bluuebunny/crossref_metadata_2025 huggingface dataset:
Validity and completeness of the General Practice Research Database for studies of inflammatory bowel disease
Authors: Lewis James D. , Brensinger Colleen , Bilker Warren B. , Strom Brian L.
Published: August 2002

Purpose

The objective of this study was to evaluate the validity and completeness of the General Practice Research Database (GPRD) as a tool for research into inflammatory bowel disease epidemiology.

Methods

Patients diagnosed with inflammatory bowel disease were identified from GPRD. Mailed surveys were sent to the general practitioner caring for a stratified random sample of 170 of these patients and collected information on the diagnosis of inflammatory bowel disease and the most recent surgery and hospitalization.

Results

Usable surveys were returned for 157 patients (92%). The inflammatory bowel disease diagnosis was highly probable or probable in 144 (92%, 95% CI 86 to 96%). Among the 53 patients with a potentially incident inflammatory bowel disease diagnosis, 33 (62%) had the first recorded diagnosis in GPRD within 30 days of the date reported in the survey (median difference −8 days; interquartile range 0 to −81days). Of 12 surgeries and 25 hospitalizations reported in the survey, 11 (92%) and 19 (76%) were identified in GPRD, respectively.

Conclusions

The diagnosis of inflammatory bowel disease in GPRD appears reliable for most patients. Important medical events such as hospitalizations and surgery are recorded at a high rate, although algorithms to identify these events are complex. Copyright © 2002 John Wiley & Sons, Ltd.
Triphenylphosphine oxide‐based bismaleimide and poly(bismaleimide): Synthesis, characterization, and properties
Authors: Liu Ying Ling , Liu Yuan Ling , Jeng Ru Jong , Chiu Yie‐Shun
Published: August 2002

A novel phosphorus‐containing bismaleimide, 3,3′‐bis(maleimidophenyl)phenylphosphine oxide (BMPPPO), was synthesized from triphenylphosphine oxide. This bismaleimide exhibited good solubility in common organic solvents, such as methylethylketone, methylisobutylketone, dichloromethane, chloroform, tetrahydrofuran, acetone, methanol, ethanol, and hot toluene. A low melting point (Tm = 148 °C), a relatively low polymerization temperature (Tp = 214 °C), and a wide processing window (Tp − Tm = 66 °C) were also obtained for BMPPPO. This implies better processing capability. In contrast to most known phosphorus‐containing polymers, the incorporation of BMPPPO into poly(bismaleimide) enhanced the polymer glass‐transition temperature. Thermal stability at temperatures over 550 °C and char yields in the high‐temperature region over 700 °C were also improved. As a result, the flame‐retardant properties of the poly(bismaleimide)s were improved. © 2001 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 39: 1716–1725, 2001
Copolymerization of propylene with various higher α‐olefins using silica‐supported rac‐Me2Si(Ind)2ZrCl2
Authors: Xu Jun‐Ting , Zhu Yin‐Bang , Fan Zhi‐Qiang , Feng Lin‐Xian
Published: August 2002

The copolymerization of propylene with 1‐hexene, 1‐octene, 1‐decene, and 1‐dodecene was carried out with silica‐supported rac‐Me2Si(Ind)2ZrCl2 as a catalyst. The copolymerization activities of the homogeneous and supported catalysts and the microstructures of the resulting copolymers were compared. The activity of the supported catalyst was only one‐half to one‐eighth of that of the homogeneous catalyst, depending on the comonomer type. The supported catalyst copolymerized more comonomer into the polymer chain than the homogeneous catalyst at the same monomer feed ratio. Data of reactivity ratios showed that the depression in the activity of propylene instead of an enhancement in the activity of olefinic comonomer was responsible for this phenomenon. We also found that copolymerization with α‐olefins and supporting the metallocene on a carrier improved the stereoregularity and regioregularity of the copolymers. The melting temperature of all the copolymers decreased linearly with growing comonomer content, regardless of the comonomer type and catalyst system. Low mobility of the propagation chain in the supported catalyst was suggested as the reason for the different polymerization behaviors of the supported catalyst with the homogeneous system. © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 39: 3294–3303, 2001
Rheological properties and foam processability for blends of linear and crosslinked polyethylenes
Authors: Yamaguchi Masayuki , Suzuki Ken‐Ichi
Published: August 2002

The effect of blending crosslinked linear low‐density polyethylene (cLLDPE) on the rheological properties and foam processability of linear low‐density polyethylene was studied. A small addition of cLLDPE, which had a low density of crosslink points, enhanced strain‐hardening behavior in the elongational viscosity to a great degree, although it had little effect on the steady‐state shear viscosity. The enhanced strain hardening reduced heterogeneous deformation during foaming. As a result, a foam with a uniform cell size distribution was obtained. © 2001 John Wiley & Sons, Inc. J Polym Sci Part B: Polym Phys 39: 2159–2167, 2001
Life after cancer: adaptation issues faced by Chinese gynaecological cancer survivors in Hong Kong
Authors: Molassiotis Alexander , Chan Carmen W.H. , Yam Bernard M.C. , Chan Eunice S.J. , Lam Charlotte S.W.
Published: August 2002

