bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Safety of Filgrastim versus Sargramostim in Patients Receiving Myelosuppressive Chemotherapy
Authors: Milkovich Gary , Moleski Ronald J. , Reitan John F. , Dunning David M. , Gibson Gene A. , Paivanas Thomas A. , Wyant Susan , Jacobs R. Jake
Published: June 2004

Study Objective. To compare rates of adverse events with filgrastim versus sargramostim when given prophylactically to patients receiving myelosuppressive chemotherapy.

Design. Retrospective review with center crossover.

Setting. Ten United States outpatient chemotherapy centers.

Patients. Four hundred ninety patients treated for lung, breast, lymphatic system, or ovarian tumors.

Intervention. Prophylactic use of filgrastim or sargramostim, with dosages at investigator discretion.

Measurements and Main Results. The frequency and severity of adverse events and the frequency of switching to the alternative CSF were assessed. There was no difference in infectious fever. Fever unexplained by infection was more common with sargramostim (7% vs 1%, p<0.001), as were fatigue, diarrhea, injection site reactions, other dermatologic disorders, and edema (all p<0.05). Skeletal pain was more frequent with filgrastim (p=0.06). Patients treated with sargramostim switched to the alternative agent more often (p<0.001).

Conclusion. Adverse events were less frequent with filgrastim than with sargramostim, suggesting that quality of life and treatment costs also may differ.
The Low‐Density Lipoprotein Cholesterol‐Lowering Effect of Pravastatin and Factors Associated with Achieving Targeted Low‐Density Lipoprotein Levels in an African‐American Population
Authors: Chong Pang H. , Tzallas‐Pontikes Pamala J. , Seeger John D. , Stamos Thomas D.
Published: June 2004

Study Objectives. To describe the low‐density lipoprotein cholesterol (LDL)‐lowering effect of pravastatin in African‐American patients and to identify factors associated with achieving National Cholesterol Education Program (NCEP)‐defined target levels.

Design. Retrospectively defined cohort study.

Setting. Large, government‐owned, teaching hospital.

Patients. Eighty‐four African‐American patients starting therapy with pravastatin in October‐November 1997.

Measurements and Main Results. Whether or not target LDL concentrations were achieved was used to measure efficacy. Stepwise logistic regression identified the target LDL, baseline LDL, and baseline high‐density lipoprotein cholesterol (HDL) as significant predictors of achieving the target. The proportion of patients achieving their target LDL when that target was below 160, below 130, and 100 mg/dl or below was 64%, 32%, and 13% (p=0.004), respectively. Medical record review identified the reasons for not achieving target as incorrect drug regimen, inadequate lipid monitoring, and noncompliance.

Conclusion. These results indicate that substantial numbers of patients receiving lipid‐lowering therapy are not meeting NCEP‐defined targets and that with increased drug monitoring and compliance, improvements in achieving NCEP target LDL levels could be realized.
Enzymatic Shunting: Resolving the Acetaminophen‐Warfarin Controversy
Authors: Lehmann David F.
Published: June 2004

Observational studies in patients have shown a dose‐dependent enhancement of the anticoagulant effect of warfarin by acetaminophen whereas pharmacodynamic studies in healthy human volunteers have shown no such effect. This controversy is further intensified because any interaction between acetaminophen and racemic warfarin can involve only the weaker R‐warfarin enantiomer. Certain drugs exclusively competing for the metabolism of R‐warfarin enhance the anticoagulant effect of racemic warfarin and others do not. Because R‐warfarin is a weak inhibitor of vitamin K epoxide reductase and is metabolized by cytochrome P450 (CYP) 1A2 and 3A4, it is hypothesized that simultaneous competition with R‐warfarin for CYP1A2 and 3A4 is required for drug interactions to be clinically significant with compounds exclusively affecting the R enantiomer, such as acetaminophen. The discrepant observations in the literature regarding the clinical significance of the acetaminophen‐warfarin interaction may be resolved if the hepatic enzyme activity of CYP1A2 and 3A4 is enhanced relative to CYP2E1 and the nonoxidative pathways of glucuronidation and sulfation responsible for acetaminophen metabolism. Conditions such as aging and tissue hypoxia alter the relative activity of these enzymatic pathways in vitro and in small human studies. These phenomena may be manifested clinically when acetaminophen is administered to older anticoagulated patients and those with conditions that affect cardiac output such as atrial fibrillation and congestive heart failure. Verifying this hypothesis may provide insight into the clinically relevant interplay between common conditions as they affect oxidative and nonoxidative pathways of drug metabolism.
Quinupristin‐Dalfopristin: An Overview
Authors: Delgado George , Neuhauser Melinda M. , Bearden David T. , Danziger Larry H.
Published: June 2004

Synercid (RP 59500), the first injectable streptogramin antibiotic, is composed of two semisynthetic pristinamycin derivatives, quinupristin and dalfopristin. Individually, each component has bacteriostatic activity against staphylococci and streptococci, but together, the agents exhibit synergy, leading to bactericidal activity. The combination drug, however, is bacteriostatic against Enterococcus faecium and has poor activity against Enterococcus faecalis. Despite a short half‐life, an extended postantibiotic effect allows the agent to be dosed every 8–12 hours. Both drugs are largely hepatically metabolized and excreted in bile. Although not metabolized by cytochrome P450 3A4, quinupristin‐dalfopristin can inhibit agents that are metabolized through this pathway. Dosage adjustments may be necessary in patients with hepatic dysfunction. Alterations in renal function have minimal effects on the agent's pharmacokinetics. Adverse events include arthralgia, myalgias, and infusion‐related pain. Based on available data, quinupristin‐dalfopristin appears to have a role in treating severely ill patients with infections due to multiresistant gram‐positive pathogens.
Intolerance to Intragastric Enteral Nutrition in Critically Ill Patients: Complications and Management
Authors: MacLaren Robert
Published: June 2004

