bluuebunny/crossref_metadata_2025 huggingface dataset:
Genotyping single nucleotide polymorphisms using intact polymerase chain reaction products by electrospray quadrupole mass spectrometry
Authors: Walters James J. , Muhammad Warees , Fox Karen F. , Fox Alvin , Xie Dawen , Creek Kim E. , Pirisi Lucia
Published: August 2002

Both single nucleotide polymorphisms (SNPs) and mutations are commonly observed in the gene encoding the tumor suppressor protein, p53. SNPs occur at specific locations within genes whereas mutations may be distributed across large regions of genes. When determining nucleotide differences, mass spectrometry is the only method other than Sanger sequencing which offers direct structural information. Electrospray ionization (ESI) quadrupole mass spectrometry (MS) analysis of intact polymerase chain reaction (PCR) products was performed following a simple purification and on‐line heating to limit ion adduction. The PCR products were amplified directly from genomic DNA rather than plasmids, as in our previous work. Two known polymorphisms of the p53 gene were genotyped. A cytosine (C) or guanine (G) transversion, designated C ↔ G (G ↔ C on the opposite strand), were each detected by a 40.0 Da change upon ESI quadrupole MS analysis. Using known PCR products as standards, the genotypes determined for 10 human samples corresponded with restriction fragment length polymorphism (RFLP) analysis. Cytosine/thymine (T) transitions, designated C ↔ T (G ↔ A on the opposite strand), were also genotyped by ESI‐MS. This SNP is discriminated by a 15.0 Da change on one strand (C ↔ T) and a 16.0 Da change on the other (G ↔ A). Appropriate sample preparation and instrumental configuration (including heated sample inlet syringe and MS source), to limit adducts, are both vital for successful ESI quadrupole MS analysis of intact PCR products. Copyright © 2001 John Wiley & Sons, Ltd.
Fragmentation of N‐oxides (deoxygenation) in atmospheric pressure ionization: Investigation of the activation process
Authors: Tong Wei , Chowdhury Swapan K. , Chen Jin‐Chang , Zhong Ruyun , Alton Kevin B. , Patrick James E.
Published: August 2002

The diagnostic fragmentation of N‐oxides resulting from loss of the oxygen atom (MH+ → MH+‐O) in electrospray and atmospheric pressure chemical ionization (APCI) mass spectra was investigated. When the temperature of the heated capillary tube was elevated, the ratio of the intensity of the [MH+ − 16] fragment to the precursor ion (MH+) increased. This ‘deoxygenation’ process was associated with thermal activation and did not result from collisional activation in the desolvation region of the API source. Although the extent of ‘deoxygenation’ is compound‐dependent, it can provide evidence for the presence of an N‐oxide in a sample and can be used to distinguish N‐oxides from hydroxylated metabolites (Ramanathan et al. Anal. Chem. 2000; 72: 1352). To demonstrate the practical application of thermal fragmentation of N‐oxides, liquid chromatography (LC)/APCI‐MS was used to distinguish an N‐oxide drug from its hydroxylated metabolite in an unprocessed rat urine sample, despite the fact that the drug and its metabolite were not fully resolved by HPLC. Copyright © 2001 John Wiley & Sons, Ltd.
Non‐covalent binding of endogenous ligands to recombinant cellular retinol‐binding proteins studied by mass spectrometric techniques
Authors: Elviri L. , Zagnoni I. , Careri M. , Cavazzini D. , Rossi G. L.
Published: August 2002

