus faecium and Staphylococcus aureus.

Design. In vitro study.

Setting. University laboratory.

Measurements and Main Results. Tigecycline, both alone and in combination with other antimicrobial agents, was evaluated against two strains of vancomycin‐resistant E. faecium (VREF), three glycopeptide‐intermediately resistant S. aureus strains, and one methicillin‐resistant S. aureus strain. Tigecycline's activity was compared with that of vancomycin, gentamicin, rifampin, and doxycycline, using time‐kill studies and analysis of minimum inhibitory concentrations and minimum bactericidal concentrations. Tigecycline also was evaluated in combination with vancomycin, gentamicin, rifampin, and doxycycline in time‐kill studies. The number of log10 colony‐forming units/ml at 24 hours was compared among treatment groups and growth control by analysis of variance. All isolates were susceptible to tigecycline, regardless of their susceptibilities to vancomycin or doxycycline. In time‐kill studies, tigecycline significantly inhibited the bacterial inoculum of all isolates (p<0.05). Although none of the tigecycline combinations studied had enhanced killing activity against VREF, when gentamicin was combined with tigecycline, improved effects were found against both strains. Against three of the S. aureus strains tested, the combination of gentamicin and tigecycline demonstrated enhanced or improved activity independently of each strain's susceptibility to gentamicin.

Conclusion. The multidrug‐resistant, gram‐positive bacteria tested, including doxycycline‐resistant isolates, were susceptible to tigecycline. The combination of tigecycline and gentamicin may have improved or enhanced activity against strains of vancomycin‐resistant enterococci and S. aureus.
Etiology and Frequency of Rhabdomyolysis
Authors: Black Corri , Jick Hershel
Published: June 2004

Study Objectives. To describe the etiology and characteristics of patients with clinically diagnosed rhabdomyolysis in the United Kingdom General Practice Research Database (GPRD), and to estimate the risk of rhabdomyolysis in general and that associated with lipid‐lowering agents in particular.

Design. Retrospective analysis.

Setting. The GPRD.

Patients. A base population of patients aged 20–75 years.

Intervention. Patients hospitalized with a computer‐recorded code for acute myositis or myoglobinuria, or with “rhabdo” recorded in free text comments were reviewed for evidence of rhabdomyolysis. Lipid‐lowering treatment among the base population also was calculated.

Measurements and Main Results. We identified 25 patients with rhabdomyolysis among 2.5 million in the base population between 1990 and 1999. Seven cases (28%) occurred after a drug overdose and 5 (20%) after septicemia. Among the 2935 concurrent users of statin and fibrate agents, one developed rhabdomyolysis.

Conclusion. Only 25 patients out of 2.5 million were found to have rhabdomyolysis. Of those, only one patient was taking a statin and fibrate concurrently, out of almost 3000 concurrent users. The free‐text comments field in the GPRD helped to identify patients with rhabdomyolysis.
Comparison of Gemfibrozil and Fenofibrate in Patients with Dyslipidemic Coronary Heart Disease
Authors: Packard Kathleen A. , Backes James M. , Lenz Thomas L. , Wurdeman Richard L. , Destache Christopher J. , Hilleman Daniel E.
Published: June 2004

Study Objective. To compare the lipid‐lowering effects of gemfibrozil and fenofibrate in patients with dyslipidemic coronary heart disease.

Design. Open label, fixed‐dosage, retrospective‐prospective, one‐way crossover from gemfibrozil to fenofibrate.

Setting. University‐affiliated outpatient clinics.

Patients. Eighty patients with coronary heart disease with a baseline low‐density lipoprotein cholesterol (LDL) level above 130 mg/dl or a triglyceride level of 200 mg/dl or higher who had been receiving gemfibrozil 600 mg twice/day Thirty‐nine (49%) patients had received concomitant therapy with a 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitor (statin) for a minimum of 9 months.

Intervention. All patients received gemfibrozil 600 mg twice/day for at least 3 months before being switched to fenofibrate 201 mg/day. Patients receiving concomitant statin therapy before crossover continued the statin at the same dosage after crossover. Before crossover, a fasting lipid profile was determined and patients were queried about the side effects of lipid‐lowering therapy. A repeat fasting lipid profile was obtained 12 weeks after the crossover.

Measurements and Main Results. Patients were stratified into those receiving versus those not receiving concomitant statin therapy. In both of these groups, fenofibrate was associated with significantly greater reductions in total cholesterol, LDL, and triglycerides than gemfibrozil (all p<0.001). In addition, fenofibrate was associated with a significantly greater increase in high‐density lipoprotein cholesterol (HDL) than gemfibrozil (p<0.001). No patients reported new‐onset adverse effects after the crossover.