Compared with parenteral nutrition, early administration of enteral nutrition (EN) to critically ill patients improves clinical outcomes and reduces infection rates. Intragastric EN often is complicated by intolerance, as indicated by elevated volumes of aspirated gastric residuals. Conflicting data are available for the volume of residual that represents intolerance, but most clinicians use 150–200 ml to signify gastrointestinal motility dysfunction. Intolerance is associated with mortality. Data support an association between intragastric EN and aspiration pneumonia, but little information is available regarding the contributory effect of intolerance. Transpyloric migration of the feeding tube may facilitate tolerance but does not reduce the likelihood of aspiration pneumonia. Prokinetic agents (cisapride, erythromycin, metoclopramide) promote gastric emptying. Results of most studies are limited because patients did not receive or tolerated intragastric EN. Metoclopramide is the agent of choice for treating intolerance. Further studies are necessary before prokinetic drugs can be recommended for preventing intragastric EN‐associated aspiration pneumonia.
Coinfection with HIV and HCV: More Questions than Answers?
Authors: Waldrep Travis W. , Summers Kimberly K. , Chiliade Philippe A.
Published: June 2004

Chronic infection with the hepatitis C virus (HCV) is a major public health threat in the United States and worldwide. By sharing some routes of transmission, persons infected with the human immunodeficiency virus (HIV) are at risk for coinfection with HCV. As a result, hepatic cirrhosis, end‐stage liver disease, and hepatocellular carcinoma due to chronic infection with HCV are important causes of both morbidity and mortality in coinfected patients. The advent of highly active antiretroviral therapy improved the management of patients with HIV, leading to decreased morbidity and better survival. As patients infected with HIV live longer, their risk of long‐term sequelae from chronic HCV increases. Coinfection with HIV may be associated with rapid progression of chronic HCV. In contrast, the effect of HCV on the natural history of HIV is less clear. Data regarding treatment of HCV in HIV‐coinfected patients are limited.
Mefloquine‐Induced Acute Hepatitis
Authors: Gotsman Israel , Azaz‐Livshits Tanya , Fridlender Zvi , Muszkat Mordechai , Ben‐Chetrit Eldad
Published: June 2004

Mefloquine is an effective drug for prophylaxis and treatment of malaria caused by Plasmodium falciparum. It is generally well tolerated with few side effects. Minimal elevation of liver function tests has been reported after exposure to mefloquine, especially in susceptible individuals with prior abnormal liver function tests. Our patient, who had had elevated liver function tests attributed to heart failure, experienced an acute elevation of liver transaminases 6 weeks after exposure to mefloquine 250 mg/week. Cessation of the drug caused test results to return to normal. Mefloquine should be prescribed cautiously in patients with liver disease.
Anaphylactoid Reaction to Levofloxacin
Authors: Smythe Maureen A. , Cappelletty Diane M.
Published: June 2004

Anaphylactoid and/or anaphylactic reactions to fluoroquinolones are estimated to occur in 0.46–1.2/100,000 patients. A 49‐year‐old woman with a history of asthma was admitted for a presumed asthma exacerbation related to an infectious process. She was given levofloxacin and standard management for an acute exacerbation. On two occasions the patient's respiratory distress worsened, requiring intubation. The second reaction occurred immediately after levofloxacin administration and was accompanied by a marked cutaneous reaction. Levofloxacin was discontinued, and supportive care was provided. No further symptoms occurred. The patient later was found to have been started on levofloxacin before admission for a suspected upper respiratory infection.
Moxifloxacin, a New Antibiotic Designed to Treat Community‐Acquired Respiratory Tract Infections: A Review of Microbiologic and Pharmacokinetic‐Pharmacodynamic Characteristics
Authors: Nightingale Charles H.
Published: June 2004

Moxifloxacin (BAY 12–8039) is a new 8‐methoxy‐fluoroquinolone antibacterial agent. The minimum inhibitory concentration for 90% of organisms (MIC90) is less than 0.25 mg/L for commonly isolated community‐acquired respiratory tract pathogens including penicillin‐susceptible and ‐resistant Streptococcus pneumoniae, Haemophilus sp, and Moraxella catarrhalis, and less than 1.0 mg/L for atypical pathogens such as Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila. To date, emergence of resistance to moxifloxacin has been uncommon, including selection of resistance under experimental conditions (methicillin‐sensitive Staphylococcus aureus, S. pneumoniae). A postantibiotic effect is observed for both gram‐positive and gram‐negative bacteria. Human pharmacokinetics in healthy volunteers after a single 400‐mg oral dose were mean maximum concentration (Cmax) 3.2 mg/L, area under the curve (AUC) 37 mg•hour/L, and terminal elimination half‐life 12.0 hours. At steady‐state, Cmax and AUC were approximately 4.5 mg/L and 48 mg•hour/L, respectively. Because of a balanced system of excretion, no dosage adjustments are required in patients with renal or hepatic impairment. Moxifloxacin also has excellent penetration into upper and lower respiratory tissues. Laboratory pharmacodynamic models suggest that MIC and AUC values predict therapeutic response. Notably, the drug can be administered once/day and is not associated with drug interactions secondary to altered hepatic metabolism. In addition, since its metabolism does not involve the cytochrome P450 system, many common drug interactions are absent. The agent is being investigated in clinical trials and shows promise as a safe and effective once‐daily treatment of respiratory infections. In addition, its chemical structure and pharmacokinetic and pharmacodynamic properties indicate that it has enhanced potential to minimize emergence of bacterial resistance, which should make it an excellent choice for treating respiratory tract infections now and in the future.
Safety Issues with Herbal Medicine
Authors: Boullata Joseph I. , Nace Angela M.
Published: June 2004