Recent developments in mass spectrometry have demonstrated the capability of this technique to transfer non‐covalent protein complexes, involving low and high molecular weight ligands, from a condensed state to the gas phase. In this work, electrospray mass spectrometry with a quadrupole analyzer (ES‐MS) and matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOFMS) were used to analyze the non‐covalent association between recombinant rat cellular retinol‐binding protein type‐I (CRBP) with its specific ligand, all‐trans retinol (vitamin A), and with fatty acids. Under denaturing conditions, MALDI‐TOFMS and ES‐MS techniques allowed determination of the molecular weight of apo‐CRBP with good accuracy (<0.01%) and to identify a protein fraction (∼20%) retaining the initial methionine. By adding saturating amounts of vitamin A, ES‐MS studies on the protein in the holo‐form under native conditions allowed detection of retinol bound within the cavity together with water molecules, as expected from its crystal structure. ES mass spectra of CRBP in the native state were also recorded under non‐denaturing conditions, with the aim to study non‐covalent interactions between CRBP and non‐specific ligands such as fatty acids, bound to the protein as a result of expression in various strains of E. coli grown in different media. Since ES mass spectra do not elucidate which species interact with the protein, in order to investigate the ligands possibly retained in the active site of recombinant CRBP, liquid chromatography/ES‐tandem mass spectrometry was used. In particular, this technique was applied to identify and quantify fatty acids bound to CRBP. Quantitative data indicated the presence of a few fatty acids at a total concentration lower than 2% of that of the protein. Similar findings were observed for the homolog rat cellular retinol‐binding protein type‐II, demonstrating the high degree of purity and homogeneity of apo‐CRBP preparations derived from gene expression. Copyright © 2001 John Wiley & Sons, Ltd.
Liquid chromatography/tandem mass spectrometric quantification with metabolite screening as a strategy to enhance the early drug discovery process
Authors: Tiller Philip R. , Romanyshyn Leslie A.
Published: August 2002

Throughput for early discovery drug metabolism studies can be increased with the concomitant acquisition of metabolite screening information and quantitative analysis using ultra‐fast gradient chromatographic methods. Typical ultra‐fast high‐performance liquid chromatography (HPLC) parameters used during early discovery pharmacokinetic (PK) studies, for example, employ full‐linear gradients over 1–2 min at very high flow rates (1.5–2 mL/min) on very short HPLC columns (2 × 20 mm). These conditions increase sample throughput by reducing analytical run time without sacrificing chromatographic integrity and may be used to analyze samples generated from a variety of in vitro and in vivo studies. This approach allows acquisition of more information about a lead candidate while maintaining rapid analytical turn‐around time. Some examples of this approach are discussed in further detail. Copyright © 2002 John Wiley & Sons, Ltd.
Clinical features of variant Creutzfeldt‐Jakob disease
Authors: Henry Colm , Knight Richard
Published: August 2002

Since 1996, over one hundred cases of variant Creutzfeldt‐Jakob disease have appeared, mostly in the United Kingdom. In this review, we summarise the major clinical features of this progressive neurodegenerative condition and compare them with those of sporadic Creutzfeldt‐Jakob disease. We emphasise the young age (median 26 years) at presentation and the dominant psychiatric/behavioural features, particularly depression. Sensory symptoms are present initially in half the cases and florid psychiatric symptoms, such as delusions or hallucinations, are also common. Given these symptoms, many patients present in clinical practice initially to a psychiatrist but are referred to neurologists when neurological signs become apparent. Although the definitive diagnosis remains neuropathological, a confident pre‐mortem diagnosis is now possible when the ‘pulvinar sign’ is seen on magnetic resonance imaging studies. Copyright © 2002 John Wiley & Sons, Ltd.
Rerum cognoscere causas: Part II—Opportunities generated by the agency/structure debate and suggestions for clarifying the social theoretic position of system dynamics
Authors: Lane David C.
Published: August 2002

This is the second half of a two‐part paper dealing with the social theoretic assumptions underlying system dynamics. In the first half it was concluded that analysing system dynamics using traditional, paradigm‐based social theories is highly problematic. An innovative and potentially fruitful resolution is now proposed to these problems. In the first section it is argued that in order to find an appropriate social theoretic home for system dynamics it is necessary to look to a key exchange in contemporary social science: the agency/structure debate. This debate aims to move beyond both the theories based only on the actions of individual human agents, and those theories that emphasise only structural influences. Emerging from this debate are various theories that instead aim to unite the human agent view of the social realm with views that concentrate solely on system structure. It is argued that system dynamics is best viewed as being implicitly grounded in such theories. The main conclusion is therefore that system dynamics can contribute to an important part of social thinking by providing a formal approach for explicating social mechanisms. This conclusion is of general significance for system dynamics. However, the over‐arching aim of the two‐part paper is to increase the understanding of system dynamics in related disciplines. Four suggestions are therefore offered for how the system dynamics method might be extended further into the social sciences. It is argued that, presented in the right way, the formal yet contingent feedback causality thinking of system dynamics should diffuse widely in the social sciences and make a distinctive and important contribution to them.