An explorative study using qualitative data collection methods was used to look at the adaptation issues faced by Chinese survivors of gynaecological cancers. Eighteen women who were free from illness and between 2 and 16 years post‐diagnosis participated. Content analysis of the data revealed that cancer and its treatment led to a positive revival of these women as they re‐evaluated their life, started treasuring family relationships, improved their mood and became more sensitive to other people's needs. However, they also described problems with marital relationships, concerns about the future of their children, sexuality and femininity, loss of fertility and discomfort due to pain and weakness. A third of the sample reported that their husbands had extramarital affairs. Despite this, women, especially those who had good communication with their partners, commented that they maintained a loving relationship. Cultural beliefs and misconceptions about sexual functioning were also depicted as affecting adaptation to illness. Long‐term psychosocial care may help these women to adapt better to the demands of the illness, especially sexual and psychosexual rehabilitation, as sexual problems were reported by all women in the study. Copyright © 2002 John Wiley & Sons, Ltd.
Individual quality of life in patients with leukaemia and lymphoma
Authors: Montgomery Charles , Pocock Marilyn , Titley Kirsten , Lloyd Keith
Published: August 2002

With increasingly sophisticated chemotherapy regimes being prescribed the quality of life of cancer patients has become a key outcome measure. Little has been reported concerning the experience of patients with haematological malignancy receiving chemotherapy. The objective of this study was to evaluate the clinical usefulness of a novel quality of life measure—the Schedule for the Evaluation of Individual Quality of Life—Direct Weighting (SEIQoL‐DW) in a sample of patients with either leukaemia or lymphoma. Fifty‐one patients from the haematology clinic and in‐patient unit at The Royal Devon and Exeter Hospital completed the SEIQoL‐DW; in addition, each patient completed the Hospital Anxiety and Depression Scale (HADS) and a ten item questionnaire covering aspects of their treatment and satisfaction with information provided. The practical application of the SEIQoL‐DW is described and two patients quality of life profiles are illustrated for comparison. The relationship between quality of life, satisfaction with information provided and psychological distress as measured by the HADS is discussed. Copyright © 2002 John Wiley & Sons, Ltd.
Early pulmonary infection, inflammation, and clinical outcomes in infants with cystic fibrosis*
Authors: Rosenfeld Margaret , Gibson Ronald L. , McNamara Sharon , Emerson Julia , Burns Jane L. , Castile Robert , Hiatt Peter , McCoy Karen , Wilson Christopher B. , Inglis Andrew , Smith Arnold , Martin Thomas R. , Ramsey Bonnie W.
Published: August 2002

A thorough understanding of the early natural history of cystic fibrosis (CF) lung disease is critical for the development of effective interventions in the youngest patients. We assessed the evolution of pulmonary infection, inflammation, and clinical course among 40 infants over a 2‐year period through annual bronchoalveolar lavage (BAL) for culture and measurements of pro‐ and anti‐inflammatory cytokines, semiannual infant pulmonary function testing, and quarterly clinical evaluations.

Both the prevalence of CF pathogens and their density in BAL fluid increased with age. Infants had neutrophilic lower airway inflammation and elevated IL‐8 concentrations independent of whether CF pathogens were recovered. Total leukocyte and neutrophil densities and IL‐8 concentrations increased with density of CF pathogens in BAL fluid, whether the isolated organism was P. aeruginosa or another pathogen. IL‐10 concentrations were similar in CF subjects and non‐CF historical controls. Infants generally had suboptimal growth (low weight and height percentiles) and obstructive lung disease (decreased expiratory flows and air trapping). Subjects from whom CF pathogens were isolated at > 105 cfu/mL had the worst air trapping and lowest Brasfield chest X‐ray scores.

Our findings provide a foundation for future studies of early intervention in CF lung disease, including antimicrobial and anti‐inflammatory therapy. Pediatr Pulmonol. 2001; 32:356–366. © 2001 Wiley‐Liss, Inc.
Improving the prediction of protein secondary structure in three and eight classes using recurrent neural networks and profiles
Authors: Pollastri Gianluca , Przybylski Darisz , Rost Burkhard , Baldi Pierre
Published: August 2002

Secondary structure predictions are increasingly becoming the workhorse for several methods aiming at predicting protein structure and function. Here we use ensembles of bidirectional recurrent neural network architectures, PSI‐BLAST‐derived profiles, and a large nonredundant training set to derive two new predictors: (a) the second version of the SSpro program for secondary structure classification into three categories and (b) the first version of the SSpro8 program for secondary structure classification into the eight classes produced by the DSSP program. We describe the results of three different test sets on which SSpro achieved a sustained performance of about 78% correct prediction. We report confusion matrices, compare PSI‐BLAST to BLAST‐derived profiles, and assess the corresponding performance improvements. SSpro and SSpro8 are implemented as web servers, available together with other structural feature predictors at: http://promoter.ics.uci.edu/BRNN‐PRED/. Proteins 2002;47:228–235. © 2002 Wiley‐Liss, Inc.
Simple sequences are rare in the Protein Data Bank
Authors: Huntley Melanie A. , Golding G. Brian
Published: August 2002