As herbal medicines are used by increasing numbers of people, pharmacists must be knowledgeable about their safety. This requires appreciation of the magnitude of use, as well as regulations under which the products are marketed that may affect their safety. Unexpected effects of many popular herbal products are described in the literature. Thus the pharmacist's role in ensuring protection of the consumer continues to grow.
Altering the Estrogenic Milieu of Breast Cancer with a Focus on the New Aromatase Inhibitors
Authors: Higa Gerald M.
Published: June 2004

Aromatase is a dual‐enzyme complex that catalyzes the synthesis of estrogen from androgenic precursors. Although evidence implicates estrogens in the pathogenesis of breast cancer, recent findings suggest that deregulation of aromatase may be a crucial link between these hormones and this neoplasm. Whereas tamoxifen is the endocrine therapy of choice, selective inhibition of aromatase may be equally effective, and possibly less toxic, in the management of patients with hormone‐responsive breast tumors.
Evaluation and Management of Drug‐Induced Thrombocytopenia in the Acutely Ill Patient
Authors: Wazny Lori D. , Ariano Robert E.
Published: June 2004

The numerous drugs to which the acutely ill are exposed place these patients at a significant risk of developing drug‐induced thrombocytopenia. Such patients tend to have preexisting hemostatic defects that place them at additional risk of complications as a result of the drug‐induced thrombocytopenia. The clinical challenge is to provide rapid identification and removal of the offending agent before clinically significant bleeding or, in the case of heparin, thrombosis results. Drug‐induced thrombocytopenic disorders can be classified into three mechanisms: bone marrow suppression, immune‐mediated destruction, and platelet aggregation. Clinical characteristics, preliminary laboratory findings, and drug history specific to the mechanisms can assist clinicians in rapidly isolating the causative drug.
Psychotropic Drugs and Falls: New Evidence Pertaining to Serotonin Reuptake Inhibitors
Authors: Sleeper Rebecca , Bond C. A. , Rojas‐Fernandez Carlos
Published: June 2004

Falls are a significant cause of fatal and nonfatal injuries in older persons. Risk factors include previous falls, several disease states, and certain drugs such as tricyclic antidepressants and antihypertensives. We conducted a MEDLINE search from January 1966–March 1999 to identify studies and review articles on the association of neuroleptics, benzodiazepines, and antidepressants with fall risk in older people. The focus was on the risk associated with serotonin reuptake inhibitors, biologic plausibility, and limitations of these studies. It was thought that the agents did not increase the risk of falls, although recent evidence suggests that this is not the case.
Open‐Label, Nonrandomized Study of the Effects of Gatifloxacin on the Pharmacokinetics of Midazolam in Healthy Male Volunteers
Authors: Grasela Dennis M. , LaCreta Frank P. , Kollia Georgia D. , Randall Diane M. , Uderman Howard D.
Published: June 2004

Study Objective. To confirm findings from an in vitro study that showed gatifloxacin did not substantially inhibit cytochrome P450 (CYP) 3A4 model substrate metabolism.

Design. Open‐label, nonrandomized trial.

Setting. Clinical pharmacology unit.

Subjects. Fourteen healthy adult men.

Intervention. Using midazolam probe methodology, the clearance of midazolam in the presence of multiple‐dose gatifloxacin was evaluated.

Measurements and Main Results. Typical steady‐state concentrations of gatifloxacin 400 mg once/day had no effect on midazolam clearance, and gatifloxacin pharmacokinetics were unaffected by midazolam. All doses of both agents were well tolerated.

Conclusion. Data from this in vivo trial support in vitro experience with gatifloxacin and suggest that interactions are unlikely between gatifloxacin and drugs that are metabolized by CYP3A.
Absorption of Phenytoin from Rectal Suppositories Formulated with a Polyethylene Glycol Base
Authors: Burstein Aaron H. , Fisher Karen M. , McPherson M. Lynn , Roby Carol A.
Published: June 2004

Study Objective. To compare phenytoin pharmacokinetics following administration of an oral suspension and a rectal suppository formulated with a polyethylene glycol base.

Design. Unblinded, single‐dose, randomized, crossover trial.

Setting. University‐affiliated pharmacokinetics and biopharmaceutics laboratory.

Subjects. Six healthy subjects.

Intervention. Subjects were given a single 200‐mg dose of phenytoin as an oral suspension and a rectal suppository separated by a 1‐week washout.

Measurements and Main Results. Blood for plasma phenytoin concentrations was obtained at baseline and 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours after administration. Plasma was analyzed by high‐performance liquid chromatography (coefficient of variation < 6%) for total phenytoin concentration. Phenytoin maximum concentration (Cmax), time to Cmax (Tmax), time to first measurable concentration (Tlag), and area under the curve from time zero to time of last measurable concentration (AUClast) were estimated for oral and rectal administration by WinNonlin (v 1.1) and compared using Wilcoxons signed rank test (p<0.05 for statistical significance). Two subjects did not have detectable plasma phenytoin concentrations after rectal administration. For the other four subjects, median rectal Cmax was significantly lower than oral Cmax (0.4 vs 1.9 μg/ml, p=0.028), median rectal Tmax did not differ from oral Tmax (11.9 vs 8.0 hrs, p=0.465), and median rectal AUClast, although highly variable, was significantly lower than oral AUClast (5.4 vs 36.2 μg•hr/ml, p=0.046). No Tlag was seen after oral administration, but with rectal administration the median Tlag was 2 hours. The estimated relative bioavailability of rectal phenytoin suppositories based on AUC0–24 was 4.7%, with individual values ranging from 0–58.3%.