Felix qui potuit rerum cognoscere causas

‘Happy is he who comes to know the causes of things’

Virgil—Georgics, Book II, line 490. 29 BCE

Copyright © 2001 John Wiley & Sons, Ltd.
Mechanisms for pitting corrosion in alloy N04400 as revealed by imaging XPS, ToF‐SIMS and low‐voltage SEM
Authors: Francis J. T. , McIntyre N. S. , Davidson R. D. , Ramamurthy S. , Brennenstühl A. M. , McBride A. , Roberts A.
Published: August 2002

Imaging XPS has been used to determine the distributional patterns of corrosion products of different chemistry on a nickel–copper alloy surface that has been subjected to pitting corrosion. Separate regions within corrosion pits can be identified with chemical processes that are suggested to be anodic and cathodic in nature. The anodic processes are indicated by a thin layer of cuprous oxide covering the base alloy, suggesting the preferential dissolution of nickel. Areas undergoing a cathodic process are indicated by the deposition of nickel as an oxide or hydroxide. Adjacent regions also were studied by XPS and characterized further by low‐voltage SEM/energy‐dispersive x‐ray imaging and time‐of‐flight SIMS techniques to obtain confirmatory and complementary information. Typically, the anodic and cathodic areas were tens of microns in size. Copyright © 2002 John Wiley & Sons, Ltd.
Interaction of a polycrystalline silver powder with ozone
Authors: Waterhouse G. I. N. , Bowmaker G. A. , Metson J. B.
Published: August 2002

The interaction of a polycrystalline silver powder with ozone (5 mol.% O3 in O2) was investigated over the temperature range 300–923 K. Silver powder samples were reacted with ozone for 30 min at specified temperatures in this range. All experiments were performed at atmospheric pressure. Following treatment, samples were cooled rapidly to room temperature under a nitrogen gas purge and then characterized by scanning electron microscopy, powder x‐ray diffraction, Raman spectroscopy and x‐ray photoelectron spectroscopy. The morphology, structure and chemical composition of the oxide products formed at different reaction temperatures were examined. The silver powder blackened immediately upon contact with the reaction gas mixture at 300 K, due to the formation of silver (I) oxide (Ag2O). After reaction with O3 for 30 min at 300 K, a mixed‐oxide phase comprised of Ag2O and monoclinic silver (I, III) oxide (AgO) was formed. The AgO was formed at the gas/oxide interface via the oxidation of Ag2O. A tetragonal AgO polymorph was formed when the silver powder was reacted with ozone at 473 K. The only product of silver oxidation by O3 at 673 K was Ag2O, which remained stable in the reaction gas to temperatures in excess of 773 K. The silver powder was not oxidized by ozone at 923 K, although the powder did sinter extensively during the treatment. The experimental data presented are in good accord with available thermodynamic data pertaining to the thermal stability of Ag2O and AgO in ozonized oxygen at atmospheric pressure. Copyright © 2002 John Wiley & Sons, Ltd.
Maximally selected measures of evidence of disease clusters
Authors: Burr Tom L.
Published: August 2002

It is now common to read reports such as ‘city A has a childhood cancer rate 30 per cent higher than the national average’. Because the details about how the data was examined can greatly impact the conclusions, the epidemiologist then wants to know more information, such as ‘over what time period’ and ‘how many other cancer types were examined’. For example, city A might have calculated cancer rates for many age groups within different regions of the city over many time intervals, but reported only the highest cancer rate discovered in a particular group. We will refer to such selective reporting as ‘maximally selecting measures of evidence of disease clustering’, or less formally as ‘fishing for statistical significance’. The objective of this paper is to study the behaviour of maximally selected statistics for measuring the extent of clustering in disease outbreaks. The original data is the time and location of each reported case of the disease. In some cases we are only given aggregates of the original data, such as the number of cases during a time period over a given region. We introduce new and review existing methods for correcting for the effect of making maximal selections in disease cluster detection. We consider three main cases with examples. We demonstrate via simulation and analytical approximations that some types of ‘fishing’ are simple to correct for while others are not. Copyright © 2001 John Wiley & Sons, Ltd.
The maintenance implications of the customization of ERP software
Authors: Light Ben
Published: August 2002

