bluuebunny/crossref_metadata_2025 huggingface dataset:
Die Jagd auf Chinin: Etappenerfolge und Gesamtsiege
Authors: Kaufman Teodoro S. , Rúveda Edmundo A.
Published: January 2005

Die Synthese von Chinin war lange Zeit ein schwer erreichbares Ziel. Im Jahr 2004, in das der 60. Jahrestag der Veröffentlichung von Woodward und Doering über Chinin fiel, gelangen zwei neuartige, stereokontrollierte Totalsynthesen dieses Naturstoffs. Zusammen mit der ersten stereokontrollierten Totalsynthese von Chinin durch Stork 2001 belegen sie das auflebende Interesse von Organikern an der Synthese dieser Verbindung, die einst ein Wundermittel war. Diese aktuellen Veröffentlichungen über Chinin demonstrieren eindrucksvoll den immensen Fortschritt organischer Synthesemethoden während der letzten drei Jahrzehnte seit den partiell kontrollierten Chininsynthesen durch Uskokovic. Nach einem Abriss der historischen Bedeutung von Chinin als Antimalaria‐Wirkstoff und einer kurzen Schilderung der Experimente, die zu seiner Isolierung und der Aufklärung seiner Struktur beitrugen, berichten wir über die ersten Verfahren zum Aufbau und schließlich die Totalsynthesen dieses Naturstoffs.
Titelbild: Direct Observation of Hydrogen Molecules Adsorbed onto a Microporous Coordination Polymer (Angew. Chem. 6/2005)
Authors: Kubota Yoshiki , Takata Masaki , Matsuda Ryotaro , Kitaura Ryo , Kitagawa Susumu , Kato Kenichi , Sakata Makoto , Kobayashi Tatsuo C.
Published: January 2005

Grundlegende Strukturinformationen über Wasserstoffmoleküle, die in Nanokanälen adsorbiert sind, werden für das rationale Design neuartiger metall‐organischer poröser Materialien als Wasserstoffspeicher benötigt. Das Titelbild zeigt die Ladungsdichteverteilung von Wasserstoffmolekülen in den Nanokanälen eines Kupferkoordinationspolymers. Die Wasserstoffmoleküle befinden sich in den Taschen der passend dimensionierten Nanokanäle. Weitere Einzelheiten sind in der Zuschrift von Y. Kubota et al. auf S. 942 ff. zu finden.
The Quest for Quinine: Those Who Won the Battles and Those Who Won the War
Authors: Kaufman Teodoro S. , Rúveda Edmundo A.
Published: January 2005

For a long time, the synthesis of quinine constituted an elusive target. In 2004, which marked the 60th anniversary of the publication of the approach used by Woodward and Doering to synthesize quinine, two new stereocontrolled total syntheses of the natural product were accomplished. Together with the well‐publicized first stereocontrolled total synthesis of quinine by Stork in 2001, these publications evidence the revival of interest of organic chemists in the synthesis of this compound, once considered a miracle drug. The recently disclosed syntheses of quinine also testify in a remarkable manner the huge progress made by organic synthesis during the last three decades since the first series of partially controlled syntheses of quinine by the group of Uskokovic. Following an account of the historical importance of quinine as an antimalarial drug and a brief description of the experiments which contributed to its isolation and structural elucidation, the first reconstructions of quinine and the total syntheses of the natural product are discussed.
Cover Picture: Direct Observation of Hydrogen Molecules Adsorbed onto a Microporous Coordination Polymer (Angew. Chem. Int. Ed. 6/2005)
Authors: Kubota Yoshiki , Takata Masaki , Matsuda Ryotaro , Kitaura Ryo , Kitagawa Susumu , Kato Kenichi , Sakata Makoto , Kobayashi Tatsuo C.
Published: January 2005

Fundamental structural information on hydrogen molecules adsorbed in nanochannels is required for the rational synthetic design of novel metal–organic porous materials as hydrogen‐storage materials. The cover picture shows the charge‐density distribution of hydrogen molecules adsorbed in the nanochannels of a copper coordination polymer. The hydrogen molecules are located in the pocket cavities of the suitably sized nanochannels. More details can be found in the Communication by Y. Kubota et al. on page 920 ff.
Syntheses and structures of Me3Sb+CH2COO−·H2O, the monohydrate of the antimony analogue of betaine, and related compounds
Authors: Balàzs Gàbor , Balàzs Lucia , Breunig Hans J. , Lork Enno
Published: January 2005

The syntheses of the antimony analogue of betaine, Me3Sb+CH2COO− (1), of the precursor [Me3SbCH2COOH][Br] (2) and of [Me3SbCH2COOCH2CH3][Br] (3) are reported. A new method for the synthesis of solvent‐free Me3Sb is described. The structures of 1·H2O and 3 were determined by single crystal X‐ray diffractometry. Copyright © 2002 John Wiley & Sons, Ltd.
Synthesis of unsymmetric diynes by palladium and cesium fluoride catalyzed coupling of terminal bromoalkynes with alkynylstannane
Authors: Ābele Edgars , Rubina Kira , Fleisher Mendel , Popelis Juris , Arsenyan Pavel , Lukevics Edmunds
Published: January 2005

The Stille reaction of unsymmetric diynes from terminal bromoalkynes with alkynylstannane in the presence of palladium catalyst and cesium fluoride was studied. The system (bromoalkyne: PhC≡CSnMe3:Pd2(dba)3:PPh3:CsF:18‐crown‐6) = (1:1:0.015:0.06:2.2:0.1) in toluene at reflux temperature was found to be the most favored. Products were obtained in 31–100% yields. Correlations between calculated electron density, dipole moments and 13C NMR spectral data of synthesized bromoacetylenes and diynes have been carried out. Copyright © 2002 John Wiley & Sons, Ltd.
Metallocenyl‐[2H]naphtho[1,2‐b]pyrans: metal effect on the photochromic behaviour
Authors: Brun Pierre , Guglielmetti Robert , Anguille Stéphane
Published: January 2005