Conclusion. It appears that absorption of phenytoin from polyethylene glycol rectal suppositories in healthy subjects is highly variable and unpredictable. Thus this formulation is not recommended.
Brillouin–Wigner Expansions for Molecular Electronic Structure
Authors: Hubač Ivan , Wilson Stephen
Published: June 2004

The use of Brillouin–Wigner expansions in describing electron correlation effects in systems requiring the use of a multireference formalism is described. Brillouin–Wigner‐based methods avoid the intruder state problem which plagues Rayleigh–Schrödinger‐based methods. Such methods can be applied to many‐body systems either(i)by applying the Brillouin–Wigner expansion to solve the equations of an explicitly many‐body method; or(ii)by developinga posterioricorrections. The Brillouin–Wigner coupled cluster theory is presented in both its single reference and multireference forms. Single and multireference configuration interaction expansions are described together with the accompanyinga posterioricorrection procedures.
Molecular Complexes: Perturbations of Vibrational Spectra
Authors: Ford Thomas A.
Published: June 2004

The structures, interaction energies, and vibrational spectra of a series of molecular complexes containing boron trifluoride as the electron acceptor and a variety of oxygen, nitrogen, sulfur, and halogen bases as the electron donors have been computed. The effects of the molecular interactions on the vibrational properties of the boron trifluoride species have been studied, and the degree of perturbation has been correlated with some of the properties of the bases.
Retrospective reports of organizational commitment after Russian military downsizing
Authors: Kwong Jessica Y. Y. , Hamilton V. Lee
Published: June 2004

This paper assesses the accuracy of people's memories of attitudes and explores sources of errors in the recollection. We did a secondary analysis on a panel survey of the Russian Army's officer corps, conducted before and after its downsizing. The dependent measure was the discrepancy between Army officers' prospective and retrospective organizational commitment ratings made 18 months apart. We linked this discrepancy to the officers' sense of mastery and evaluations of job prospects across the two waves. In general, officers tended to overestimate their prior commitment to the Army. The amount of overestimation was positively related to both officers' initial level and the subsequent increase in mastery, but was negatively related to their perceived immediate job prospects. Possible mechanisms for the distortion and conceptual implications are discussed. Copyright © 2004 John Wiley & Sons, Ltd.
Going shopping and identifying landmarks: does collaboration improve older people's memory?
Authors: Ross Michael , Spencer Steven J. , Linardatos Lisa , Lam Kent C. H. , Perunovic Mihailo
Published: June 2004

Older participants (mean age = 72.82 years) attempted to recall items from shopping lists while shopping in a supermarket and subsequently in their homes on recognition tests. They also attempted to identify local landmarks on a map. The recall occurred either together with their spouses or independently. Collaborative recall was compared to the pooled, nonredundant recall of spouses who completed the memory tasks alone (nominal groups). Nominal groups produced more hits on most measures and never fewer hits than did collaborative groups. However, collaborative groups consistently generated fewer memory errors than did nominal groups. In many everyday contexts, a tendency for collaboration to reduce false recall could be advantageous to older people. Signal detection analyses revealed that collaboration leads couples to require a higher level of certainty before they are willing to claim that they recognize an item. Finally, we examined the relation between expertise and recall in the shopping and landmark tasks. Copyright © 2004 John Wiley & Sons, Ltd.
How knowing and doing inform an autobiography: relations among preschoolers' theory of mind, narrative, and event memory skills
Authors: Kleinknecht Erica , Beike Denise R.
Published: June 2004

Research on the development of autobiographical memory in children has revealed the importance of two seemingly separate but related factors: Theory of mind, or the ability to know what another can and cannot know, and narrative skill, or the ability to tell a coherently structured story. The present research study with 22 preschoolers examined the extent to which each factor predicts two separate components of autobiographical memory ability: (1) the content of memory and (2) the structure of the memory narrative. As hypothesized, we found that theory of mind skills predicted the ‘how’ or structure of the children's fictional story narratives, whereas narrative skills predicted the ‘how much’ or content of the children's memory. Implications for the development of autobiographical memory are discussed. Copyright © 2004 John Wiley & Sons, Ltd.
Post‐identification feedback, confidence and recollections of witnessing conditions in child witnesses
Authors: Hafstad Gertrud Sofie , Memon Amina , Logie Robert
Published: June 2004

Eyewitness confidence and detailed memory reports are often considered reliable indicators of the credibility of the eyewitness testimony. This study investigated how feedback concerning the accuracy of a lineup identification influences witnesses' confidence in the accuracy of their identification decision and their judgements concerning the witnessing experience. Fifty‐seven children (11–12 years) and 55 adults (17–39 years) viewed a video of a robbery and attempted to identify the culprit from a photo lineup. The culprit was not present. Participants received confirming feedback, disconfirming feedback, or no feedback on the accuracy of their identification. The confidence judgements and recollections of witnessing conditions of both children and adults were influenced by confirming and in some instances, disconfirming feedback. These findings imply that confidence and memory reports are easily distorted by non‐specific feedback and investigators should be sensitive to this particularly when dealing with vulnerable witnesses such as children. Copyright © 2004 John Wiley & Sons, Ltd.
Facets of personality and the phenomenology of autobiographical memory
Authors: Rubin David C. , Siegler Ilene C.
Published: June 2004