Enterprise resource planning (ERP) software is a dominant approach for dealing with legacy information system problems. In order to avoid invalidating maintenance and development support from the ERP vendor, most organizations reengineer their business processes in line with those implicit within the software. Regardless, some customization is typically required. This paper presents two case studies of ERP projects where customizations have been performed. The case analysis suggests that while customizations can give true organizational benefits, careful consideration is required to determine whether a customization is viable given its potential impact upon future maintenance. Copyright © 2001 John Wiley & Sons, Ltd.
Dealing with the complexity of business systems architecting
Authors: Biemans F.P.M. , Lankhorst M.M. , Teeuw W.B. , van de Wetering R.G.
Published: August 2002

Engineers are trained to design systems such as bridges, computers, and aircraft in a well‐structured manner. However, the design of business processes has not yet matured to this level. We argue that the complexity of business processes is the major cause. In this paper, we investigate the causes of this complexity, and provide heuristics to master this complexity. Business process “architecting,” the high‐level, functional design of business processes, is more an art than a science. Consequently, experience is very important. The heuristics we provide are based on an analysis of the reasons why business process architecting is so complex as well as our experience resulting from the Testbed project, a cooperative project of industry and research organizations. We conclude by discussing some basic requirements for modeling concepts and methods. © 2001 John Wiley & Sons, Inc. Syst Eng 4: 118–133, 2001
Interaction‐based design tables for transfer beams supporting in‐plane loaded shear walls
Authors: Kuang J. S. , Li Shubin
Published: August 2002

The analysis and behaviour of transfer beams that support in‐plane loaded shear walls have been receiving added emphasis owing to their importance in connection with the design of tall buildings. In this paper, analysis and structural behaviour of transfer beams supporting in‐plane loaded shear walls are presented, where emphasis is placed on the interaction between the transfer beam and the supported shear wall. The interaction effect is shown to cause significant stress re‐distributions both in the transfer beam and in the shear wall within an interactive zone. Parameters that significantly influence the structural behaviour and force transfer mechanism are also highlighted. Based on finite element analysis, interaction‐based design tables are constructed and presented for the design of the transfer beam–shear wall system, which is represented by an equivalent portal frame. The design tables have been shown to provide practising engineers a very simple and efficient, yet accurate, means of analysis of the internal forces of the transfer beams and the support columns. Copyright © 2001 John Wiley & Sons, Ltd.
Effects of folate supplementation on the risk of spontaneous and induced neural tube defects in Splotch mice
Authors: Gefrides Lisa A. , Bennett Gregory D. , Finnell Richard H.
Published: August 2002

Background

Neural tube defects (NTDs) are among the most common human congenital malformations. Although clinical investigations have reported that periconceptional folic acid supplementation can reduce the occurrence of these defects, its mechanism remains unknown. Therefore, the murine mutant Splotch, which has a high incidence of spontaneous NTDs, along with the inbred strains SWV and LM/Bc, were used to investigate the relationship between folate and NTDs.

Methods

To investigate whether folates could reduce spontaneous NTDs, heterozygous Splotch dams (+/Sp) were treated with either folate or folinic acid throughout neurulation, gestational day (GD) 6.5 to 10.5. On GD 18.5 the dams were sacrificed and the fetuses examined for any neural tube defects. Subsequently, Sp/+ dams were treated with arsenic while receiving either a folate or folinic acid supplementation. Similar experiments were performed in the LM/Bc and SWV strains.

Results

Neither folate nor folinic acid supplements reduced the frequency of spontaneous NTDs in the embryos from Splotch heterozygote crosses. Arsenic increased the frequency of NTDs and embryonic death in the Splotch, LM/Bc and SWV litters and folinic acid failed to ameliorate the teratogenic effect of this metal. A folate supplement given to arsenic‐treated dams proved to be maternally lethal in all three strains.

Conclusions

Splotch embryos were not protected from either spontaneous or arsenic‐induced NTDs by folinic or folic acid supplementation. Furthermore, folinic acid supplements did not reduce the incidence of arsenic‐induced NTDs in either the LM/Bc or SWV litters. Teratology 65:63–69, 2002. © 2002 Wiley‐Liss, Inc.
Effect of prenatal exposure to anticonvulsant drugs on dermal ridge patterns of fingers
Authors: Bokhari Aqiba , Coull Brent A. , Holmes Lewis B.
Published: August 2002

Background

An altered frequency of specific dermal ridge patterns on fingertips, such as an increased number of arches, has been observed in children exposed in utero to anticonvulsants and other teratogens. Asymmetry of the distribution of dermal ridge patterns has been attributed to environmental exposures and genetic factors.