A simple sequence is abundant in the proteins that have been sequenced to date. But unusual protein features, such as a simple sequence, are not present in the same high frequency within structural databases. A subset of these simple sequences, a group with a highly repetitive nature has been shown to be abundant in eukaryotes but not in prokaryotes. In this study, an examination of the eukaryotic proteins in the Protein Data Bank (PDB) has revealed a large deficiency of low complexity, highly repetitive protein repeats. Through simulated databases of similar samples of eukaryotic proteins taken from the National Center for Biotechnology Information (NCBI) database, it is shown that the PDB contains a significantly less highly repetitive, simple sequence than artificial databases of similar composition randomly derived from NCBI. When the structural data for those few PDB sequences that did contain a highly repetitive simple sequence is examined in detail, it is found that in most cases the tertiary structure is unknown for the regions consisting of a simple sequence. This lack of a simple sequence both in the PDB database and in the structural information suggests that this type of simple sequence may produce disordered structures that make structural characterization difficult. Proteins 2002;48:134–140. © 2002 Wiley‐Liss, Inc.
Synthesis and molluscicidal structure–activity relationships of some novel 1,2,4‐triazole N‐methyl carbamates
Authors: Radwan Mohamed A , El‐Zemity Saad R
Published: August 2002

A new series of 1,2,4‐triazole derivatives and their corresponding carbamates have been synthesized and screened for their molluscicidal activity against two types of terrestrial snail, Helix aspersa and Theba pisana, by two methods of application, either as contact or as bran baits. Several of the tested compounds exhibited good molluscicidal activity, and T pisana was more sensitive than H aspersa. Substitution at the o‐ and/or p‐positions of the phenyl ring with chlorine or bromine gave higher molluscicidal activity than the unsubstituted compound, with o,p‐dichloro substitution being optimum. In addition, compounds containing two triazole moieties showed higher molluscicidal activity, particularly as stomach poisons, than the contact toxic effect of the corresponding compound with one triazole ring. In general, carbamate derivatives were more active than their corresponding 1,2,4‐triazole derivatives.

© 2001 Society of Chemical Industry
Antioxidant action of Tinospora cordifolia root extract in alloxan diabetic rats
Authors: Stanely Mainzen Prince P. , Menon Venugopal P.
Published: August 2002

Tinospora cordifolia is widely used in Indian Ayurvedic medicine for the treatment of diabetes mellitus. Oral administration of 2.5 g and 5.0 g/kg body weight of the aqueous extract of the roots for 6 weeks resulted in a significant reduction in thiobarbituric acid reactive substances (TBARS) and an increase in reduced glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD) in alloxan diabetic rats. The effect of Tinospora cordifolia root extract (TCREt) was most prominently seen in the case of rats given 5.0 g/kg body weight. The effect of TCREt was more effective than glibenclamide. Thus our study shows that TCREt exhibits antioxidant action in alloxan diabetes. Copyright © 2001 John Wiley & Sons, Ltd.
Blood chemistry of rats pretreated with Mucuna Pruriens seed aqueous extract MP101UJ after Echis carinatus venom challenge
Authors: Aguiyi J. C. , Guerranti R. , Pagani R. , Marinello E.
Published: August 2002

The effect of a lethal Echis carinatus venom on serum enzyme levels and blood plasma coagulation parameters in rats pretreated with Mucuna pruriens seed aqueous extract MP101UJ (21 mg/kg body wt) 24 h and 3 wk before i.p venom injection (0.50 mg/kg rat) and rats injected with venom alone (0.50 mg/kg body wt) was investigated. The enzyme levels and coagulation parameter levels were measured 4 h after venom administration. The results showed that the increased enzymes lactate dehydrogenase (LDH), glutamic pyruvic transaminase (SGPT), creatinine kinase (CK) and changed coagulation parameters D‐Dimer and Quick levels due to the venom effect were inhibited by M. pruriens seed aqueous extract MP101UJ in pretreated rats. Rats pretreated with a single dose (21 mg/kg and multiple doses 21 mg/kg rat) of extract MP101UJ maintained the normal enzyme levels and showed an anticoagulant effect as evidenced by the high PTT level which was also observed in venom treated animals. D‐Dimer and Quick values were normal. However, the extract MP101UJ appeared to significantly inhibit the lethal venom induced myotoxic, cytotoxic and coagulation activities in experimental animals. Copyright © 2001 John Wiley & Sons, Ltd.
Electron propagator calculations with Kohn–Sham reference states
Authors: Shigeta Y. , Ferreira A. M. , Zakrzewski V. G. , Ortiz J. V.
Published: August 2002

Kohn–Sham orbitals are employed in a generalization of the 2p–h Tamm–Dancoff approximation derived for a determinantal reference state. Neglect of certain terms in the superoperator couplings between triple field operator products recovers the so‐called GW approximation, which has been extensively applied in solid state physics. Further simplifications are examined as well. The performance of these approximations with several exchange–correlation potentials is assessed by comparing calculated ionization energies with their counterparts obtained with electron propagator methods based on Hartree–Fock reference states. © 2001 John Wiley & Sons, Inc. Int J Quantum Chem, 2001
Increased throughput in quantitative bioanalysis using parallel‐column liquid chromatography with mass spectrometric detection
Authors: Jemal Mohammed , Huang Mike , Mao Yan , Whigan Daisy , Powell Mark L.
Published: August 2002