The relationship between individual differences in autobiographical memory and personality was examined by having 118 undergraduates complete the NEO Personality Inventory after rating 15 word‐cued autobiographical memories on 20 scales. The Openness to Feelings facet (O3) correlated with measures of belief in the accuracy of memories, recollection, sensory imagery and emotion. Four other facets had correlations with belief (A3—Altruism, E1—Warmth, E4—Activity, E6—Positive Emotions). These facets also deal with emotional components of personality. In multiple regressions, measures of belief and measures of recollection were predicted by different variables, and for measures of belief, the O3 facet increased the variance accounted for beyond that of just the cognitive variables. Our results are consistent with and extend studies of the effects of depression and emotional suppression on autobiographical memory. Copyright © 2004 John Wiley & Sons, Ltd.
Risk and the recognition of driving situations
Authors: Chapman Peter , Groeger John A.
Published: June 2004

This paper reports a series of experiments that explore the relationship between subjective risk when viewing driving situations and subsequent recognition memory for such films. In the first experiment no simple relationship was found between risk and recognition performance. Instead the experience of subjective risk was associated with good recognition of generally dangerous situations but poor recognition of generally safe ones. The remaining experiments replicated this result and explored possible reasons for it. An account of the results in terms of schema theory was tested and rejected. The effect is instead interpreted in terms of the types of information that are present and attended to in different kinds of dangerous situation. Overall recognition memory for films of driving situations was surprisingly poor, but the pattern of results was consistent with drivers showing good memory for central details from dangerous situations. Copyright © 2004 John Wiley & Sons, Ltd.
Measuring velocity distributions of viscous fluids using positron emission particle tracking (PEPT)
Authors: Bakalis S. , Fryer P. J. , Parker D. J.
Published: June 2004

Positron emission particle tracking (PEPT) can be used to trace the path of a radioactive particle within opaque fluids in pilot‐scale equipment; the method can track particles through several centimeters of metal. PEPT has been successfully used to follow isokinetic tracers in viscous fluids and thus to measure velocity distributions under both isothermal and nonisothermal conditions in pipe flow. The accuracy of the method decreased as the measured velocities increased; the faster the particle traveled, the less accurate its detection. For velocities of up to 0.5 m/s the accuracy of the method was acceptable. Agreement between experimentally measured and theoretical velocity distributions was very good, for a range of fluids and process conditions. As tracer particles are used, there were problems ensuring that all parts of the measurement volume were sampled. This is possible to overcome to an extent by adjusting particle size; 600‐μm tracers did not pass within 1 mm from the tube wall, whereas 240‐μm particles passed much closer to the boundaries of the flow. © 2004 American Institute of Chemical Engineers AIChE J, 50: 1606–1613, 2004
Two novel mutations of PTEN gene in Japanese patients with Cowden syndrome
Authors: Sawada Takeshi , Okada Toshihide , Miwa Kazuhiro , Satoh Hiro , Asano Akimichi , Mabuchi Hiroshi
Published: June 2004

Cowden syndrome (CS), also known as multiple hamartoma syndrome, is an autosomal dominant cancer syndrome associated with high risk of breast and thyroid cancer. In three unrelated Japanese CS patients, three PTEN germline mutations were identified, including two novel ones: 589A → T, resulting in Lys197Stop, and 219‐222delAAGA. We also detected a previously reported mutation: 697C → T, resulting in Arg233Stop. Reports from Western countries have indicated that approximately two‐thirds of mutations are found in exons 5, 7, and 8, which is almost the same frequency as found in Japanese CS. No genotype–phenotype correlations have been found in CS patients from 21 Japanese families. © 2003 Wiley‐Liss, Inc.
Maßgeschneiderte Polyelektrolyt‐Mikrokapseln: von Multischichten zu smarten Kapseln
Authors: Peyratout Claire S. , Dähne Lars
Published: June 2004

Gegenstand dieses Aufsatzes sind neuartige Polyelektrolyt‐Mikrokapseln, einschließlich ihrer Herstellung und Eigenschaften, insbesondere im Hinblick auf ihre mechanischen und Permeationseigenschaften. Die problemlose Präparation durch einen Layer‐by‐Layer‐Selbstorganisationsprozess, die präzise Kontrolle der Wandstärke und die Flexibilität bei der Wahl der Einzelkomponenten machen die Kapseln für Anwendungen im Life‐Science‐Bereich und in den Materialwissenschaften interessant. Darüber hinaus können die Kapseln durch ein spezielles Design der inneren und äußeren Oberflächen als Mikroreaktoren für Präzipitations‐, Kristallisations‐ und Polymerisationsreaktionen und in der enzymatischen und heterogenen Katalyse verwendet werden.
Zwei Fliegen mit einer Klappe: Katalyse völlig unterschiedlicher Transformationen im Eintopfverfahren.
Authors: Ajamian Alain , Gleason James L.
Published: June 2004