Methods

We evaluated all of the dermal ridge patterns of 66 children who had been exposed to either the anticonvulsant phenytoin alone or phenytoin and phenobarbital. We determined the frequency of each pattern, concordance between the fingers on the left and right hands, sex differences and total ridge counts in the drug‐exposed children and compared them to the findings in 716 unexposed comparison children. The frequency of each pattern was established in comparison to the most common type of pattern (ulnar loop), which showed that there were alterations in the frequency of arches, radial loops and whorls on specific fingers.

Results

Eight (12.1%) of 66 children had three or more arch patterns, with all but one having been exposed to phenytoin and phenobarbital. Only one of these eight children was considered by the masked examiner to have fingernail hypoplasia. There was no evidence of asymmetry in the anticonvulsant‐exposed children. There were minor differences in the distribution of total ridge count.

Conclusions

Subtle differences in several dermal ridge patterns, not just arch patterns, were present in anticonvulsant‐exposed children, primarily in those exposed to polytherapy: phenytoin and phenobarbital. Teratology 66:19–23, 2002. © 2002 Wiley‐Liss, Inc.
Modelling utility‐scale wind power plants. Part 2: Capacity credit
Authors: Milligan Michael R.
Published: August 2002

As the worldwide use of wind turbine generators in utility‐scale applications continues to increase, it will become increasingly important to assess the economic and reliability impact of these intermittent resources. Although the utility industry appears to be moving towards a restructured environment, basic economic and reliability issues will continue to be relevant to companies involved with electricity generation. This article is the second in a two‐part series that addresses modelling approaches and results that were obtained in several case studies and research projects at the National Renewable Energy Laboratory (NREL). This second article focuses on wind plant capacity credit as measured with power system reliability indices. Reliability‐based methods of measuring capacity credit are compared with wind plant capacity factor. The relationship between capacity credit and accurate wind forecasting is also explored. Published in 2000 by John Wiley & Sons, Ltd.
A model for low‐energy thick‐target bremsstrahlung produced in a scanning electron microscope
Authors: Semaan Mars , Quarles C. A.
Published: August 2002

Thick‐target bremsstrahlung measurements were obtained for various atomic numbers and for energies between 10 and 25 keV. A Jeol JSM 6100 scanning electron microscope was used for the electron beam and a Oxford Instruments Link Si(Li) detector for the bremsstrahlung spectrum. The experimental data were compared with a model that computes the thick‐target bremsstrahlung spectrum by integrating the tabulated relativistic partial‐wave doubly differential cross‐section for thin‐target bremsstrahlung over the target taking electron energy loss into account in the continuous slowing down approximation. The model corrects for electron backscattering, x‐ray attenuation in the target and the efficiency of the x‐ray detector. Very good agreement was found between the model and the experimental results. Extension of the model to consider multiple scattering in the target is also discussed. Copyright © 2001 John Wiley & Sons, Ltd.
Human pancreatic glucokinase (GlkB) complements the glucose signalling defect of Saccharomyces cerevisiae hxk2 mutants
Authors: Mayordomo Isabel , Sanz Pascual
Published: August 2002

Human pancreatic glucokinase (GlkB, hexokinase IV) has been expressed in Saccharomyces cerevisiae. The recombinant protein showed similar enzyme kinetics to those described for the original enzyme. When expressed in hxk2 yeast mutants, GlkB complemented both the glucose induction and the glucose repression defects present in the mutant. It was also functional in regulating the activity of the Snf1 kinase complex in response to glucose, participating in the regulation of the Reg1/Glc7 phosphatase complex, as its yeast counterpart. Copyright © 2001 John Wiley & Sons, Ltd.
Historic Landmarks in Clinical Transplantation: Conclusions from the Consensus Conference at the University of California, Los Angeles
Authors: Groth Carl G. , Brent Leslie B. , Calne Roy Y. , Dausset Jean B. , Good Robert A. , Murray Joseph E. , Shumway Norman E. , Schwartz Robert S. , Starzl Thomas E. , Terasaki Paul I. , Thomas E. Donnall , van Rood Jon J.
Published: August 2002