Previous studies have shown that the substitution by a ferrocenyl group in the 2‐position of naphthopyrans has a specific and an original effect on the photochromic behaviour. In this work, the synthesis and the photochromic properties of new naphthopyrans substituted in the 2‐position by three different metallocenyl groups (ferrocenyl, ruthenocenyl and osmocenyl) are presented. Whereas the ferrocenyl‐substituted derivatives under UV irradiation show two absorption bands, the ruthenocenyl and osmocenyl derivatives are characterized by only one absorption band under the same condition. The photochromic behaviour of these compounds is compared with that of their parent alkyl or phenyl 2‐substituted [2H]‐naphtho[1,2‐b]pyrans. Copyright © 2002 John Wiley & Sons, Ltd.
Selected radar images of man‐made underground galleries
Authors: Lorenzo H. , Hernández M. C. , Cuéllar V.
Published: January 2005

Ground‐penetrating radar (GPR), as a high‐resolution geophysical prospecting method, has proved to be a very useful tool in archaeological site investigations, especially in the detection and identification of tunnels and galleries. This work shows seven selected profiles collected at four different archaeological sites in Spain and Mexico, with a wide variety of targets, not only in terms of their size (from 1 × 1 m to 3 × 4 m) but also in their depth (from 0.5 to 7 m). In all, 14 galleries and/or tunnels were detected. The approach to these studies was organized in two ways: firstly the presence of a known subsoil was used to compare the response of different antennae looking for these kinds of targets; secondly, GPR was used to find unknown historical galleries before any excavation took place. The equipment used in these studies were the SIR‐8, with 120 and 500 MHz monostatic antennae, and PulseEkko IV, with 100 MHz bistatic antennae. Copyright © 2002 John Wiley & Sons, Ltd.
Archaeogeophysical investigations around the Bilge Qagan monument in Khosho Tsaidam, Mongolia
Authors: Ates Abdullah
Published: January 2005

Ancient Turkish monuments in Mongolia are historically important owing to the earliest Turkish and Chinese inscriptions written on them. In this paper, magnetic and conductivity meter surveys conducted in the vicinity of the Bilge Qagan monument are presented. Magnetic and conductivity maps show rectangular shaped anomalies, which could be caused by a buried wall‐like structure or floor tiles to protect the Bilge Qagan monument. The Altar Stone, which is also described as a base for a pagoda, gives a strong magnetic anomaly. This anomaly is processed by advanced geophysical methods and it is demonstrated that the actual rock body has some form of remanent magnetization, which causes the magnetic anomaly. By means of conductivity surveying, it also can be suggested that the near‐surface formations have significant water content. Copyright © 2002 John Wiley & Sons, Ltd.
Random rates of growth and return: introducing the expo‐normal distribution
Authors: de La Grandville Olivier , Pakes Anthony G. , Tricot Claude
Published: January 2005

Expected values and standard deviations of the geometric means of independent positive random variables are useful indicators of the long‐term profitability of an investment, or survival of a biological population. Often these quantities cannot be evaluated in a closed form, or even if they can, there may be a choice between several probability models for the ‘annual’ growth factors. This paper formulates approximations for geometric means and standard deviations. It evaluates their performance and compares the best of them with the exact values for selected probability models of the annual factors. Among these is a new model for annual log‐returns, called the expo‐normal law. This is the law of log X, where X has a normal law conditioned on X>0. Its properties are developed in some detail.

It is found that for the ranges of annual means and standard deviations typically encountered in financial applications, the longer horizon values depend little on the choice of probability model, and that, where possible, exact evaluation is computationally simpler than using approximations. Copyright © 2002 John Wiley & Sons, Ltd.
Development and validation of a non‐linear IVIVC model for a diltiazem extended release formulation
Authors: Sirisuth Nattee , Augsburger Larry L. , Eddington Natalie D.
Published: January 2005

To develop and validate internally an in vitro–in vivo correlation (IVIVC) for a diltiazem multi‐particulate bead extended release formulation. In vitro dissolution of diltiazem capsules was examined using the following methods: USP Apparatus II (paddle) at 100 rpm and USP Apparatus III at 30 dpm. Seven healthy subjects received three diltiazem formulations (90 mg): slow (S), moderate (M), fast (F) releasing and an oral solution (90 mg). Serial blood samples were collected over 48 h and analyzed by a validated HPLC assay using ultraviolet detection. The f2 metric (similarity factor) was used to analyze the dissolution data. Linear and non‐linear (quadratic, cubic, and sigmoid functions) correlation models were developed using pooled fraction dissolved (FRD) and fraction absorbed (FRA) data from various combinations of the formulations. Predicted diltiazem concentrations were obtained by convolution of the in vivo dissolution rates. Prediction errors were estimated for Cmax and AUC to determine the validity of the correlation.

Apparatus II using purified water was found to be the most discriminating dissolution method. Significant intersubject (CV%>50) was observed for Cmax and AUC. The quadratic M/F IVIVC model provided a significant relationship between FRD and FRA when using either two or three of the formulations. An average percent prediction error for Cmax and AUC for all formulations was 12.4% and 9.2%, respectively.