The feasibility of quantitative bioanalysis by parallel‐column liquid chromatography in conjunction with a conventional single‐source electrospray mass spectrometer has been investigated using plasma samples containing a drug and its three metabolites. Within a single chromatographic run time, sample injections were made alternately onto each of two analytical columns in parallel at specified intervals, with a mass spectrometer data file opened at every injection. Thus, the mass spectrometer collected data from two sample injections into separate data files within a single chromatographic run time. Therefore, without sacrificing the chromatographic separation or the selected reaction monitoring (SRM) dwell time, the sample throughput was increased by a factor of two. Comparing the method validation results obtained using the two‐column system with those obtained using the corresponding conventional single‐column approach, the methods on the two systems were found to be equivalent in terms of accuracy and precision. The parallel‐column system is simple and can be implemented using existing laboratory equipment with no additional capital outlays. A parallel‐column system configured in this manner can be used not only for the within‐a‐run analysis of two samples containing two different sets of chemical entities, but also for the within‐a‐run analysis of two samples containing the same set of chemical entities. Copyright © 2001 John Wiley & Sons, Ltd.
Ecological effects of flow regulation on macroinvertebrate and periphytic diatom assemblages in the Hawkesbury–Nepean River, Australia
Authors: Growns Ivor O. , Growns Jane E.
Published: August 2002

The effects of flow regulation on macroinvertebrates and periphytic diatoms were examined in the Hawkesbury–Nepean River system in Australia. Regulated sites below eight dams or weirs were compared with unregulated sites above the impoundments and sites on two nearby unregulated streams. The management of the water supply during the study created two types of flow regulation, sites with water supply releases and sites with comparatively small or no releases. The macroinvertebrate communities in three habitats and periphytic diatoms below the storages and weirs differed from the biota at unregulated sites above the weirs and on unregulated systems. The number of macroinvertebrate taxa in riffle and pool‐rock assemblages was significantly lower at regulated sites when compared with unregulated sites and the number of stream edge macroinvertebrate and diatom taxa was unaffected by regulation. Riffle and pool‐rock macroinvertebrate assemblages differed between the two types of regulation. However, periphytic diatom and edge habitat macroinvertebrate assemblages did not differ between the two types of flow regulation. Examination of environmental variables associated with the change in the biota suggested that the principal effect of the management of the water supply system in the Hawkesbury–Nepean River was changed hydrology rather than altered water quality. Copyright © 2001 John Wiley & Sons, Ltd.
Using pedagogical inquiries as a basis for learning to teach: Prospective teachers' reflections upon positive science learning experiences
Authors: Van Zee Emily H. , Roberts Deborah
Published: August 2002

The primary purpose of this study was to document and interpret ways in which the first author engaged prospective teachers in pedagogical inquiries and then assisted them in using their findings as a basis for learning to teach in her courses on methods of teaching science in elementary schools. The focus here is upon inquiries about factors that foster science learning. A second purpose was to trace some of the effects of such a pedagogical approach in the development of expertise in teaching, researching, and mentoring. A third purpose was to contribute to the development of interpretative methodology, an example of a collaborative inquiry. Data included drawings made by prospective teachers on the first day of class in which they depicted memories of positive experiences in learning science. They also wrote captions for their drawings, identified factors that fostered their learning in these instances, and constructed a joint list of factors across these individual experiences. Throughout the semester, the prospective teachers also wrote journals describing science learning they observed and analyzing factors that fostered learning in those instances. Then they analyzed their own journals for common themes in order to develop personal frameworks for science teaching and learning. Data also included audio‐taped interviews and written reflections by a graduate of the course about ways the course has influenced her evolving teaching and mentoring practices. The results suggest that these prospective elementary school teachers had entered a course on methods of teaching science with prior knowledge about science learning and teaching that could serve as a basis for learning to use approaches to science instruction advocated in the national standards. The reflective methods utilized in the course enabled at least one of these prospective teachers to articulate her philosophy of teaching in ways that helped her instantiate such practices as a beginning teacher. © 2001 John Wiley & Sons, Inc.Sci Ed 85:733–757, 2001.
Trade and environment: evidence from China's manufacturing sector
Authors: Chai Joseph C. H.
Published: August 2002

This paper focusing on the Chinese manufacturing sector assesses the environmental impact of trade liberalization in China. The results show that China's experience with the trade liberalization–environment nexus is consistent with international evidence. On one hand, trade liberalization has had various positive effects on the environment. Firstly, it promoted specialization in areas of comparative advantage, which, in general, included industries that contributed less to environmental degradation. Secondly, it allowed China to access and adopt the best international practices in pollution abatement technology. Thirdly, it enabled China to transfer environmental costs to other countries by importing intermediate products whose production contributed to environmental degradation. On the other hand, these positive effects were overwhelmed by a negative scale effect, which was the result of a huge increase in the demand for Chinese exports. The paper concludes that if China is to prevent pollution from reaching a critical threshold, environmental regulations need to be tightened. Copyright © 2002 John Wiley & Sons, Ltd. and ERP Environment.
Evaluation of irrigation projects and water resource management: a methodological proposal
Authors: Rodríguez Manuel Martín , Sáez Fernández Francisco Javier , Aragón Correa Juan Alberto , Ferrer Elías Melchor , Ferrero Noelina Rodríguez
Published: August 2002

Traditionally, water policy in Spain, and particularly as regards irrigation, has paid little attention to the analysis of efficiency in management aspects. This reality is in juxtaposition with the growing difficulties observed in satisfying water demand and with social demands in terms of the efficient use of public money.