The transplantation of organs, cells, and tissues has burgeoned during the last quarter century, with the development of multiple new specialty fields. However, the basic principles that made this possible were established over a three‐decade period, beginning during World War II and ending in 1974. At the historical consensus conference held at UCLA in March 1999, 11 early workers in the basic science or clinical practice of transplantation (or both) reached agreement on the most significant contributions of this era that ultimately made transplantation the robust clinical discipline it is today. These discoveries and achievements are summarized here in six tables and annotated with references.
Medullary Carcinoma of the Thyroid Gland
Authors: Wells Samuel A. , Franz Claudia
Published: August 2002

Medullary thyroid carcinoma (MTC) is an uncommon thyroid tumor that has attracted a great deal of interest because of its frequent presentation as a familial tumor and its primary involvement in the type II multiple endocrine neoplasia (MEN) syndromes MEN‐IIA and MEN‐IIB and familial medullary thyroid carcinoma (FMTC). The MTC tumor cells secrete the polypeptide hormone calcitonin, which serves as an excellent tumor marker, useful for defining the presence of disease, preoperatively or following thyroidectomy. The discovery that mutations in the RET proto‐oncogene are associated with MEN‐II syndromes was highly significant in that it demonstrated a clear correlation between genotype and phenotype; and most importantly it provided a mechanism whereby family members at risk could be identified by direct DNA analysis. Virtually all patients with MEN‐IIA, MEN‐IIB, and FMTC develop MTC; therefore there is a clear rationale for performing thyroidectomy as soon as a RET mutation has been identified. Because MTC appears to be much more aggressive in patients with MEN‐IIB, thyroidectomy is performed during the first year of life in this setting, whereas in patients with MEN‐IIA, where the tumor appears to be more indolent, the procedure can be safety delayed until age 5 years. Reoperative neck exploration in patients with evidence of persistent or recurrent MTC has been effective in a significant number of patients, although the success of the operation requires careful patient selection and preoperative assessment. MTC, as expressed in the MEN‐II syndromes, is an excellent model to evaluate the usefulness of interventional therapy in patients demonstrated to have a genetic predisposition for cancer.
Benefits of Endoscopic Vein Harvesting
Authors: Marty Bettina , von Segesser Ludwig Karl , Tozzi Piergiorgio , Guzmann Juan , Frascarolo Philippe , Muller Xavier , Hayoz Daniel
Published: August 2002

The purpose of this study was to evaluate and compare the benefits of endoscopic saphenous vein harvesting (EVH) with the traditional incision technique (TIT) for coronary artery bypass grafting (CABG) in respect to the technical procedure and clinical outcome. In a prospective nonrandomized, case‐matched study the greater saphenous vein was harvested for CABG in 22 patients using the endoscopic technique and in 18 patients with the traditional method. Comparisons were made for the operating time, length of incision and vein harvested, graft quality, postoperative complications, and pain assessment. Patient demographics were well matched. EVH required smaller incisions than did the TIT (10.5 ± 6.6 vs. 31.2 ± 7.8 cm, respectively; p < 0.0001). Harvest time and vein quality were comparable in the two groups. Total vein operating time was shorter following the endoscopic technique (60 ± 24 vs. 100 ± 35 minutes, respectively; p < 0.0001). EVH had fewer complications (NS), and postoperative pain was significantly less (p= 0.0034). The major advantages of endoscopic vein harvesting are a significant reduction of postoperative pain and strikingly better cosmetic results. Wound complications seem to be less frequent.
Supernumerary Parathyroid Glands: Frequency and Surgical Significance in Treatment of Renal Hyperparathyroidism
Authors: Pattou François N. , Pellissier Laurent C. , Noël Christian , Wambergue François , Huglo Damien G. , Proye Charles A.G.
Published: August 2002