The prediction errors observed for Cmax and AUC suggest that the predictability of the quadratic IVIVC model is inconclusive, as such, external validation studies are required. Copyright © 2002 John Wiley & Sons, Ltd.
Pharmacokinetics of controlled‐release verapamil in healthy volunteers and patients with hypertension or angina
Authors: Gupta Suneel , Modi Nishit B. , Sathyan Gayatri , Ho Pai‐ling , Aarons Leon
Published: January 2005

Aims: To study the dose‐ranging population pharmacokinetics of controlled release verapamil in healthy subjects and patients with angina or hypertension. To characterize the pharmacodynamics of controlled‐release verapamil in patients with hypertension.

Methods: Dose‐ranging studies were conducted in healthy volunteers and patients with hypertension and angina. Subjects received doses of 120, 180, 360, or 540 mg racemic verapamil as an osmotic controlled‐release formulation. A population pharmacokinetic model involving zero‐order release of verapamil into the gastrointestinal tract with first‐order absorption and elimination was used to describe the steady‐state plasma concentration profile for R‐ and S‐verapamil. A population sigmoid Emax pharmacodynamic model was used to describe the effect of R‐ and S‐verapamil on mean arterial blood pressure.

Results: S‐verapamil had an approximate 4‐fold greater apparent clearance than R‐verapamil in both healthy volunteers and patients. The apparent plasma clearance of R‐ and S‐verapamil in healthy volunteers decreased over the dose range of 120–540 mg. A similar dose‐dependent decrease in apparent plasma clearance was also noted in patients. None of the patient demographic variables examined (age, total body weight, lean body weight, body mass index, and height) explained the variability in verapamil pharmacokinetics. The pharmacodynamic model describing the relationship between verapamil plasma concentration and mean arterial blood pressure indicated that the S‐verapamil had a 3.6‐fold lower estimated EC50 compared to R‐verapamil.

Conclusions: The results from this dose‐ranging pharmacokinetic investigation in healthy volunteers and patients are consistent with previous reports in healthy subjects. S‐verapamil is cleared more rapidly than R‐verapamil and the estimated EC50 for S‐verapamil was 3.6‐fold lower than for R‐verapamil. Estimated EC50 values for R‐ and S‐verapamil decreased with increasing age and decreasing weight. Copyright © 2002 John Wiley & Sons, Ltd.
Influence of fluconazole on the pharmacokinetics of omeprazole in healthy volunteers
Authors: Kang Byoung C. , Yang Chang Q. , Cho Hae K. , Suh Ok K. , Shin Wan G.
Published: January 2005

Influence of fluconazole on the pharmacokinetics of omeprazole was evaluated by single oral administration of omeprazole capsule 20 mg (control group), or single oral administration of fluconazole capsule, 100 mg, and omeprazole, 20 mg, after 4 days of daily oral administration of fluconazole, 100 mg (treated group), to 18 healthy male volunteers. Omeprazole is extensively metabolized in the liver through 5‐hydroxylation and sulfoxidation reactions catalyzed predominantly by CYP2C19 and CYP3A4, respectively. Fluconazole is a potent competitive inhibitor of CYP2C19 and a weak inhibitor of CYP3A4. In treated group, the area under the plasma concentration–time curve of omeprazole from time zero to time infinity (AUC) was significantly greater (3090 vs 491 ng h/ml), terminal half‐life of omeprazole was significantly longer (2.59 vs 0.85 h), and peak plasma concentration of omeprazole (Cmax) was significantly higher (746 vs 311 ng/ml) than that in control group. The greater AUC and higher Cmax in treated group could be due to inhibition of omeprazole metabolism by fluconazole. Copyright © 2002 John Wiley & Sons, Ltd.
A study of streptomycin blood level information of patients undergoing hemodialysis
Authors: Akaho Eiichi , Maekawa Takashi , Uchinashi Masako , Kanamori Ryuichi
Published: January 2005

Pharmacokinetic feature of streptomycin (SM) was investigated before and during hemodialysis (HD) in four patients with renal failure undergoing HD. SM concentrations were assayed by using TDX SM KIT (DAINABOT). Patients received 10 mg/kg of SM by intramuscular injection before HD.

Pharmacokinetic parameters of SM intramuscular injection before HD were ka=2.38±0.53 h−1; ke=0.0130±0.0025 h−1; Vd=0.313±0.026l/kg and t1/2=55.6±10.4 h.

The maximum concentration (Cmax) of SM was observed at about 2 h after the SM administration and the mean serum concentration of SM was 30.4 µg/ml; even 4 h after the SM injection, the concentration still remained in a range over 30 µg/ml. The data suggest that a possible toxicity might have appeared in the patients.

During the hemodialysis an average t1/2 value was 3.32 h. This value is close to the value of a healthy person. The ke value of patient A during the hemodialysis became 24 times as large as that observed before the hemodialysis. On the average it was 17 times as large as that observed before the hemodialysis. Thus, it was found that the values of pharmacokinetics parameters such as ke and t1/2 during the hemodialysis were similar to those of a healthy person, although there are some variations. Copyright © 2002 John Wiley & Sons, Ltd.
Pharmacokinetics and dose proportionality of BMS‐204352 after intravenous administration to dogs
Authors: Krishna Rajesh , Shah Vinod R. , Mantha Subbaro , Vachharajani Nimish N. , Srinivas Nuggehally
Published: January 2005