In this paper a methodology is proposed, which could be particularly useful for the economic‐financial evaluation of public irrigation works. Both public and private cash flows generated by investments are considered and updated using the net current value criterion (NCV). After formulation of the methodological proposal, a practical application of it is made using the irrigatable areas of Viar, Cacín and Vegas Bajas, located in the river Guadalquivir basin.

The method could be highly useful to aid decision‐making in public and private investments in terms of water resource management, and to estimate productivity and elasticity in the demand for water in farming. Copyright © 2002 John Wiley & Sons, Ltd. and ERP Environment.
Bayesian random effects meta‐analysis of trials with binary outcomes: methods for the absolute risk difference and relative risk scales
Authors: Warn D. E. , Thompson S. G. , Spiegelhalter D. J.
Published: August 2002

When conducting a meta‐analysis of clinical trials with binary outcomes, a normal approximation for the summary treatment effect measure in each trial is inappropriate in the common situation where some of the trials in the meta‐analysis are small, or the observed risks are close to 0 or 1. This problem can be avoided by making direct use of the binomial distribution within trials. A fully Bayesian method has already been developed for random effects meta‐analysis on the log‐odds scale using the BUGS implementation of Gibbs sampling. In this paper we demonstrate how this method can be extended to perform analyses on both the absolute and relative risk scales. Within each approach we exemplify how trial‐level covariates, including underlying risk, can be considered. Data from 46 trials of the effect of single‐dose ibuprofen on post‐operative pain are analysed and the results contrasted with those derived from classical and Bayesian summary statistic methods. The clinical interpretation of the odds ratio scale is not straightforward. The advantages and flexibility of a fully Bayesian approach to meta‐analysis of binary outcome data, considered on an absolute risk or relative risk scale, are now available. Copyright © 2002 John Wiley & Sons, Ltd.
Partial imputation approach to analysis of repeated measurements with dependent drop‐outs
Authors: Wei Lynn , Shih Weichung J.
Published: August 2002

In clinical trials repeated measurements of a response variable are usually taken at prespecified time‐points to compare the treatment effects. However, the comparison of treatment effects is often complicated by missing data caused by the withdrawal of some patients before the end of the study (that is, drop‐outs). When the drop‐out process depends on the response variable of interest, ignoring missing data may lead to biased comparison of the treatment effect. In this paper, conditions for ignoring the dependent missingness are investigated and a new approach using the usual testing procedure based on data with partial carrying‐forward imputation is proposed. The proposed approach is conceptually and practically simple, and is motivated by making incremental improvement on the familiar ‘all available data’ (AAD) approach and the ‘last value carrying forward’ (LVCF) approach, which are commonly used in data analysis with drop‐outs by practitioners. It is also compared favourably to the mixed‐effect model approach with dependent drop‐outs. Simulations and real data are used to evaluate and illustrate statistical properties of the proposed approach. The principle of the proposed approach can also be extended to using other imputation methods such as the multiple imputation. Copyright © 2001 John Wiley & Sons, Ltd.
Detection of occult metastasis in patients with breast cancer
Authors: Hawes Debra , Neville A. Munro , Cote Richard J.
Published: August 2002

The most important factor affecting the outcome of patients with invasive cancer is whether the tumor has spread, either regionally (to regional lymph nodes) or systemically. However, a proportion of patients with no evidence of systemic dissemination will develop recurrent disease after primary “curative” therapy. Clearly, these patients had occult systemic spread of disease that was undetectable by routinely employed methods (careful pathological, clinical, biochemical, and radiological evaluation). In addition, the success of adjuvant therapy is assumed to stem from its ability to eradicate occult metastases before they become clinically evident [1]. Therefore, methods for the detection of occult metastases in patients with the earliest stage of cancer, i.e., prior to detection of metastases by any other clinical or pathological analysis, have received a great deal of attention. Semin. Surg. Oncol. 20:312–318, 2001. © 2001 Wiley‐Liss, Inc.
Distinct gene expression signatures in the striata of wild‐type and heterozygous c‐fos knockout mice following methamphetamine administration: Evidence from cDNA array analyses
Authors: Cadet Jean Lud , McCoy Michael T. , Ladenheim Bruce
Published: August 2002