Conclusions. Compared with gemfibrozil, fenofibrate produced significantly greater reductions in total cholesterol, LDL, and triglycerides and significantly greater increases in HDL. These changes were evident in patients receiving and not receiving concomitant statin therapy.
Implications of Amyloid Precursor Protein and Subsequent β‐Amyloid Production to the Pharmacotherapy of Alzheimer's Disease
Authors: Rojas‐Fernandez Carlos H. , Chen Ming , Fernandez Hugo L.
Published: June 2004

Alzheimer's disease is the most common type of dementia in older people. It is highly prevalent, affecting 35–45% of those aged 85 years or older. This disease has devastating consequences to patients, their families, caregivers, and the health care system. Much has been learned about its pathobiology, which has led to the β‐amyloid (Aβ) hypothesis. This hypothesis continues to be the predominant postulate of the pathobiology of Alzheimer's disease. Under this hypothesis, abnormal accumulation of Aβ is followed by a cascade of neurotoxic effects, which eventually result in neurodegeneration and development of Alzheimer's disease. This is thought to be the result of altered processing of the amyloid precursor protein (APP), preferentially by β‐ and γ‐secretase enzymes rather than nonamyloidogenic processing by α‐secretase. The growing body of knowledge regarding the processing of APP to various forms of Aβ has resulted in new approaches to the investigation of putative anti‐Alzheimer's disease compounds, including immune‐based therapies and various agents that can positively affect APP processing.
Prevention of Venous Thromboembolism in Acute Medical Illness
Authors: Enders Jason M. , Burke John M. , Dobesh Paul P.
Published: June 2004

Each year millions of patients experience a venous thromboembolic event. Due to the significant morbidity and mortality associated with venous thromboembolism (VTE), prevention is critical. Several groups, such as those undergoing orthopedic or general surgery, and patients experiencing acute myocardial infarction, are known to be at high risk for VTE. General medical patients—the medically ill—are also at risk, but they receive insufficient prophylaxis, which may be due to underestimation or lack of assessment of their risk. The American College of Chest Physicians recommends either unfractionated heparin or low‐molecular‐weight heparin to prevent VTE in these patients. The different pharmacologic profiles and dosing methods of these two groups of agents suggest that efficacy and safety may not be equivalent. Due to heterogeneity of medically ill patients and variability in clinical trials, a detailed review of the literature was performed to assist clinicians in assessing risk and choice of a regimen to prevent VTE.
National Survey of Pharmacist Certified Diabetes Educators
Authors: Shane‐McWhorter Laura , Fermo Joli D. , Bultemeier Nanette C. , Oderda Gary M.
Published: June 2004

We sought to determine the demographics of pharmacists who were certified diabetes educators (CDEs) and information about their training, professional affiliations, and types of diabetes education services that they provide. We also queried these pharmacists about clinical activities, reimbursement, impact of certification, and intent to pursue CDE recertification. A list of pharmacists who were CDEs as of August 31, 2000, was obtained from the National Certification Board for Diabetes Educators. We then sent a six‐page anonymous survey to 415 pharmacist CDEs; 233 surveys (56.1%) were returned. Of these respondents, 140 are women and 93 are men, with a mean age of 41.5 years. Most reside in Southern or Western states. Average time since pharmacist licensure was 17 years, and average time as a CDE was 5 years. Most had completed postgraduate training, including residencies and/or fellowships; 52.8% had faculty appointments; 46.7% stated they were billing for their services; and 45.9% were obtaining reimbursement. Most pharmacists (84.4%) stated that they intended to pursue CDE recertification. Providing details about pharmacist CDEs and their clinical activities may motivate other pharmacists to pursue this credential. Pharmacists are often the most accessible of all health care providers, and earning the CDE credential may be an important contribution to diabetes care and education.
Health‐Related Quality of Life in Patients 7 Months After a Myocardial Infarction: Factors Affecting the Short Form‐12
Authors: McBurney Christopher R. , Eagle Kim A. , Kline‐Rogers Eva M. , Cooper Jeanna V. , Mani Obli C. M. , Smith Dean E. , Erickson Steven R.
Published: June 2004

We assessed patients' health‐related quality of life after myocardial infarction and identified related variables. Clinical data were obtained retrospectively from medical records of consecutive patients admitted to a Midwestern university‐affiliated medical center with diagnosis of myocardial infarction from July 1999–July 2000. Telephone interviews 7 months after discharge were made to administer the Short Form‐12 (SF‐12) and obtain patient, disease, drug, and intervention data. Complete information was obtained from 200 patients (mean age 63.4 ± 13.1 yrs, 68% men). The mean Physical Component Summary (PCS)‐12 score was 40.6 ± 12.0, and the mean Mental Component Summary (MCS)‐12 score was 52.1 ± 10.0. Based on univariate analyses, low PCS‐12 scores were associated with women; non‐Q‐wave infarctions; greater number of illnesses; history of myocardial infarction, chronic heart failure (CHF), transient ischemic attack (TIA), renal disease, peripheral vascular disease, or percutaneous coronary intervention (PCI); rehospitalization during the interim period; and unscheduled PCI since index myocardial infarction. Low MCS‐12 scores were associated with age below 65 years, low overall self‐reported drug therapy compliance, low self‐reported compliance with angiotensin‐converting enzyme inhibitor and lipid‐lowering therapy, no history of coronary artery bypass graft, and no stress test since index myocardial infarction. A multivariate regression model for PCS‐12 kept the following variables: greater number of illnesses, history of CHF or TIA, and rehospitalization since index myocardial infarction. The MCS‐12 model contained age below 65 years, low overall compliance, and low compliance with lipid‐lowering therapy. Further work is necessary to determine noncardiovascular predictors of quality of life and whether interventions for these patients will result in improved quality of life.
Modeling the Cost‐Effectiveness of a Smoking‐Cessation Program in a Community Pharmacy Practice
Authors: Tran Mongthuong T. , Holdford David A. , Kennedy Daniel T. , Small Ralph E.
Published: June 2004

Objectives. To describe some of the costs of providing a smoking‐cessation program in a community pharmacy practice, and to model the program's cost‐effectiveness compared with that of a self‐directed quit attempt.