BMS‐204352 is a novel maxi‐K channel opener that is being developed for the treatment for stroke. The current study was designed to evaluate the dose proportionality and pharmacokinetics of BMS‐204352 in dogs. In an open, three‐way crossover study, three beagle dogs received a single intravenous dose of BMS‐204352 as a 6‐min infusion into the femoral vein at 0.4, 0.9, and 2.0 mg/kg dose levels. There was at least a 1‐week washout period between treatments. Serial blood samples were collected for up to 32 h post dose and plasma samples were analyzed for the concentrations of intact BMS‐204352 using a validated liquid chromatographic mass spectrometric (LC/MS) method. Pharmacokinetic analysis was performed using a non‐compartmental method. Results indicated that peak BMS‐204352 concentrations (Cmax) and area under the plasma concentration–time curves (AUC) values increased in a dose proportional manner. Mean residence time (MRT, 18.2–21.9 h) and elimination half‐life (Thalf, 13.5–17 h) did not change with dose. There was no dose dependency in the mean BMS‐204352 total body clearance (CLT, 134–158 ml/h/kg) and mean steady state volume of distribution (VSS, 2839‐3291 ml/kg). The high VSS value indicated that BMS‐204352 was distributed extensively in the extravascular tissues. In conclusion, BMS‐204352 exhibits linear pharmacokinetics over the dose range tested (0.4–2 mg/kg). Copyright © 2002 John Wiley & Sons, Ltd.
Minimal effect of ketoconazole on cyclosporine (SangCyATM) oral absorption and first‐pass metabolism in rats: evidence of a significant vehicle effect on SangCyA absorption
Authors: Wong Susan , Wong Harrison T. , Wacher Vincent J.
Published: January 2005

The current work evaluated the effect of the CYP3A inhibitor ketoconazole on the oral absorption and first‐pass metabolism of cyclosporine administered as the SangCyA formulation. Groups of 6 male Sprague–Dawley rats were administered SangCyA (5 and 15 mg/kg) by oral gavage alone and with ketoconazole (30 mg/kg). Blood cyclosporine levels were measured over 6 h, encompassing the cyclosporine absorption window. A significant vehicle effect on SangCyA absorption was observed. Comparing a 15 mg/kg dose, cyclosporine Cmax (mean±SD 1.12±0.16 µg/ml) and AUC0−6 (5.34±0.71 µg h/ml) were 50% lower when propylene glycol was used as gavage vehicle instead of saline (2.19±0.94 µg/ml and 9.52±2.52 µg h/ml, respectively). Coefficients‐of‐variation for these parameters were halved in the propylene glycol vehicle however Tmax was unaffected. Ketoconazole increased cyclosporine Cmax and AUC0−6 by 50–60%, regardless of the vehicle or the cyclosporine dose, without altering Tmax (2–3 h). The small effect of ketoconazole suggests that CYP3A‐mediated intestinal and first‐pass hepatic metabolism are minor determinants of cyclosporine oral bioavailability in rats. Copyright © 2002 John Wiley & Sons, Ltd.
Pharmacokinetics of a novel surface‐active agent, purified poloxamer 188, in rat, rabbit, dog and man
Authors: Grindel J. Michael , Jaworski Ted , Emanuele R. Martin , Culbreth Paula
Published: January 2005

Purified poloxamer 188 (PP188) is a non‐ionic, block copolymer surfactant that is currently being evaluated clinically in sickle cell disease vaso‐occlusive crisis and acute chest syndrome and preclinically in spinal cord injury and muscular dystrophy. This paper describes the pharmacokinetics of PP188 in rats, pregnant rats, pregnant rabbits, dogs and humans. Plasma protein binding interaction studies demonstrated no clinically significant effects on narcotic analgesics, hydroxyurea, warfarin, diazepam or digitoxin, but an increase in free fraction for propranolol. The plasma concentrations increased proportionate with increasing dose in all species tested. Renal clearance accounted for 90% of total plasma clearance in man. A single metabolite was detected and quantified in the plasma from dogs and humans that was cleared more slowly than parent drug. Allometric scaling of plasma clearance and volume of distribution at steady‐state (Vss) across species provided good predictions of the pharmacokinetic parameters in humans. Based on the comparative pharmacokinetics of PP188 in rat, rabbit, dog and man, all three animal species were appropriate models for evaluating various aspects of PP188's toxicological profile. Copyright © 2002 John Wiley & Sons, Ltd.
Pharmacokinetic changes of diltiazem and desacetyldiltiazem after oral administration of diltiazem in rabbits with diabetes mellitus induced by alloxan
Authors: Choi Jun S. , Kim Yoon G.
Published: January 2005

Physiological changes occurring in diabetes mellitus patients could alter the pharmacokinetics of drugs used to treat hypertension resulting from diabetic complications. Hence, the pharmacokinetics of diltiazem (DTZ) and its metabolite, desacetyldiltiazem (DAD), were investigated after oral administration of DTZ. DTZ, 20 mg/kg, was orally administered to control rabbits and rabbits with fifth day (experiment was performed at fifth day after first and second days intravenous administration of alloxan) and 13th day (experiment was performed at 13th day after first, second, sixth, and 10th days intravenous administration of alloxan) diabetes mellitus induced by alloxan. Impaired kidney and liver functions were observed in both diabetic groups based on plasma chemistry data and/or tissue microscopy. After oral administration of DTZ, the area under the plasma concentration–time curve from time zero to time infinity were 767, 1280 and 1550 ng h/ml for control rabbits and fifth and 13th days diabetes mellitus rabbits, respectively. The values in diabetes mellitus rabbits were significantly different as compared to control rabbits. The terminal half‐lives of DTZ were significantly longer in fifth (13.4 h) and 13th (13.0 h) days diabetes mellitus rabbits than that in control rabbits (8.76 h). The renal clearances of DTZ in fifth (0.316 l/h/kg) and 13th (0.264 l/h/kg) days diabetes mellitus rabbits were significantly slower than that in control rabbits (0.505 l/h/kg), and this could be due to impaired kidney function in the diabetes mellitus rabbits. However, other pharmacokinetic parameters of DAD were not significantly different among three groups of rabbits. Copyright © 2002 John Wiley & Sons, Ltd.
Determinants of the magnitude of willingness to accept relative to willingness to pay
Authors: Shefrin Hersh , Caldwell David
Published: January 2005