Methamphetamine (METH) is a drug of abuse which can cause apoptosis and degeneration of monoaminergic terminals in the mammalian brain. c‐fos appears to play a protective role against METH‐induced damage because METH toxicity is exacerbated in c‐fos heterozygous knockout mice. In the present study, we used the comprehensive technique of cDNA array to test the idea that heterozygous c‐fos knockout mice might show differential METH‐induced molecular responses in comparison to wild‐type (WT) animals. Of 1,176 genes examined, the expression of 195 genes in either of the two groups of mice was affected by at least 2‐fold at 2 or 12 h after METH treatment. More genes were either up‐ or downregulated in the WT mice. Moreover, there were substantial differences in the pattern of responses between the two genotypes, with more genes involved in DNA repair and protective processes being upregulated in WT mice after METH administration. These results support the idea that the c‐fos knockout genotype may render the animals unable to trigger multicomponent responses in order to protect against the multifaceted toxic effects of this illicit neurotoxin. Synapse 44:211–226, 2002. © 2002 Wiley‐Liss, Inc.
Inhibition of cytochrome P450 2E1 induces an increase in extracellular dopamine in rat substantia nigra: A new metabolic pathway?
Authors: Nissbrandt Hans , Bergquist Filip , Jonason Jan , Engberg Göran
Published: August 2002

We presented data previously on dopamine (DA) synthesis and catabolism in the rat substantia nigra (SN) suggesting that a substantial part of the synthesized DA in this brain part is metabolized by unknown nonclassical metabolic pathways. On the basis of that a relatively high density of cytochrome P450 2E1 (CYP 2E1) has been detected in rat SN the aim of the present study was to investigate the possibility that this enzyme is involved in the metabolism of DA. Systemic administration of either phenylethyl isothiocyanate (100 mg/kg ip), diethyldithiocarbamate (500 mg/kg, ip) or diallyl sulfide (200 mg/kg, sc or ip), three different inhibitors of cytochrome P450 2E1, induced an increase of the extracellular DA concentration in the SN, measured with microdialysis in awake rats, by 130%, 90%, and 35%, respectively. A tendency to increased concentrations of the classical DA metabolites in the dialysate from the SN was also observed in some experiments. In the striatum, no profound effects were induced by the drugs on the concentrations of DA or its metabolites. The results show that CYP 2E1 activity affects dopaminergic neurotransmission in the SN, possibly by participating in DA metabolism. Other mechanisms, such as the influence on the DA transporter or the release process cannot, however, be ruled out. Synapse 40:294–301, 2001. © 2001 Wiley‐Liss, Inc.
Cholinergic synaptic potentials in the supragranular layers of auditory cortex
Authors: Bandrowski A.E. , Moore S.L. , Ashe J.H.
Published: August 2002

Receptive‐field plasticity within the auditory neocortex is associated with learning, memory, and acetylcholine (ACh). However, the interplay of elements involved in changing receptive‐fields remains unclear. Herein, we describe a depolarizing and a hyperpolarizing potential elicited by repetitive stimulation (20–100 Hz, 0.5–2 sec) and dependent on ACh, which may be involved in modifying receptive‐fields. These potentials were recorded, using whole cell techniques, in layer II/III pyramidal cells in the rat auditory cortex in vitro. Stimulation at low stimulus intensities can give rise to a hyperpolarizing response and stimulation at higher stimulus intensities can elicit a depolarizing response. The depolarizing response had a reversal potential of −35 mV, and was reduced by the combination of AMPA/kainate and NMDA glutamate receptor antagonists (AMPA/kainate: CNQX, DNQX, and GYKI 52466; NMDA: APV, MK‐801) and by the muscarinic ACh receptor antagonist atropine. The hyperpolarizing response had a reversal potential of −73 mV and could be reduced by atropine, GABAA receptor antagonists (bicuculline and a Cl− channel blocker picrotoxin), and to a small extent a GABAB receptor antagonist (saclofen). This suggests that the hyperpolarizing response is likely to be mediated by ACh acting on GABAergic interneurons. Extracellular recordings, also made from layer II/III of cortical slices, yielded a negative‐going potential which was reduced by ionotropic glutamate receptor antagonists (same as above) and by the ACh receptor antagonists atropine and scopolamine, suggesting that this potential was the extracellular representation of the depolarizing response. Synapse 41:118–130, 2001. © 2001 Wiley‐Liss, Inc.
Total regional and global number of synapses in the human brain neocortex
Authors: Tang Yong , Nyengaard Jens R. , De Groot Didima M.G. , Gundersen Hans Jørgen G.
Published: August 2002

An estimator of the total number of synapses in neocortex of human autopsy brains based on unbiased stereological principles is described. Each randomly chosen cerebral hemisphere was stratified into the four major neocortical regions. Uniform sampling with a varying sampling fraction in each region of neocortex was performed. The total volume of each neocortical region was estimated using point counting according to Cavalieri's principle. The ethanolic phosphotungstic acid staining technique was modified for synapses in human autopsy brains. The numerical density of synapses in each neocortical region studied was estimated using the disector at the electron microscopical level. The total number of neocortical synapses in each region was estimated as the product of the total volume of neocortex and the numerical density of synapses. The influence of the postmortem fixation delay on the number of synapses was investigated in five large mammals (one dog, one cow, and three pigs), the brains of which were kept under conditions similar to those under which human corpses are normally kept. The apparent decrease of 3.9% in the numerical density of synapses in the large mammals following a 2‐day fixation delay was not significant. The average total number of synapses in the neocortex of five young male brains was 164 × 1012 (CV = 0.17). An analysis of the precision of the estimate of the total number of synapses in neocortex indicates that blocks represent both the major source of variation and the largest workload. Using eight blocks per brain the imprecision of the estimate is, however, only 66% of the total variance. Synapse 41:258–273, 2001. © 2001 Wiley‐Liss, Inc.
Postmarketing surveillance for human teratogenicity: A model approach
Authors: Chambers Christina D. , Braddock Stephen R. , Briggs Gerald G. , Einarson Adrienne , Johnson Yvette R. , Miller Richard K. , Polifka Janine E. , Robinson Luther K. , Stepanuk Kathleen , Lyons Jones Kenneth
Published: August 2002