Design and Setting. Data used were based primarily on results from a pharmacist‐directed smoking‐cessation program in a community pharmacy chain practice that achieved continuous abstinence for at least 1 year in 25% of patients. Baseline assumptions were formulated from a MEDLINE literature review and were varied in the sensitivity analysis. Overall costs were based on program costs and retail cost of the selected cessation method (cold turkey, nicotine patch, nicotine gum, or bupropion).

Patients. Forty‐eight patients, more than two thirds of whom were women, aged 21–70 years, who had tried at least once to quit smoking.

Measurements and Main Results. Incremental cost‐effectiveness was measured in terms of cost/successful quit attempt based on the payer's perspective. Cost/life‐year saved and cost/quality‐adjusted life‐year saved also were calculated for the societal perspective. Incremental cost for an additional patient to quit smoking using the pharmacist‐directed program alternatives versus a self‐directed quit attempt was $236 for the cold turkey method, $936 for nicotine patch, $1232 for nicotine gum, and $1150 for bupropion. Depending on the smoker's age at the time of cessation, the incremental discounted cost‐effectiveness was $720–1418/life‐year saved.

Conclusion. This analysis demonstrates that a pharmacist‐directed cessation program is a cost‐effective alternative to a self‐directed quit attempt with respect to payers and society. Additional analyses conducted in community pharmacy practice are necessary to corroborate our results.
Thrombotic Complications After Intravenous Immunoglobulin Therapy in Two Patients
Authors: Emerson Geoffrey G. , Herndon Christopher N. , Sreih Antoine G.
Published: June 2004

Although intravenous immunoglobulin (IVIg) generally is considered a safe treatment for various autoimmune and inflammatory disorders, rare cases of thrombosis may occur. We describe two patients who experienced thrombotic complications associated with IVIg therapy. A 54‐year‐old woman with idiopathic thrombocytopenia received IVIg 1 g/kg/day for 2 days. While receiving her infusion on day 2, she had an ischemic stroke with hemiparesis; 3 days later she developed deep vein thrombosis. A 33‐year‐old woman with Evans' syndrome received IVIg 400 mg/kg/day for 5 days and developed deep vein thrombosis 1 week after therapy was completed; she then received warfarin. Six months later, she received an additional course of IVIg for recurrent hemolytic anemia; 1 day later she died of pulmonary thromboembolism. We suggest that IVIg may promote thrombosis by increasing blood viscosity, activating platelets, or causing vasospasm and should be administered with caution.
Point‐of‐Care versus Laboratory Monitoring of Patients Receiving Different Anticoagulant Therapies
Authors: Reiss Robert A. , Haas Curtis E. , Griffis Deborah L. , Porter Bernadette , Tara Mary Ann
Published: June 2004

Study Objective. To compare point‐of‐care and standard hospital laboratory assays for monitoring patients receiving single or combination anticoagulant regimens.

Design. Prospective analysis.

Setting. Nursing units and clinics at a large, community hospital.

Patients. One hundred fifty patients receiving anticoagulants for cardiac, vascular, orthopedic, or cancer indications. Thirty patients were enrolled into each treatment group: warfarin, enoxaparin, heparin, warfarin plus enoxaparin, and warfarin plus heparin.

Intervention. Capillary and venous blood samples were collected once in each patient for simultaneous measurement of international normalized ratio (INR) and activated partial thromboplastin time (aPTT) by both assays.

Measurements and Main Results. Mean differences in paired INR and paired aPTT by point‐of‐care and standard assays were small, but 95% confidence intervals were wide. The INR differences were greater for the warfarin plus heparin group than for the warfarin group or warfarin plus enoxaparin group; clinical decision agreement was 47% for warfarin plus heparin, 73% for warfarin, and 93% for warfarin plus enoxaparin. The aPTT difference was greater for the warfarin plus heparin than for the heparin group; however, clinical decision agreement, 67% and 70%, respectively, was similar.

Conclusions. Point‐of‐care methods showed limited agreement with standard hospital laboratory assays of coagulation for all treatment groups. For INR values, significantly greater disagreement was noted between the assay methods for the warfarin plus heparin group compared with the warfarin group, but the agreement was similar for the warfarin and warfarin plus enoxaparin groups. Our data indicate that the point‐of‐care assays should not be considered interchangeable with standard laboratory assays.
Itraconazole and Fluconazole and Certain Rare, Serious Adverse Events
Authors: Bradbury Brian D. , Jick Susan S.
Published: June 2004

Study Objective. To determine rates of drug‐induced, rare, serious adverse events affecting the liver, kidneys, skin, or blood, occurring within 45 days of completing a prescription or refill for itraconazole or fluconazole.

Design. Population‐based follow‐up study.

Setting. United Kingdom‐based General Practice Research Database.

Patients. Total of 54,803 users of either fluconazole or itraconazole.

Main Results. Four patients were identified with illnesses for which a drug‐induced etiology could not be ruled out; one with an elevated liver function test while taking itraconazole, one with thrombocytopenia, one with neutropenia, and one with an abnormal liver function test just after receiving fluconazole. For itraconazole the rate was 3.2/100,000 prescriptions (95% confidence interval [CI] 0.6–17.9) for serious, adverse liver events; for fluconazole 2.8/100,000 prescriptions (95% CI 0.8–10.3) for serious, adverse blood events and 1.4/100,000 prescriptions (95% CI 0.25–8.2) for serious, adverse liver events.