In this paper we test two hypotheses that stem from the work of Mellers, Chang, Birnbaum and Ordonez (1992). The first hypothesis is that in a binary gamble, the ratio of WTA to WTP is decreasing in the probability attached to a nonzero event. The second hypothesis is that this ratio is independent of the size of stakes. We find support for the first hypothesis, but mixed support for the second. The second hypothesis holds in the case of gains, but not in the case of losses. Copyright © 2001 John Wiley & Sons, Ltd.
Relating individual differences in Attitude toward Ambiguity to risky choices
Authors: Lauriola Marco , Levin Irwin P.
Published: January 2005

Subjects (76 adult Italians of varying ages) completed a two‐part procedure. One part used an Ellsberg‐type task which allowed for both aggregate and individual level analysis of Attitude toward Ambiguity. The other part used an expanded risky choice task to assess the same subjects' Attitude toward Risk. While there was an overall tendency for subjects to be slightly ambiguity‐averse, there was a positive correlation between Attitude toward Ambiguity and Attitude toward Risk. This relation was particularly strong when the risky choice was to avoid a loss rather than to achieve a gain. Copyright © 2001 John Wiley & Sons, Ltd.
Averaging probability judgments: Monte Carlo analyses of asymptotic diagnostic value
Authors: Johnson Timothy R. , Budescu David V. , Wallsten Thomas S.
Published: January 2005

Wallsten et al. (1997) developed a general framework for assessing the quality of aggregated probability judgments. Within this framework they presented a theorem regarding the effects of pooling multiple probability judgments regarding unique binary events. The theorem states that under reasonable conditions, and assuming conditional pairwise independence of the judgments, the average probability estimate is asymptotically perfectly diagnostic of the true event state as the number of estimates pooled goes to infinity. The purpose of the present study was to examine by simulation (1) the rate of convergence of averaged judgments to perfect diagnostic value under various conditions and (2) the robustness of the theorem to violations of its assumption that the covert probability judgments are conditionally pairwise independent. The results suggest that while the rate of convergence is sensitive to violations of the conditional pairwise independence, the asymptotic properties remain relatively robust under a large variety of conditions. The practical implications of these results are discussed. Copyright © 2001 John Wiley & Sons, Ltd.
Promoting fluency of performance of self‐help tasks with a person with multiple disabilities
Authors: Lancioni Giulio E. , O'Reilly Mark F. , Campodonico Francesca
Published: January 2005

A combination of favorite songs and verbal prompts (automatically delivered through portable technology) was used to promote fluency of performance of self‐help tasks in a young man with multiple disabilities. Data indicated that the intervention was effective in reducing the time required by the man to complete the self‐help tasks (dressing and washing). A momentary withdrawal of the prompts after about 6 months from the beginning of the study was accompanied by performance deterioration. Implications of the findings are discussed. Copyright © 2002 John Wiley & Sons, Ltd.
The effects of the Positive Environment Program (PEP) on the behaviors of adults with profound cognitive and physical disabilities
Authors: Realon Rodney E. , Bligen Richard A. , La Force Anne , Helsel William J. , Goldman Vinston
Published: January 2005

This study evaluated the effects of the Positive Environment Program (PEP) on the behaviors of residents and staff in a state‐operated residential facility during a 2½ year period. The participants included 19 adult residents with profound cognitive and physical disabilities and 11 staff members who worked with them. Data were collected on alertness, leisure material availability, engagement, staff interactions, and resident affect during two samples of data collection six months prior to implementation of PEP. Training was then provided to staff on positive interaction skills. Following the training, researchers implemented a monitoring program and a staff incentive program. The results of this project showed improvements in staff interactions, resident interaction with leisure materials, improved levels of alertness, and increases in a ‘happiness index’. The benefits and limitations of this project as well as future research are discussed. Copyright © 2002 John Wiley & Sons, Ltd.
Decreasing rumination using a starchy food satiation procedure
Authors: Dudley Laura L. , Johnson Cammarie , Barnes R. Scott
Published: January 2005

A starchy food satiation procedure was evaluated in an ABAB withdrawal design on the post‐meal rumination of a nine‐year‐old girl with autism. During treatment unlimited quantities of starchy foods were provided following each meal. High rates of rumination occurred during baseline conditions, followed by an immediate decrease in rumination during treatment. Rumination decreased to 82 and 97% of baseline during the first and second treatment conditions, respectively. In addition, follow‐up probes were conducted at irregular intervals for 4 years following treatment, during which zero or near‐zero rates of rumination were sustained. This study extends the literature on the functional relation between increased starchy food quantity and rumination in adults to rumination with a young child, and demonstrates maintenance of the treatment effect for 4 years. Copyright © 2002 John Wiley & Sons, Ltd.
Collateral effects of behavioral parent training on families of children with developmental disabilities and behavior disorders
Authors: Feldman Maurice A. , Werner Shannon E.
Published: January 2005