Die Fortschritte in der Metallkatalyse haben die organische Synthese revolutioniert: Die Anwendung metallkatalysierter Reaktionen erstreckt sich nun über fast alle Bereiche der C‐C‐, C‐H‐ und C‐Heteroatom‐Bindungsknüpfung. Viele Jahre war die selektive Katalyse einer einzigen Transformation das Ziel der Katalysatorforschung. Mittlerweile ist jedoch das Verwenden eines einzigen Katalysators zur selektiven Vermittlung von gleich mehreren Reaktionsschritten zu einem vielversprechenden Forschungsgebiet geworden. Nachdem man sich in früheren Arbeiten auf Katalysatoren für mehrere ähnliche Transformationen konzentriert hatte, zeigten jüngste Untersuchungen, dass ein einzelner Katalysator auch mehrere sehr unterschiedliche Transformationen in einer einzigen Reaktionssequenz katalysieren kann. In diesem Kurzaufsatz werden Reaktionssequenzen mit Transformationen, die nach völlig unterschiedlichen Mechanismen ablaufen, vorgestellt.
Stabile Cyclopentine – Metalle machen's möglich!?
Authors: Rosenthal Uwe
Published: June 2004

Die Untersuchung der Grenzen für gespannte kleine cyclische Kohlenwasserstoffe ist von dauerhaftem Interesse für die chemische Forschung und führt zu Molekülen mit abnormen Geometrien und Strukturen. Beispielsweise bewirkt der Einbau von (CCCC)‐ oder (CCCC)‐Anordnungen in kleine Carbocyclen wegen der Winkeldeformation eine enorme Ringspannung; dennoch kann man solche ungewöhnlichen Strukturen erhalten, wenn man Butadiin‐ und Butatrienderivate an Zirconocenfragmente koordiniert. Dabei entstehen fünfgliedrige Metallacyclocumulene und Metallacyclopentine. Das Metallatom ist essenziell, erschwert aber eine vereinfachte Strukturbeschreibung wegen der inneren Wechselwirkungen der Metallzentren mit den Mehrfachbindungen.
Titelbild: Expanding and Shrinking Porous Modulation Based on Pillared‐Layer Coordination Polymers Showing Selective Guest Adsorption (Angew. Chem. 25/2004)
Authors: Maji Tapas Kumar , Uemura Kazuhiro , Chang Ho‐Chol , Matsuda Ryotaro , Kitagawa Susumu
Published: June 2004

Ausdehnen und Schrumpfen sind charakteristische Vorgänge der im Titelbild gezeigten porösen Säule‐Schicht‐Koordinationspolymere. Die Verformungseigenschaften belegen, dass Koordinationspolymere viel “weicher” sind als allgemein angenommen. Die Adsorptionsselektivität dieser neuen zeolithartigen Materialien lässt sich durch Wahl der organischen Säulenkomponente steuern. Näheres entnehmen Sie der Zuschrift von S. Kitagawa et al. auf S. 3331 ff.
Tailor‐Made Polyelectrolyte Microcapsules: From Multilayers to Smart Containers
Authors: Peyratout Claire S. , Dähne Lars
Published: June 2004

This review addresses the fabrication and properties of novel polyelectrolyte microcapsules, with an emphasis on their mechanical and permeability properties. Ease of preparation through layer‐by‐layer self assembly, accurate control over wall thickness as well as flexibility in the choice of constituents make these capsules very promising for numerous applications in materials and life science. Moreover, by engineering the inner and outer interfaces, these capsules can be used as microreactors for precipitation, crystallization, and polymerization reactions, as well as enzymatic, and heterogeneous catalysis.
Two Birds with One Metallic Stone: Single‐Pot Catalysis of Fundamentally Different Transformations
Authors: Ajamian Alain , Gleason James L.
Published: June 2004

Advances in metal catalysis have revolutionized organic synthesis, with the scope of metal‐catalyzed reactions now covering nearly all areas of carbon–carbon, carbon–hydrogen, and carbon–heteroatom bond formation. For years, the goal was to develop catalysts that were highly selective for a single transformation. However, a promising current area of research is the use of a single catalyst to mediate more than one transformation in a selective manner. Whereas much early work was focused on using a catalyst for several similar transformations, recent investigations have shown that it is also possible to employ a single catalyst for several very different transformations in a single reaction sequence. This Minireview focuses on methods in which the mechanisms of the transformations are fundamentally very different.
Lipid and protein loads in pupating larvae and emerging adults as affected by the composition of Mediterranean fruit fly (Ceratitis capitata) meridic larval diets
Authors: Nestel David , Nemny‐Lavy Esther , Chang Chiou Ling
Published: June 2004

The effects of sucrose and amino acid (aa) composition and concentration in meridic larval diets (e.g., partially defined at the chemical level) was examined on several parameters of Mediterranean fruit fly (Medfly) development. Lipid and protein levels of pupating larvae and emerging adults were examined. Different sucrose concentrations in the diet had small effects upon most of the development parameters. However, sucrose concentration significantly affected the ability of larvae to accumulate lipid reserves and proteins. Adults emerging from the different sucrose diets did not significantly differ in their lipid contents and protein loads. Specific deletions of aa from the diet, and general aa concentration, had a strong effect upon the parameters of development and pupating larvae lipids and proteins. Glycine‐deletion was the most deleterious, followed by the deletion of all non‐essential aa, and serine. High aa concentration in the diet has a detrimental effect upon development. Lipid contents in pupating larvae, and to some extent protein levels, were affected by aa manipulations in the diet. Lipid and protein loads in emerging adults were not significantly affected by aa manipulations. Based on the analysis of lipid frequency distribution it is suggested that the Medfly seems to regulate the level of lipid content in emerging adults within a certain range, regardless of the larval diet history or lipid contents. Proteins do not seem to be regulated as are lipids. These results point to an interesting and unexpected metabolic regulation of energetic resources during metamorphosis of the Medfly. Arch. Insect Biochem. Physiol. 56:97–109, 2004. © 2004 Wiley‐Liss, Inc.
D‐Day: geophysical investigation of a World War II German site in Normandy, France
Authors: Gaffney C. , Gater J. , Saunders T. , Adcock J.
Published: June 2004