Conclusion. Itraconazole and fluconazole do not commonly cause rare, serious adverse events affecting the liver, kidneys, skin, or blood.
Asthma Exacerbation After Administration of Nicotine Nasal Spray for Smoking Cessation
Authors: Roth Mary T. , Westman Eric C.
Published: June 2004

A 58‐year‐old man experienced an asthma exacerbation after administration of nicotine nasal spray for smoking cessation. His medical history was significant for asthma, chronic obstructive pulmonary disease, hypertension, and tobacco use when he was prescribed nicotine nasal spray for smoking cessation in an outpatient setting. Within the first 3 days of administering the spray, he developed wheezing, coughing, and significant shortness of breath, which required hospitalization. The patient was hospitalized for 48 hours and discharged with a diagnosis of asthma exacerbation probably related to administration of nicotine nasal spray. Prudent administration of nicotine nasal spray is recommended in patients with underlying respiratory disease. Patients should be counseled on the potential adverse effects of treatment and proper administration techniques in order to minimize these effects.
Levofloxacin‐Induced Toxic Epidermal Necrolysis in an Elderly Patient
Authors: Digwood‐Lettieri Shana , Reilly Kathleen J. , Haith Linwood R. , Patton Mary L. , Guilday Robert J. , Cawley Michael J. , Ackerman Bruce H.
Published: June 2004

Stevens‐Johnson syndrome and toxic epidermal necrolysis (TEN) are mild‐to‐life‐threatening adverse reactions that have been described after exposure to fluoroquinolones. No published reports, however, exist of exfoliative disease after treatment with levofloxacin. A 78‐year‐old woman with many medical problems, including chronic obstructive pulmonary disease, was treated with parenteral levofloxacin for community‐acquired pneumonia. She was discharged with oral levofloxacin to complete an additional 3 days of treatment as an outpatient. Two days after completing this regimen, the patient developed a rash with blistering. The rash progressed to TEN in 7 days, and she was transferred to a burn treatment center. She was treated with fluid resuscitation, wound dressing, and antibiotics. Her condition improved, and she was discharged after 22 days. To our knowledge, this case is the first published report of levofloxacin‐induced TEN.
Titelbild: Single DNA Rotaxanes of a Transmembrane Pore Protein (Angew. Chem. 23/2004)
Authors: Sánchez‐Quesada Jorge , Saghatelian Alan , Cheley Stephen , Bayley Hagan , Ghadiri M. Reza
Published: June 2004

Eine isolierte Rotaxanstruktur die durch Auffädeln und Arretieren eines DNA‐Poly(ethylenglycol)‐Stranges in einem α‐Hämolysin(α‐HL)‐Transmembranprotein entsteht, stellen M. R. Ghadiri et al. in ihrer Zuschrift auf S. 3125 ff. vor. Abhängig vom angelegten Potential, von der Orientierung, der Synthesemethode und der Stoppergruppe können die DNA‐α‐HL‐Rotaxane reversibel zwischen zwei Zuständen geschaltet werden. Aus der Studie lässt sich eine direkte Methode zum Abfangen von DNA‐Strängen definierter Länge und Sequenz ableiten.
Cover Picture: Single DNA Rotaxanes of a Transmembrane Pore Protein (Angew. Chem. Int. Ed. 23/2004)
Authors: Sánchez‐Quesada Jorge , Saghatelian Alan , Cheley Stephen , Bayley Hagan , Ghadiri M. Reza
Published: June 2004

A single rotaxane structure created by threading and capturing a DNA–poly(ethylene glycol) (DNA–PEG) strand inside an α‐hemolysin (α‐HL) transmembrane pore protein is described by M. R. Ghadiri and co‐workers on page 3063 ff. The DNA–α‐HL rotaxanes exhibit a reversible two‐state switching capacity that depends on the applied transmembrane potential, the orientation, and the method of threading and capture used. Functional rotaxanes might provide a means for critically assessing the feasibility of the pore‐mediated single‐molecule DNA sequencing hypothesis.
Defining the ecological values of rivers: the views of Australian river scientists and managers
Authors: Dunn Helen
Published: June 2004

The first step in making a case for river conservation is to define the particular values and attributes that describe conservation significance.

Australia's rivers vary widely in their characteristics and ecological communities. The conservation values of Australian rivers have not been well articulated.

A survey of Australian river scientists and managers was undertaken to identify the criteria and attributes of rivers of high ecological value. This was the first attempt to establish a baseline for defining natural conservation values for Australian rivers.

The final list comprised five broad criteria with a total of 47 attributes considered to be indicators of high ecological value. These included not only biotic values, but also values attributed to river hydrology, geomorphology, instream processes, and landscape functions.

The list of criteria and attributes provides a context from which specific values may be drawn to assess conservation values of rivers for particular purposes.

Copyright © 2004 John Wiley & Sons, Ltd.
Restoration of a small‐scale forest wetland in a Belgian nature reserve: a discussion of factors determining wetland vegetation establishment
Authors: Weyembergh Gisèle , Godefroid Sandrine , Koedam Nico
Published: June 2004

The main aim of this restoration attempt within a nature reserve was to recreate sustainable conditions for wetland species, particularly aquatic plants.

In the process of restoration, two phases of activity were distinguished: a pre‐restoration phase, during which information on land‐use history and past vegetation was collected and used to establish clear restoration goals; and a restoration phase for stimulating germination and establishment of target species originating from the soil seed bank and species pool.