We evaluated collateral effects of behavioral parent training (BPT) on families with children who have developmental disabilities and behavior disorders. We compared 18 BPT graduates to 18 similar families waiting for service. The BPT graduates reported significantly less (i) child behavior problems, (ii) disruption to child and family quality of life due to child problem behavior, and (iii) stress related to limits on family opportunities and child physical limitations, up to 5 years after discharge. On a self‐efficacy scale, the graduates reported being more effective child behavior change agents in not only stopping child problem behavior, but also in preventing new occurrences and teaching the child appropriate behavior. These results suggest that BPT has persistent beneficial effects on children and parents. The findings reflect the program's focus on teaching parents how to use functional assessment derived positive teaching strategies to replace child problem behavior. Copyright © 2002 John Wiley & Sons, Ltd.
Rapid expression of vaccine proteins for B‐cell lymphoma in a cell‐free system
Authors: Yang Junhao , Kanter Gregory , Voloshin Alexei , Michel‐Reydellet Nathalie , Velkeen Hendrik , Levy Ronald , Swartz James R.
Published: January 2005

The idiotype (Id)‐granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) fusion proteins are potential vaccines for immunotherapy of B‐cell lymphoma. In this study, four vaccine candidates were constructed by fusing murine GM‐CSF to the amino‐ or carboxy‐terminus of the 38C13 murine B‐lymphocyte Id scFv with two different arrangements of the variable regions of the heavy chain and light chain (VL‐VH and VH‐VL). scFv (VH‐VL) and GM‐CSF/scFv fusion proteins were expressed in an Escherichia coli cell‐free protein synthesis system. In order to promote disulfide bond formation during cell‐free expression, cell extract was pretreated with iodoacetamide (IAM), and a sulfhydryl redox buffer composed of oxidized and reduced glutathione was added. The E. coli periplasmic disulfide isomerase, DsbC, was also added to rearrange incorrectly formed disulfide linkages. The 38C13 B‐lymphocyte Id scFv was expressed with 30% of its soluble yield in active form (43 μg/ml) when tested with an anti‐idiotypic mAb, S1C5, as the capture antibody in radioimmunoassay. It was found that the amino‐terminal GM‐CSF fusion proteins, GM‐VL‐VH and GM‐VH‐VL, showed much higher activity than the carboxy‐terminal GM‐CSF fusion proteins, VL‐VH‐GM and VH‐VL‐GM, in stimulating the cell proliferation of a GM‐CSF‐dependent cell line, NFS‐60. Between the two amino‐terminal GM‐CSF fusion proteins, GM‐VL‐VH showed a higher total and soluble yield than GM‐VH‐VL. © 2005 Wiley Periodicals, Inc.
Selection of high‐producing CHO cells using NPT selection marker with reduced enzyme activity
Authors: Sautter Kerstin , Enenkel Barbara
Published: January 2005

We developed an expression system that aimed to increase the proportion of high producers in a transfected cell population in order to reduce the effort in clone screening. The principle is based on the impairment of the selection marker. Twelve single‐point mutations in more or less conserved domains of the resistance marker gene neomycin‐phosphotransferase (NPT) resulted in different degrees of reduced enzyme activity, depending on the amino acid conservation and the kind of amino acid exchange. In all transfected, mutant‐NPT bearing CHO‐DG44 cell pools surviving the selection with G418, the ratio of high‐producing cells to total cell number was higher than in pools selected with wildtype‐NPT. Furthermore, these pools showed, in comparison to wildtype‐NPT selected pools, not only higher NPT‐RNA levels but also increased specific productivities and higher titers of a coexpressed biopharmaceutically relevant product. Elevated productivity could be ascribed to higher gene copy numbers, integration into chromatin regions with higher transcriptional activity, or a combination of both effects. Thus, the use of NPT‐mutants as selection markers is suitable for the enrichment of high producers in a transfected CHO‐DG44 cell population, since cell survival is achieved only if the enzymatic impairment of the cointegrated resistance marker is compensated by a higher expression level. © 2005 Wiley Periodicals, Inc.
Riboflavin‐ and cobalamin‐mediated biodegradation of chloroform in a methanogenic consortium
Authors: Guerrero‐Barajas Claudia , Field Jim A.
Published: January 2005

Chloroform (CF) is an important priority pollutant contaminating groundwater. Reductive dechlorination by anaerobic microorganisms is a promising strategy towards the remediation of CF. The objective of this study was to evaluate the use of redox active vitamins as electron shuttles to enhance the anaerobic biodegradation of CF in an unadapted methanogenic consortium not previously exposed to chlorinated compounds. Only negligible degradation of CF was observed in control cultures lacking redox active vitamins. The addition of riboflavin (RF), cyanocobalamin (CNB12), and hydroxycobalamin (HOB12) enabled biodegradation of CF. The reactions were predominantly catalyzed biologically as evidenced by the lack of any CF conversion in heat‐killed controls amended with the cobalamins or minor conversion with RF. In live cultures, significant increases in the rate of CF conversion was observed at substoichiometric molar ratios as low as 0.1 to 0.01 vitamin:CF for RF and CNB12, respectively. At the highest molar vitamin:CF ratios tested of 0.2, the first‐order rate constant of CF degradation was 5.3‐ and 91‐fold higher in RF and CNB12 amended cultures, respectively, compared to the unamended control culture. The distribution of biotransformation products was highly impacted by the type of redox active vitamin utilized. Cultures supplemented with RF provided high yields of dichloromethane (DCM). On the other hand, cobalamins promoted the near complete mineralization of organochlorine in CF to inorganic chloride and lowered the yield of DCM. In cultures where no or little CF bioconversion occurred, prolonged exposure to CF resulted in cell lysis, as evidenced by the release of intracellular chloride. The results taken as a whole suggest that the anaerobic bioremediation of CF‐contaminated sites can greatly be improved with strategies aimed at increasing the concentration of redox active vitamins. © 2005 Wiley Periodicals, Inc.
Effect of oxygen on the Escherichia coli ArcA and FNR regulation systems and metabolic responses
Authors: Shalel Levanon Sagit , San Ka‐Yiu , Bennett George N.
Published: January 2005