Background

Most congenital defects associated with prenatal exposures are notable for a pattern of major and minor malformations, rather than for a single major malformation. Thus, traditional epidemiological methods are not universally effective in identifying new teratogens. The purpose of this report is to outline a complementary approach that can be used in addition to other more established methods to provide the most comprehensive evaluation of prenatal exposures with respect to teratogenicity.

Methods

We describe a multicenter prospective cohort study design involving dysmorphological assessment of liveborn infants. This design uses the Organization of Teratology Information Services, a North American network of information providers who also collaborate for research purposes. Procedures for subject selection, methods for data collection, standard criteria for outcome classification, and the approach to analysis are detailed.

Results

The focused cohort study design allows for evaluation of a spectrum of adverse pregnancy outcomes ranging from spontaneous abortion to functional deficit. While sample sizes are typically inadequate to identify increased risks for single major malformations, the use of dysmorphological examinations to classify structural anomalies provides the unique advantage of screening for a pattern of malformation among exposed infants.

Conclusions

As the known human teratogens are generally associated with patterns of structural defects, it is only when studies of this type are used in combination with more traditional methods that we can achieve an acceptable level of confidence regarding the risk or safety of specific exposures during pregnancy. Teratology 64:252–261, 2001. © 2001 Wiley‐Liss, Inc.
Export promotion: A framework for finding opportunity in change
Authors: Czinkota Michael R.
Published: August 2002

Governments view exports as “special” for their macroeconomic impact. As a result, many governments
have developed programs to assist exporters. In order to function efficiently and to be permissible under the
anti‐subsidy rules of the World Trade Organization (WTO), it is proposed that export promotion
programs become the venture capital of international trade by being innovative and iconoclastic. Particular
attention is recommended for captive trade among affiliates, the generation of unsolicited orders, the rise of new
technology, and the sharing of resources among internationalizing firms. © 2002 Wiley Periodicals, Inc.
Total Thyroidectomy for Management of Thyroid Disease
Authors: Gough Ian R. , Wilkinson David
Published: August 2002

Total thyroidectomy is a logical treatment for many patients with thyroid disease, including patients in whom the pathologic process requiring surgery involves both lobes of the thyroid or the risk of recurrence is a significant consideration, as in benign multinodular goiter, Graves' disease, and cancer. In earlier times the risks of extensive surgery and problems of adequate hormone replacement deterred surgeons from performing total thyroidectomy. However, as we enter the twenty‐first century we are confident that the technical aspects of safe total thyroidectomy are established and that thyroid hormone replacement and monitoring are readily available and accurate. In the future total thyroidectomy is likely to be performed increasingly commonly for both benign and malignant disease.
Complications of Laparoscopic Adrenalectomy: Results of 169 Consecutive Procedures
Authors: Henry Jean‐François , Defechereux Thierry , Raffaelli Marco , Lubrano Denis , Gramatica Luis
Published: August 2002

Laparoscopic adrenalectomy (LA) has become the gold standard for adrenalectomy. Review of the literature indicates that the rate of intra‐ and postoperative complications is not negligible. The aim of this study was to evaluate the complications observed in a series of 169 consecutive LAs performed at a same center for a variety of endocrine disorders. Between June 1994 and December 1998 a series of 169 LAs were performed in 159 patients: 149 unilateral LAs and 10 bilateral LAs. There were 98 women and 61 men with a mean age of 49.7 years (range 22–76 years). There were patients with 61 Conn syndrome, 41 with Cushing syndrome, 1 androgen‐producing tumor, 29 pheochromocytomas, and 37 nonfunctioning tumors. Mean tumor size was 32 mm (range 7–110 mm). LA was performed by a transperitoneal flank approach in the lateral decubitus position. Mean operating time was 129 minutes (range 48–300 minutes) for unilateral LA and 228 minutes (range 175–275 minutes) for bilateral LA. There was no mortality. Twelve patients had a significant complication (7.5%): three peritoneal hematomas requiring (in two cases) laparotomy and (in one case) transfusion; one parietal hematoma; three intraoperative bleeding episodes without need for transfusion; one partial infarction of the spleen; one pneumothorax; one capsular effraction of the tumor; and two deep venous thromboses. Eight tumors were malignant at final histology (4.7%), of which four were completely removed laparoscopically. Conversion to open surgery was required in eight cases (5%): for malignancy in four cases, difficulty of dissection in three cases, and pneumothorax in one case. With a mean follow‐up of 26.58 months (range 6–60 months) all patients are disease‐free. We conclude that LA is a safe procedure. With increasing experience the morbidity becomes minor. To avoid complications LA should be converted to open surgery if local invasion is suspected or if there is difficulty with the dissection.
Persistent Hyperparathyroidism Requiring Surgical Treatment after Kidney Transplantation
Authors: Kinnaert Paul , Nagy Nathalie , Decoster‐Gervy Christine , De Pauw Luc , Salmon Isabelle , Vereerstraeten Pierre
Published: August 2002