Within the first year of the study, pond digging allowed the establishment of extremely rare native species that react positively to mudflat creation and standing water availability. The results of this experiment indicate that pond digging can be a very suitable technique for re‐establishing aquatic and wetland vegetation, providing that the site is well chosen.

An essential prerequisite for successful restoration is a study of the past vegetation of the target site and its surroundings. This work illustrates the importance of past vegetation in affecting current restoration success and provides an example of how restoration projects benefit from knowledge and understanding of both historical and present conditions.

Copyright © 2004 John Wiley & Sons, Ltd.
Assessing East African trade in seahorse species as a basis for conservation under international controls
Authors: McPherson Jana M. , Vincent Amanda C.J.
Published: June 2004

Seahorses (Hippocampus spp.), many of which are listed as Vulnerable or Endangered on the IUCN Red List, are traded worldwide as souvenirs, aquarium fish and, primarily, for use in traditional medicines. Given concern over the sustainability of this trade, the genus was added to Appendix II of the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) in May 2004.

This paper reports findings of the first ever survey of seahorse trade in Africa, conducted in Kenya and Tanzania in May and June 2000.

Seahorse trade in Kenya was found to be negligible, with approximately 10 live seahorses exported as aquarium fish annually. Until 1998, however, Kenya may have imported somewhere from 1 to 2.3 t of dried seahorses annually from Tanzania for re‐export to Asian medicine markets. Seahorse trade in Tanzania remained substantial, with at least 630–930 kg of dried seahorse exported directly to Asia each year.

Accounts of declines in seahorse availability and seahorse size, although few in number, could be early warning signs that wild populations are suffering, at least locally. Close monitoring of future developments in the trade will be essential to allow for timely conservation action as and when necessary, and would contribute to our understanding of the ecological and economical implications of small‐scale, non‐food fisheries.

Copyright © 2004 John Wiley & Sons, Ltd.
Construction of high‐density bacterial colony arrays and patterns by the ink‐jet method
Authors: Xu Tao , Petridou Sevastioni , Lee Eric H. , Roth Elizabeth A. , Vyavahare Narendra R. , Hickman James J. , Boland Thomas
Published: June 2004

We have developed a method for fabricating bacterial colony arrays and complex patterns using commercially available ink‐jet printers. Bacterial colony arrays with a density of 100 colonies/cm2 were obtained by directly ejecting Escherichia coli (E. coli) onto agar‐coated substrates at a rapid arraying speed of 880 spots per second. Adjusting the concentration of bacterial suspensions allowed single colonies of viable bacteria to be obtained. In addition, complex patterns of viable bacteria as well as bacteria density gradients were constructed using desktop printers controlled by a simple software program. © 2003 Wiley Periodicals, Inc.
Blocking caspase‐3 activity with a U6 SnRNA promoter‐driven ribozyme enhances survivability of CHO Cells Cultured in Low Serum Medium and Production of Interferon‐β
Authors: Lai Dazhi , Fu Ling , Weng Shaojie , Qi Lianquan , Yu Changming , Yu Ting , Wang Haitao , Chen Wei
Published: June 2004

Apoptosis responding to various insults in bioreactors was observed to reduce cell viability and prevent cells from growing to high density. Inhibition of apoptosis in different ways has proved to be effective in keeping cells viable in high density and result in higher recombinant protein production. In apoptosis, death signals activate a family of proteinases, namely caspases, in a cascade and ultimately activate the final effector proteinase, caspase‐3, which cleaves various substrates and drives the cells irreversibly to death. Caspase‐3 is the executioner of an apoptotic cell and thus plays a central role in apoptosis. Therefore inhibition of caspase‐3 may provide an effective way for apoptosis prevention. In this study, we designed a ribozyme targeted at the 451nt of hamster caspase‐3's open reading frame (ORF) and the ribozyme was proved to be effective in cleaving caspase‐3 mRNA in vitro. Then, the ribozyme was cloned into a vector under the control of U6 snRNA promoter, an RNA polymerase III promoter, for high rate of transcription in vivo. The vector was transfected into an interferon‐β producing recombinant CHO cell line, and some clones were screened out that exhibited low caspase‐3 production by Western blot analysis. One such clone was then further analyzed and it showed good anti‐apoptosis property with respect to cell viability, cell density, and interferon‐β production. © 2003 Wiley Periodicals, Inc.
Fluid mechanics of a spinner‐flask bioreactor
Authors: Sucosky Philippe , Osorio Diego F. , Brown Jason B. , Neitzel G. Paul
Published: June 2004

Spinner‐flask bioreactors have been used for the production of articular cartilage in vitro. The dynamic environment within bioreactors is known to significantly affect the growth and development of the tissue. The present research focuses on the experimental and numerical characterization of the flow field within a spinner flask operating under conditions used to produce cartilage. Laboratory experiments carried out in a scaled‐up model bioreactor employ particle‐image velocimetry (PIV) to determine velocity and shear‐rate fields in the vicinity of the construct closest to the stir bar, in addition to turbulence properties. Numerical computations calculated using FLUENT, a commercial software package, simulate the flow field in the same model bioreactor under similar operating conditions. In the computations, scaffolds were modeled as both solid and porous media with different permeabilities and flow rates through various faces of the construct nearest the stir bar were examined. © 2003 Wiley Periodicals, Inc.
Fundamental Escherichia coli biochemical pathways for biomass and energy production: Identification of reactions
Authors: Carlson Ross , Srienc Friedrich
Published: June 2004