Although military sites have long been the subject of geophysical investigation, those associated with recent military campaigns are noticeably rare. In fact, although such techniques are increasingly used to identify the unwanted legacy of modern warfare, such as unexploded ordnances or mass burials, they have not been used to investigate the archaeology of such conflict. The survey here attempts to identify the archaeology of one military site (Puits d'Herode) that was part of Hitler's Atlantic Wall and to identify the key elements associated with its D‐Day defences. Magnetic gradiometry, twin‐probe resistance and ground‐penetrating radar were used at this site and, as a result of the nature of the buried archaeology, the magnetic technique proved most valuable. Trenches and bunkers previously known from aerial photographs were located accurately and a track believed to relate to the post‐D‐Day advance of the Allied forces across Puits d'Herode was also identified. The use of geophysical data in the investigation of this site has provided a new avenue to examine previously difficult topics such as the quality of intelligence available at the time of the conflict and the level and accuracy of shelling; although these may seem unlikely targets for archaeological geophysics, they are important to military historians for whom eye witness accounts are becoming increasingly scarce. Copyright © 2004 John Wiley & Sons, Ltd.
Three‐dimensional microarray platform applied to single nucleotide polymorphism analysis
Authors: Stimpson Donald I. , Knepper Sheila M. , Shida Miho , Obata Kimimichi , Tajima Hideji
Published: June 2004

Bio‐Strand, Inc., has developed a novel DNA microarray platform utilizing a three‐dimensional (3D) DNA format. DNA probes or polymerase chain reaction (PCR) products are spotted onto a thread‐like scaffold, which is then wound onto a cylindrical core. By wrapping the thread around the core, high efficiencies are achieved in sample analysis. Using allele‐specific oligo (ASO) competitive hybridization (with Cy5 fluorescently labeled sequences), hybridized arrays are visualized using a helium–neon (HeNe) laser and quantitated/scored. The method can readily detect single nucleotide differences. We demonstrate the use of this Bio‐Strand 3D array in the analysis of a single nucleotide polymorphism (SNP). © 2004 Wiley Periodicals, Inc.
Fermentation performance of engineered and evolved xylose‐fermenting Saccharomyces cerevisiae strains
Authors: Sonderegger Marco , Jeppsson Marie , Larsson Christer , Gorwa‐Grauslund Marie‐Françoise , Boles Eckhard , Olsson Lisbeth , Spencer‐Martins Isabel , Hahn‐Hägerdal Bärbel , Sauer Uwe
Published: June 2004

Lignocellulose hydrolysate is an abundant substrate for bioethanol production. The ideal microorganism for such a fermentation process should combine rapid and efficient conversion of the available carbon sources to ethanol with high tolerance to ethanol and to inhibitory components in the hydrolysate. A particular biological problem are the pentoses, which are not naturally metabolized by the main industrial ethanol producer Saccharomyces cerevisiae. Several recombinant, mutated, and evolved xylose fermenting S. cerevisiae strains have been developed recently. We compare here the fermentation performance and robustness of eight recombinant strains and two evolved populations on glucose/xylose mixtures in defined and lignocellulose hydrolysate‐containing medium. Generally, the polyploid industrial strains depleted xylose faster and were more resistant to the hydrolysate than the laboratory strains. The industrial strains accumulated, however, up to 30% more xylitol and therefore produced less ethanol than the haploid strains. The three most attractive strains were the mutated and selected, extremely rapid xylose consumer TMB3400, the evolved C5 strain with the highest achieved ethanol titer, and the engineered industrial F12 strain with by far the highest robustness to the lignocellulosic hydrolysate. © 2004 Wiley Periodicals, Inc.
Intracellular reactive oxygen species mediate suppression of sporulation in Bacillus subtilis under shear stress
Authors: Sahoo Susmita , Krishnamurthy Rao K. , Suresh A.K. , Suraishkumar G.K.
Published: June 2004

Sporulation is an important cellular response to stress that is also significant from a bioreactor operation viewpoint. While sporulating organisms are known to show an enhanced sporulation response under several stress situations, the sporulation response to shear stress has not been investigated thus far. Such a study could be of interest since shear stress, to a greater or lesser degree, is always present in bioreactor operation. In this article, we investigate the sporulation extents of the Gram‐positive bacteria Bacillus subtilis at various defined shear levels. We show that, contrary to expectations, shear inhibits sporulation. We found an inverse correlation between the shear rate‐dependent specific intracellular reactive oxygen species level (siROS), and the sporulation extent. A 10‐fold increase in siROS resulted in about 17‐fold decrease in sporulation extent. The involvement of reactive oxygen species (ROS) in sporulation was unknown thus far. Further, through experiments that specifically increased and reduced intracellular ROS (iROS), we established that siROS is responsible for the inhibition of sporulation under shear stress. In addition, we found that shear induced siROS regulated the expression levels of the general stress proteins Ctc and σB. Based on the above, we hypothesize that siROS may regulate suppression of sporulation under high shear by altering σB and Ctc expression levels, and a model for the same is presented. © 2004 Wiley Periodicals, Inc.
Extracellular enzyme loss during polyelectrolyte flocculation of cells from fermentation broth
Authors: Pearson Carrie R. , Heng Meng , Gebert Mark , Glatz Charles E.
Published: June 2004