Escherichia coli has several elaborate sensing mechanisms for response to the availability of oxygen and the presence of other electron acceptors. The adaptive responses are coordinated by a group of global regulators, which include the one‐component Fnr protein, and the two‐component Arc system. To quantitate the contribution of Arc and Fnr‐dependent regulation in catabolism, arcA and fnr mutant strains were constructed using the recently developed lambda derived recombination system. The metabolic activity of wildtype E. coli, an arcA mutant, an fnr mutant, and a double arcA‐fnr mutant, via the fermentative pathways in glucose‐limited cultures and different oxygen concentrations was studied in chemostat cultures at steady state. It was found that the most significant role of ArcA is under microaerobic conditions, while that of FNR is under more strictly anaerobic conditions. The FNR protein is normally inactive during microaerobic conditions. However, our results indicate that in the arcA mutant strain the cells behave as if a higher level of the FNR regulator is in the activated form compared to the wildtype strain during the transition from aerobic to microanaerobic growth. The results show a significant increase in the flux through pyruvate formate lyase (PFL) in the presence of oxygen. The activity of FNR‐regulated pathways in the arcA mutant strain is correlated with the high redox potential obtained under microaerobic growth. © 2005 Wiley Periodicals, Inc.
Use of hepatectomy and splenectomy to treat hepatocellular carcinoma with cirrhotic hypersplenism
Authors: Chen X-P , Wu Z-D , Huang Z-Y , Qiu F-Z
Published: January 2005

Background

The aim of this study was to compare the outcome after simultaneous hepatectomy and splenectomy with that after hepatectomy alone for hepatocellular carcinoma with associated hypersplenism.

Methods

Two hundred and four patients with hepatocellular carcinoma and cirrhotic hypersplenism were divided non-randomly into two groups. Ninety-four underwent simultaneous hepatectomy and splenectomy and 110 underwent hepatectomy alone. White blood cell (WBC) and platelet counts, total serum bilirubin levels, immune function, incidence of complications and 5-year survival rates in the two groups were compared.

Results

WBC and platelet counts, distribution of T cell subsets, and levels of bilirubin, interferon γ and interleukin 2 were different between the two groups after operation. All patients who underwent hepatectomy and splenectomy but only 15·5 per cent of those who had hepatectomy alone completed adjuvant chemotherapy. The 5-year tumour-free survival rate was significantly higher after hepatectomy and splenectomy than after hepatectomy alone (37 versus 27·3 per cent; P = 0·003), although overall survival rates were similar.

Conclusion

Simultaneous hepatectomy and splenectomy was associated with improved 5-year tumour-free survival in patients with hepatocellular carcinoma and hypersplenism.
Sequential cohort study of Dacron® patch closure following carotid endarterectomy
Authors: Ali T , Sabharwal T , Dourado R A , Padayachee T S , Hunt T , Burnand K G
Published: January 2005

Background

Carotid endarterectomy reduces the risk of stroke and death in patients with severe carotid artery stenosis. This study examined whether the technique used to close the arteriotomy influenced the rate of perioperative transient ischaemic attack (TIA), stroke or death.

Methods

A cohort of 236 patients undergoing carotid endarterectomy at a single centre was studied; 117 patients had primary closure of the arteriotomy and 119 patients in a sequential series had closure with a Dacron® patch. A standard endarterectomy with completion intraoperative duplex imaging and digital subtraction angiography was used throughout.

Results

Patch closure was associated with a significant reduction in the 30-day combined death, stroke and TIA rate: 10·3 per cent for primary closure versus 2·5 per cent for patch closure (P = 0·017). The risk of any cerebral event (stroke or TIA) was also significantly reduced (7·7 versus 1·7 per cent; P = 0·033). Residual stenosis on completion angiography was more common after primary closure (24·6 versus 7·4 per cent; P = 0·003).

Conclusion

Dacron® patch closure had a higher technical success rate on completion imaging and was associated with a significant reduction in the risk of perioperative stroke, TIA and death.
Gastrointestinal complications after cardiac surgery
Authors: Andersson B , Nilsson J , Brandt J , Höglund P , Andersson R
Published: January 2005

Background

Gastrointestinal complications after cardiac surgery are often difficult to diagnose, and are associated with high morbidity and mortality rates. The aim of this study was to determine risk factors for these complications.

Method

Between 1996 and 2001 data were collected prospectively from 6119 patients who underwent 6186 cardiac surgical procedures. Data from patients who experienced major gastrointestinal complications were analysed retrospectively by univariate and multivariate analysis.

Results

Fifty major gastrointestinal complications were identified in 47 patients (incidence 0·8 per cent). Thirteen of these patients died within 30 days. The most common complication was upper gastrointestinal bleeding (16 patients). Intestinal ischaemia was the most lethal complication (eight of ten patients died). Abdominal surgical operations were performed in 12 patients. Multivariate analysis identified nine variables that independently predicted major gastrointestinal complications: age over 80 years, active smoker, need for preoperative inotropic support, New York Heart Association class III–IV, cardiopulmonary bypass time more than 150 min, postoperative atrial fibrillation, postoperative heart failure, reoperation for bleeding and postoperative vascular complications.