There are not many publications describing long‐term follow‐up of persistent hyperparathyroidism requiring surgical treatment after kidney transplantation (PHSKT). In some patients adenomas, rather than multiglandular disease, have been incriminated as the cause of PHSKT. We reviewed the charts of 45 patients followed for 12 to 146 months (median 45 months) after parathyroidectomy for PHSKT. We compared them with (1) those of 951 patients receiving a kidney graft during the same period but not submitted to parathyroidectomy or (2) 90 matched controls selected from this cohort to determine the characteristics of PHSKT patients. The duration of pretransplant dialysis was significantly longer in PHSKT patients than in controls (5.78 ± 0.41 vs. 3.41 ± 0.24 years; p < 0.0001). A total of 166 glands were removed or biopsied. Except for one questionable case, no true adenoma was observed even when only one gland was enlarged. The outcome of surgery was not influenced by the technique (subtotal parathyroidectomy versus total parathyroidectomy and autografting) but depended on the amount of resected parathyroid tissue: no failures and 4 cases of hypoparathyroidism in 34 cases with no missing gland at cervical exploration; 3 failures and no permanent hypoparathyroidism in 11 cases with one or two missing glands. Excision of the enlarged glands only was sufficient to cure the patient. No recurrence was observed. Our results suggest that single gland enlargement in PHSKT results in most cases from different rates of involution of the parathyroids after successful kidney transplantation. When fewer than four glands are discovered, resection of all visible glands with or without grafting corrects hypercalcemia in more than 70% of the cases.
Lower Limb Revascularization and Free Flap Transfer for Major Ischemic Tissue Loss
Authors: Tukiainen Erkki , Biancari Fausto , Lepäntalo Mauri
Published: August 2002

The objective of this study was to assess the value of lower limb revascularization and free flap transfer (LLR‐FFT) in the management of critical leg ischemia and major tissue loss. A total of 29 consecutive patients with critically ischemic leg and major tissue loss underwent 24 simultaneous and 6 staged LLR‐FFT procedures. The main outcome measures were bypass graft patency, free flap viability, leg salvage, patients alive with salvaged leg, and survival. At the 2‐year follow‐up, the bypass graft patency rate was 85%, secondary free flap viability rate was 82%, and 82% of patients achieved leg salvage and were ambulant. If the success was defined as patients being alive with a salvaged leg, the corresponding rate was 80%. Three patients achieved long‐term primary patency and leg salvage despite free flap failure, which occurred during the 30‐day postoperative period. Lower extremity revascularization plus free flap coverage of large ischemic lesions is valuable in achieving long‐term leg salvage. Because revascularization and conventional management of major tissue loss alone can be effective in the management of a small number of cases, staged LLR‐FFT is indicated, when appropriate, for better selection of patients undergoing such an aggressive and demanding treatment.
Targets for Molecular Intervention in Multistep Pulmonary Carcinogenesis
Authors: Schrump David S. , Nguyen Dao M.
Published: August 2002

Lung cancers are a leading cause of mortality worldwide, and most of these neoplasms are directly attributable to tobacco abuse. Recent studies have begun to elucidate molecular mechanisms of multistep aerodigestive tract carcinogenesis, revealing novel targets for intervention in lung cancers and their precursor lesions. This review summarizes the molecular biology of lung cancers in relation to the prognosis and treatment of patients with these neoplasms.
Evolution of Surgery for Liver Hydatidosis from 1950 to Today: Analysis of a Personal Experience
Authors: Cirenei Anacleto , Bertoldi Innocenzo
Published: August 2002

Hydatid disease (echinococcosis) remains a complex worldwide problem in rural areas. Medical treatment does not definitively cure hydatid cysts, and surgical management aims to eliminate the parasite, favoring rapid disappearance of the residual cavity, preventing complications and recurrence, and shortening the hospital stay. In this consecutive series, 298 patients with liver hydatidosis were treated surgically by the authors from 1950 to 1987 in various hospitals in Rome, Italy. Surgery comprised conservative methods (marsupialization and partial cystopericystectomy) and radical methods (total pericystectomy and liver resection). Liver resection was used only if unavoidable. Complications were exudate from the residual cystic cavity, cholerrhagia, and nonspecific incisional fistula. In the entire series, morbidity was 8.7% of which 12.6% was seen with conservative methods and 5.5% with radical methods (p < 0.05); mortality was 3.6%, of which 5.9% was seen with conservative methods and 1.8% with radical methods (p= NS). Over the 37 years, as medical science and complementary therapies progressed, the use of conservative operations diminished and radical treatments increased. Long‐term follow‐up showed that hydatid disease relapsed more frequently in patients who underwent conservative or subtotally radical treatment than in those who underwent radical surgery: eight patients (11.2%) versus one (0.9%) (p < 0.01). Hence surgical treatment that removes all of the pericyst and preservation of the nonpathologic liver are important.