Association of extracellular protein product with flocculated cells reduces product yield. Here, partitioning of the enzyme subtilisin between the liquid and polyelectrolyte‐flocculated and sedimented Bacillus increased as the polymer dosage was increased beyond that necessary to obtain optimum floc character (brain floc) for cell removal by centrifugation. Partitioning to the cell floc is partly physical entrapment at all polymer dosages; however, at higher levels there is also direct interaction between the polyelectrolyte and enzyme. Enzyme loss was not likely due to pH denaturation during the flocculation process because conditions were within the stable pH range of the enzyme. The direct interaction between polyelectrolyte and enzyme was characterized through turbidimetric titrations and partitioning studies. Neither changes in the polymer feed concentration nor the method of polymer addition reduced the enzyme loss at dosages optimal for cell removal. © 2004 Wiley Periodicals, Inc.
Diffusion of lactate and ammonium in relation to growth of Geotrichum candidum at the surface of solid media
Authors: Aldarf M. , Fourcade F. , Amrane A. , Prigent Y.
Published: June 2004

Geotrichum candidum was cultivated at the surface of solid model media containing peptone to simulate the composition of Camembert cheese. The surface growth of G. candidum induced the diffusion of substrates from the core to the rind and the diffusion of produced metabolites from the rind to the core. In the range of pH measured during G. candidum growth, constant diffusion coefficients were found for lactate and ammonium, 0.4 and 0.8 cm2 day−1, respectively, determined in sterile culture medium. Growth kinetics are described using the Verlhust model and both lactate consumption and ammonium production are considered as partially linked to growth. The experimental diffusion gradients of lactate and ammonium recorded during G. candidum growth have been fitted. The diffusion/reaction model was found to match with experimental data until the end of growth, except with regard to ammonium concentration gradients in the presence of lactate in the medium. Indeed, G. candidum preferentially assimilated peptone over lactate as a carbon source, resulting in an almost cessation of ammonium release before the end of growth. On peptone, it was found that the proton transfer did not account for the ammonium concentration gradients. Indeed, amino acids, being positively charged, are involved in the proton transfer at the beginning of growth. This effect can be neglected in the presence of lactate within the medium, and the sum of both lactate consumption and ammonium release gradients corresponded well to the proton transfer gradients, confirming that both components are responsible for the pH increase observed during the ripening of soft Camembert cheese. © 2004 Wiley Periodicals, Inc.
Enhanced kinetics of genetically engineered Burkholderia cepacia: the role of vgb in the hypoxic metabolism of 2‐CBA
Authors: Urgun‐Demirtas Meltem , Pagilla Krishna R. , Stark Benjamin C.
Published: June 2004

Application of Vitreoscilla hemoglobin (VHb) technology to 2‐CBA degradation by Burkholderia cepacia strain DNT under hypoxic conditions was studied in continuous culture chemostats. Dechlorination abilities of both recombinant (VHb gene (vgb) containing) and untransformed cells were investigated at various dilution rates to ensure complete degradation of 2‐CBA. As the dilution rate increased from 0.025 to 0.25 h−1, the ratios of chloride release to degraded 2‐CBA concentration decreased from 0.95 to 0.72 and from 0.89 to 0.39 for recombinant and untransformed cells, respectively. A nonstoichiometric relationship between chloride release and 2‐CBA degradation was more pronounced for untransformed cells. Recombinant cell densities were 0.1‐0.2. g L−1 greater than untransformed cell densities for a range of dilution rates. As the dilution rate increased, the oxygen uptake rate (OUR) and the substrate utilization rate (SUR) decreased for both strains. The OUR/SUR ratio increased as the dilution rate increased for both strains but was much higher for the recombinant strain compared to untransformed cells. The specific 2‐CBA degradation rate of recombinant cells was greater than that of untransformed cells (1.17 vs. 0.46 mg CBA (mg) day−1, and half‐saturation constants for recombinant cells were lower than those of untransformed cells (0.18 and 0.32 mg CBA L−1, respectively). The pseudo‐first‐order degradation constants, k1CBA and k1ACE, were higher for recombinant cells (6.5 L (mg cells)−1 day−1 and 95.6 L (mg cells)−1 day−1, respectively) than those of untransformed cells (1.44 L (mg cells)−1 day−1 and 73.7 L (mg cells)−1 day−1, respectively). © 2004 Wiley Periodicals, Inc.
Reduction of Cr(VI) by “palladized” biomass of Desulfovibrio desulfuricans ATCC 29577
Authors: Mabbett Amanda N. , Yong Ping , Farr J. Peter G. , Macaskie Lynne E.
Published: June 2004

A novel catalytic activity of palladium [Pd(0)]‐coated cells of Desulfovibrio desulfuricans ATCC 29577 [“bio‐Pd(0)”] is demonstrated. Reduction of 700 μM Cr(VI) occurred within 24 h using formate (25 mM) or hydrogen (1 atm) as the electron donor, under conditions whereby cells lacking bound Pd(0), or palladium metal manufactured via chemical reduction of soluble Pd(II), did not reduce Cr(VI). The biomass‐bound Pd(0) also functioned in the continuous removal of 400 μM Cr(VI) from a 1 mM solution under H2 (flow residence time approximately 5 h), where chemically prepared Pd(0) was ineffective. This demonstrates a new type of active bioinorganic catalysis, whereby the presence of biomass bound to Pd(0) confers a novel catalytic capability not seen with Pd base metal or biomass alone. © 2004 Wiley Periodicals, Inc.