Conclusion

Nine risk factors for the development of major gastrointestinal complications after cardiac surgery were identified. Gastrointestinal complications were often lethal but did not independently predict death within 30 days.
In-contiguity and non-anatomical extension of right hepatic trisectionectomy for liver metastases
Authors: Lodge J P A , Menon K V , Fenwick S W , Prasad K R , Toogood G J
Published: January 2005

Background

In some patients undergoing right hepatic trisectionectomy for metastases, extension of the resection beyond the falciform ligament is necessary to achieve tumour clearance. The aim of the present study was to assess the early and long-term outcomes and hepatic function in patients who underwent extensive liver resection beyond right trisectionectomy.

Methods

Thirty-eight patients who had extension of a right trisectionectomy, either in contiguity (IC) or in a non-anatomical (NA) fashion, for liver metastases were included in the study. In-hospital mortality, hepatic function and other morbidity were recorded. Survival outcomes were analysed for the subgroup of patients with colorectal liver metastases. The clinical risk score described by the Memorial Sloan–Kettering Cancer Center was applied to all patients with colorectal liver metastases.

Results

Sixteen patients had IC resection, 15 NA resection, and seven had both IC and NA procedures. There was one in-hospital death. Hepatic dysfunction was seen in 25 patients and two developed liver failure. Disease-free actuarial 3-year survival was 42 per cent for patients with colorectal liver metastases. Survival was significantly better in patients with a clinical risk score of 3 or less.

Conclusion

Extension of right trisectionectomy for liver metastases was associated with a low risk of death and hepatic failure.
Liver resection for hepatocellular carcinoma in patients with cirrhosis
Authors: Wu C-C , Cheng S-B , Ho W-M , Chen J-T , Liu T-J , P'eng F-K
Published: January 2005

Background

Although liver resection is now a safe procedure, its role for hepatocellular carcinoma (HCC) in patients with cirrhosis remains controversial.

Methods

This study compared the results of liver resection for HCC in patients with cirrhosis over two time intervals. One hundred and sixty-one patients had resection during period 1 (1991–1996) and 265 in period 2 (1997–2002). Early and long-term results after liver resection in the two periods were compared, and clinicopathological characteristics that influenced survival were identified.

Results

Tumour size was smaller, indocyanine green retention rate was higher, patients were older and a greater proportion of patients were asymptomatic in period 2 than period 1. Operative blood loss, need for blood transfusion, operative mortality rate, postoperative hospital stay and total hospital costs were significantly reduced in period 2. The 5-year disease-free survival rates were 28·2 and 33·9 per cent in periods 1 and 2 respectively (P = 0·042), and 5-year overall survival rates were 45·9 and 61·2 per cent (P < 0·001). Multivariate analysis identified serum α-fetoprotein level, need for blood transfusion and Union Internacional Contra la Cancrum tumour node metastasis stage as independent determinants of disease-free and overall survival.

Conclusion

The results of liver resection for HCC in patients with cirrhosis improved over time. Liver resection remains a good treatment option in selected patients with HCC arising from a cirrhotic liver.
Pancreatic trauma in children
Authors: Stringer M D
Published: January 2005

Background

Pancreatic trauma is rare in children, and management strategies are diverse and controversial. The aim of this study was to report the outcome of a consecutive series of children with pancreatic injury seen at a single regional centre over a decade.

Methods

All children under 14 years of age referred with pancreatic injury between January 1995 and June 2004 were reviewed retrospectively.

Results

Nine children (six boys) aged 3–13 years sustained pancreatic injuries: one grade I (minor contusion), two grade II (major contusion without duct injury or tissue loss), five grade III (distal transection and duct injury) and one grade IV (proximal transection). Grade I and II injuries were successfully managed without surgery. The five children with grade III injuries were initially treated without operation, but each developed a large symptomatic pseudocyst that failed to resolve with percutaneous drainage. Four underwent a spleen-sparing distal pancreatectomy and one boy with a transected pancreatic neck was treated by Roux-en-Y jejunostomy drainage. A 6-year-old boy who sustained severe pancreatobiliary trauma (grade IV) was treated by Roux-en-Y drainage. All children made a full recovery.

Conclusion

The management of pancreatic injuries in children should be individualized depending on the site of injury, timing of referral, presence of associated injuries and institutional expertise.
Quality of life after curative or palliative surgical treatment of pancreatic and periampullary carcinoma
Authors: Nieveen van Dijkum E J M , Kuhlmann K F D , Terwee C B , Obertop H , de Haes J C J M , Gouma D J
Published: January 2005

Background

Quality of life (QOL) is an important outcome measure after treatment of pancreatic and periampullary carcinoma. The aim of this prospective longitudinal study was to analyse QOL after surgery for resectable pancreatic or periampullary carcinoma.

Methods

Patients with potentially resectable tumours underwent pancreaticoduodenectomy (n = 72) or a double-bypass procedure (n = 42). They were asked to complete a questionnaire before laparotomy and at 2 weeks, 6 weeks, and 3, 6, 9 and 12 months after surgery. Fifty-nine patients completed a shortened questionnaire on a weekly basis.

Results

There was a temporary decrease in physical and gastrointestinal functioning after pancreaticoduodenectomy. A similar decrease in QOL was observed after double bypass, as well as decreases in mental functioning and overall QOL. Almost all QOL scores returned to preoperative values by about 3 months after surgery, although only briefly so in patients who had a double-bypass procedure. There were no differences between groups in the terminal stages of disease. A rapid decrease on all QOL scales was observed in the last 8 weeks before death.

Conclusion

Surgery for pancreatic and periampullary carcinoma was not associated with irreversible impairment or protracted recovery of QOL. The relatively long plateau phase after recovery supports the argument for surgical treatment, including surgical palliation in selected patients.