Cells grow by oxidizing nutrients using a complex network of biochemical reactions. During this process new biological material is produced along with energy used for maintaining cellular organization. Because the metabolic network is highly branched, these tasks can be accomplished using a wide variety of unique reaction sequences. However, evolutionary pressures under carbon‐limited growth conditions likely select organisms that utilize highly efficient pathways. Using elementary‐mode analysis, we demonstrate that the metabolism of the bacterium Escherichia coli contains four unique pathways that most efficiently convert glucose and oxygen into new cells and maintenance energy under any level of oxygen limitation. Observed regulatory patterns and experimental findings suggest growing cells use these highly efficient pathways. It is predicted that five knockout mutations generate a strain that supports growth using only the most efficient reaction sequence. The analysis approach should be generally useful for predicting metabolic capabilities and efficient network designs based on only genomic information. © 2003 Wiley Periodicals, Inc.
Enhanced biological phosphorus removal in a sequencing batch reactor using propionate as the sole carbon source
Authors: Pijuan M. , Saunders A.M. , Guisasola A. , Baeza J.A. , Casas C. , Blackall L.L.
Published: June 2004

An enhanced biological phosphorus removal (EBPR) system was developed in a sequencing batch reactor (SBR) using propionate as the sole carbon source. The microbial community was followed using fluorescence in situ hybridization (FISH) techniques and Candidatus ‘Accumulibacter phosphatis’ were quantified from the start up of the reactor until steady state. A series of SBR cycle studies was performed when 55% of the SBR biomass was Accumulibacter, a confirmed polyphosphate accumulating organism (PAO) and when Candidatus ‘Competibacter phosphatis’, a confirmed glycogen‐accumulating organism (GAO), was essentially undetectable. These experiments evaluated two different carbon sources (propionate and acetate), and in every case, two different P‐release rates were detected. The highest rate took place while there was volatile fatty acid (VFA) in the mixed liquor, and after the VFA was depleted a second P‐release rate was observed. This second rate was very similar to the one detected in experiments performed without added VFA.

A kinetic and stoichiometric model developed as a modification of Activated Sludge Model 2 (ASM2) including glycogen economy, was fitted to the experimental profiles. The validation and calibration of this model was carried out with the cycle study experiments performed using both VFAs. The effect of pH from 6.5 to 8.0 on anaerobic P‐release and VFA‐uptake and aerobic P‐uptake was also studied using propionate. The optimal overall working pH was around 7.5. This is the first study of the microbial community involved in EBPR developed with propionate as a sole carbon source along with detailed process performance investigations of the propionate‐utilizing PAOs. © 2003 Wiley Periodicals, Inc.
Reconsidering the use of photosynthetic bacteria for removal of sulfide from wastewater
Authors: Hurse T.J. , Keller J.
Published: June 2004

The feasibility of using photosynthetic sulfide‐oxidizing bacteria to remove sulfide from wastewater in circumstances where axenic cultures are unrealistic has been completely reconsidered on the basis of known ecophysiological data, and the principles of photobioreactor and chemical reactor engineering. This has given rise to the development of two similar treatment concepts relying on biofilms dominated by green sulfur bacteria (GSB) that develop on the exterior of transparent surfaces suspended in the wastewater. The GSB are sustained and selected for by radiant energy in the band 720–780 nm, supplied from within the transparent surface. A model of one of these concepts was constructed and with it the reactor concept was proven. The dependence of sulfide‐removal rate on bulk sulfide concentration has been ascertained. The maximum net areal sulfide removal rate was 2.23 g m−2 day−1 at a bulk sulfide concentration of 16.5 mg L−1 and an incident irradiance of 1.51 W m−2. The system has a demonstrated capacity to mitigate surges in sulfide load, and appears to use much less radiant power than comparable systems. The efficacy with which this energy was used for sulfide removal was 1.47 g day−1 W−1. The biofilm was dominated by GSB, and evidence gathered indicated that other types of phototrophs were not present. © 2003 Wiley Periodicals, Inc.
Toluene removal from waste air using a flat composite membrane bioreactor
Authors: Jacobs Pieter , De Bo Inge , Demeestere Kristof , Verstraete Willy , Van Langenhove Herman
Published: June 2004

In this report, gaseous toluene biodegradation results in a flat composite membrane reactor inoculated with Pseudomonas putida TVA8 are presented. Preliminary abiotic experiments showed that transport of toluene through the membrane was linearly and negatively correlated with the gas residence time (τ). During a 339‐day biofiltration experiment, the influence of gas residence time (2–24 sec) and mass loading rate (Bv; 10–483 g m−3 h−1) on the toluene elimination capacity was investigated. A maximum elimination capacity (ECmax) of 397 g m−3 h−1 was achieved at τ = 24 sec and Bv = 473 g m−3 h−1. Expressed per unit membrane area, the ECm,max was 0.793 g m−2 h−1, which is five times higher than results obtained with other membrane bioreactor experiments in the same range of loading rates. At low gas residence times, reactor performance was limited by mass transfer. Toluene concentration profiles along the membrane were measured for several biotic and abiotic conditions. For inlet concentrations (Cin) up to 1 g m−3, more than 90% was eliminated at 15 cm from the reactor inlet. For Cin > 1.65 g m−3, longer membranes are necessary to obtain these high removal efficiencies. © 2003 Wiley Periodicals, Inc.
Overcoming shear stress of microalgae cultures in sparged photobioreactors
Authors: Barbosa Maria J. , Hadiyanto  , Wijffels René H.
Published: June 2004

In the present work we identified and quantified the effect of hydrodynamic stress on two different microalgae strains,Dunaliella tertiolectaandD. salina, cultivated in bench‐scale bubble columns. The cell death rate constant increased with increasing gas‐entrance velocity at the sparger.Dunaliella salinawas slightly more sensitive thanD. tertiolecta. The critical gas‐entrance velocities were ∼50 and 30 m s−1forD. tertiolectaandD. salina, respectively. The effects of gas‐flow rate, culture height, and nozzle diameter on the death rate constant were also studied. From these results it was concluded that bubble rising and bubble bursting are not responsible for cell death. Regarding nozzle diameter, small nozzles were more detrimental to cells. The bubble formation at the sparger was found to be the main event leading to cell death. © 2003 Wiley Periodicals, Inc.
Analysis of size distribution and areal cell density of ammonia‐oxidizing bacterial microcolonies in relation to substrate microprofiles in biofilms
Authors: Okabe Satoshi , Kindaichi Tomonori , Ito Tsukasa , Satoh Hisashi
Published: June 2004

A fine‐scale in situ spatial organization of ammonia‐oxidizing bacteria (AOB) in biofilms was investigated by combining molecular techniques (i.e., fluorescence in situ hybridization (FISH) and 16S rDNA‐cloning analysis) and microelectrode measurements. Important parameters of AOB microcolonies such as size distribution and areal cell density of the microcolonies were determined and correlated with substrate microprofiles in the biofilms. In situ hybridization with a nested 16S rRNA‐targeted oligonucleotide probe set revealed two different populations of AOB, Nitrosomonas europaea‐lineage and Nitrosospira multiformis‐lineage, coexisting in an autotrophic nitrifying biofilm. Nitrosospira formed looser microcolonies, with an areal cell density of 0.51 cells μm−2, which was half of the cell density of Nitrosomonas (1.12 cells μm−2). It is speculated that the formation of looser microcolonies facilitates substrate diffusion into the microcolonies, which might be a survival strategy to low O2 and NH conditions in the biofilm. A long‐term experiment (4‐week cultivation at different substrate C/N ratios) revealed that the size distribution of AOB microcolonies was strongly affected by better substrate supply due to shorter distance from the surface and the presence of organic carbon. The microcolony size was relatively constant throughout the autotrophic nitrifying biofilm, while the size increased by ∼80% toward the depth of the biofilm cultured at the substrate C/N = 1. A short‐term (∼3 h) organic carbon addition experiment showed that the addition of organic carbon created interspecies competition for O2 between AOB and heterotrophic bacteria, which dramatically decreased the in situ NH‐uptake activity of AOB in the surface of the biofilms. This result might explain the spatial distribution of AOB microcolony size in the biofilms cultured at the substrate C/N = 1. These experimental results suggest O2 and organic carbon were the main factors controlling the spatial organization and activity of AOB in biofilms. These findings are significantly important to further improve mathematical models used to describe how the slow‐growing AOB develop their niches in biofilms and how that configuration affects nitrification performance in the biofilm. © 2003 Wiley Periodicals, Inc.
Cephalosporin C production by immobilized Cephalosporium acremonium cells in a repeated batch tower bioreactor
Authors: Cruz Antonio J. G. , Pan Tai , Giordano Roberto C. , Araujo Maria Lucia G. C. , Hokka Carlos O.
Published: June 2004

The industrial production of antibiotics with filamentous fungi is usually carried out in conventional aerated and agitated tank fermentors. Highly viscous non‐Newtonian broths are produced and a compromise must be found between convenient shear stress and adequate oxygen transfer. In this work, cephalosporin C production by bioparticles of immobilized cells of Cephalosporium acremonium ATCC 48272 was studied in a repeated batch tower bioreactor as an alternative to the conventional process. Also, gas‐liquid oxygen transfer volumetric coefficients, kLa, were determined at various air flow‐rates and alumina contents in the bioparticle. The bioparticles were composed of calcium alginate (2.0% w/w), alumina ( < 44 micra), cells, and water. A model describing the cell growth, cephalosporin C production, oxygen, glucose, and sucrose consumption was proposed. To describe the radial variation of oxygen concentration within the pellet, the reaction‐diffusion model forecasting a dead core bioparticle was adopted. The kLa measurements with gel beads prepared with 0.0, 1.0, 1.5, and 2.0% alumina showed that a higher kLa value is attained with 1.5 and 2.0%. An expression relating this coefficient to particle density, liquid density, and air velocity was obtained and further utilized in the simulation of the proposed model. Batch, followed by repeated batch experiments, were accomplished by draining the spent medium, washing with saline solution, and pouring fresh medium into the bioreactor. Results showed that glucose is consumed very quickly, within 24 h, followed by sucrose consumption and cephalosporin C production. Higher productivities were attained during the second batch, as cell concentration was already high, resulting in rapid glucose consumption and an early derepression of cephalosporin C synthesizing enzymes. The model incorporated this improvement predicting higher cephalosporin C productivity. © 2003 Wiley Periodicals, Inc.
Combined in‐fermenter extraction and cross‐flow microfiltration for improved inclusion body processing
Authors: Tin Lee Chew , Morreale Giacomo , Middelberg Anton P. J.
Published: June 2004

In this study we demonstrate a new in‐fermenter chemical extraction procedure that degrades the cell wall of Escherichia coli and releases inclusion bodies (IBs) into the fermentation medium. We then prove that cross‐flow microfiltration can be used to remove 91% of soluble contaminants from the released IBs. The extraction protocol, based on a combination of Triton X‐100, EDTA, and intracellular T7 lysozyme, effectively released most of the intracellular soluble content without solubilising the IBs. Cross‐flow microfiltration using a 0.2 μm ceramic membrane successfully recovered the granulocyte macrophage‐colony stimulating factor (GM‐CSF) IBs with removal of 91% of the soluble contaminants and virtually no loss of IBs to the permeate. The filtration efficiency, in terms of both flux and transmission, was significantly enhanced by in‐fermenter Benzonase® digestion of nucleic acids following chemical extraction. Both the extraction and filtration methods exerted their efficacy directly on a crude fermentation broth, eliminating the need for cell recovery and resuspension in buffer. The processes demonstrated here can all be performed using just a fermenter and a single cross‐flow filtration unit, demonstrating a high level of process intensification. Furthermore, there is considerable scope to also use the microfiltration system to subsequently solubilise the IBs, to separate the denatured protein from cell debris, and to refold the protein using diafiltration. In this way refolded protein can potentially be obtained, in a relatively pure state, using only two unit operations. © 2003 Wiley Periodicals, Inc.
Total Oxidation of Methane and Chlorinated Hydrocarbons on Zirconia Supported A1–xSrxMnO3 Catalysts
Authors: Stephan K. , Hackenberger M. , Kießling D. , Wendt G.
Published: June 2004

The catalytic behavior of ZrO2 and ZrO2 containing 8 mol‐% Y2O3 supported A1–xSrxMnO3 (A = La, didymium) perovskites was studied in the total oxidation of methane, chloromethane and dichloromethane considering catalyst deactivation and byproduct formation. The perovskites are dispersed on the support surface; clusters with a perovskite‐like structure were formed. The supported catalysts are characterized by higher specific surface areas compared with the unsupported ones. Partial substitution of A‐site cations by Sr leads to an enhancement of the catalytic activity in the total oxidation of methane, but not in the total oxidation of chlorinated hydrocarbons (CHC). The catalytic activity of supported and unsupported catalysts is comparable in the total oxidation of methane in spite of the significantly lower perovskite content of the supported catalysts. In the CHC conversion the catalytic activity of the supported catalysts is higher than that of the unsupported ones.
Optimal Production Planning for Chemical Processes under Uncertain Market Conditions
Authors: Li P. , Wendt M. , Wozny G.
Published: June 2004

Due to lack of a systematic reliability analysis, intuitive decisions can often be made in production planning under uncertainty. These decisions will lead to either conservative or aggressive production. In this work, we propose a novel analysis and optimization framework to address this problem, with which the relationship between the profitability and reliability of a planned operation can be quantified. By using probabilistic programming, the solution of the problem provides comprehensive information on the economical achievement as a function of the desired confidence level of satisfying process constraints. The feasible region will shrink and the profit will decrease when increasing the confidence level. For complex plant operations under multiple uncertainties, the sources of risk that have the most significant impacts on the profitability can be identified. Through this approach, an optimal as well as reliable decision for operations can be made, from which a suitable compensation between the profit and the probability of constraints violation can be received. The approach is applied to three problems of production planning under uncertainty and various issues in planning these operations are discussed.
Mass Transfer Modeling of SO2 into Large Water Drops
Authors: Alexandrova S. , Marion M. , Lepinasse E. , Saboni A.
Published: June 2004

This article concerns the modeling of the SO2 absorption and desorption by falling drops through air with low to high concentration of sulfur dioxide. In the liquid phase, a model based on local scales, interfacial liquid friction velocity and drop size diameter is used. In the continuous gas phase a more classical model is applied. Data obtained by the modeling of the SO2 absorption and desorption by a single water drop are compared to published experimental results and a fairly good correspondence was found. On the other hand, the model shows that at high gas concentration (> 1 %) the internal resistance to diffusion dominates, while at low gas concentration (< 1000 ppb) the external resistance to diffusion dominates.
Video Microscopy for Fast Screening of Polymerization Catalysts
Authors: Abboud M. , Kallio K. , Reichert K.‐H.
Published: June 2004

Video microscopy has been used as an effective tool for fast screening of six different metallocene/MAO supported catalyst samples. The different techniques employed for supporting the metallocene on silica gels can have an influence on the overall catalyst activity and on the activity of single catalyst particles. The kinetics of gas‐phase polymerization of ethylene with supported metallocene/MAO catalysts can be modeled by using a simple reaction scheme and neglecting mass and heat transport effects.
Examination of External Mass Transport in a Microchannel Reactor by Pressure Variation
Authors: Kölbl A. , Pfeifer P. , Fichtner M. , Kraut M. , Schubert K. , Liauw M.A. , Emig G.
Published: June 2004

A variation of total pressure may be used to check for external mass transfer limitation in heterogeneous catalytic experiments. This is particularly interesting for microchannel reactor studies where a variation of flow rate is not suitable. The pressure variation approach is demonstrated for the steam reforming of methanol in a microstructured reactor. The result is verified by another method, viz. the variation of the carrier gas. The two methods are in good agreement. Other implications of a pressure variation in microchannels are discussed.