Supernumerary parathyroid glands (SPGs) are found in 13% of random autopsies. The high incidence of SPGs could explain the persistence or trigger recurrence of renal hyperparathyroidism after surgery. The aim of this study was to assess the frequency and clinical relevance of SPG in patients operated on for renal hyperparathyroidism (HPT). In this retrospective study we reviewed the medical records of 290 patients with renal HPT who were initially treated in our department. We examined the anatomic and pathologic findings during cervical surgical exploration and the outcome of HPT during follow‐up. SPGs were identified in 87 patients (30%) during the initial cervicotomy, corresponding to intrathymic parathyroid cell islets (one to four) in 70 cases and to extrathymic SPG in 17 patients. Among 260 patients available for follow‐up, 11 experienced persistent HPT (4%), and 34 developed recurrent HPT (13%). A total of 25 patients were reoperated on, and SPGs were responsible for 4 of 8 cases of persistent HPT and 4 of 17 cases of recurrent HPT, representing an overall frequency of 32%. The anatomic distribution of SPGs found during reoperations included thymus, retroesophageal grove, carotid sheath, and mediastinum. SPGs are thus present in 30% of patients with renal HPT and are situated mainly in the thymus. Thymectomy should be performed routinely during the first surgical exploration to prevent recurrences arising from anterior mediastinal glands. SPGs were also responsible for 32% of persistent or recurrent HPT. In that setting, frankly ectopic SPGs are not rare, and preoperative imaging appears highly desirable prior to embarking on surgical reexploration.
Anatomic Dissociation between the Intrahepatic Bile Duct and Portal Vein: Risk Factors for Left Hepatectomy
Authors: Cheng Yu Fan , Huang Tung Liang , Chen Chao Long , Sheen‐Chen Shyr Ming , Lui Chun Chung , Chen Tai Yi , Lee Tze Yu
Published: August 2002

The anatomic variations of the intrahepatic portal vein and bile duct were analyzed to evaluate the potential risk of left hepatectomy. A total of 210 cholangiograms and hepatic arterioportograms were performed in which the ramifications of the intrahepatic portal vein and bile duct were investigated. The orientation of the intrahepatic duct and portal vein were classified into five types. In 175 patients (83.33%), the intrahepatic portal vein and bile duct had the same anatomic classification. In 24 patients (11.43%), the right anterior or posterior intrahepatic duct drained into the left hepatic duct at the umbilical portion (type IV); there were only 15 patients (7.14%) whose portal veins fell into this category. All patients with type IV portal veins had type IV hepatic ducts, but there were 9/49 patients (18.36%) whose hepatic duct distribution belonged to type IV but their portal veins belonged to type II (6 cases) or III (3 cases). Without complete knowledge of the intrahepatic portal and biliary anatomy, insufficient portal perfusion and bile duct complications may result from the left hepatectomy operation. Preoperative portal vein evaluation or left portal vein clamping can provide significant information, but there are still 18.36% of patients where type IV biliary ducts were not detected in those with type II and III portal veins. Cholangiography is of paramount importance in these two groups of patients, as it can prevent inadvertent injury to the right intrahepatic ducts, which drain into the left intrahepatic duct. On the other hand, intraoperative ultrasonography is recommended to identify or exclude an aberrant portal vein if type VI biliary anatomy is detected during intraoperative cholangiography.
Close Correlation between Increased Sialyl‐Lewisx Expression and Metastasis in Human Gastric Carcinoma
Authors: Ura Hideki , Denno Ryuichi , Hirata Koichi , Yamaguchi Koji , Yasoshima Takahiro , Shishido Takayuki
Published: August 2002

Expression of sialyl‐Lewisx
(sLex) antigen was studied immunohistochemically in 110 resected human gastric carcinomas using an anti‐sLex
monoclonal antibody. Lymph node, liver, and peritoneal metastases were clearly more prevalent in tumors expressing high levels of sLex than in those with no or low‐level sLex
expression. No correlation was found between sLex
expression and histologic grade or histologic type of the Lauren classification. Among the tumors with lymph node metastasis, 44%
expressed high levels of sLex in both the primary tumor and involved lymph nodes, and 14% of the metastatic lesions demonstrated increased sLex expression. The 5‐year survival rate of the patients undergoing complete (R0) gastric resections was 60% in the sLex high‐expression group, which was significantly lower than that of the sLex low‐expression group (81%) and of the no‐expression group (87%) (p < 0.05). These results suggest that high‐level sLex expression is related to both an increased risk of metastasis and poor prognosis in gastric cancer patients.
Increased Serum Interleukin‐8: Correlation with Poor Prognosis in Patients with Postoperative Multiple Organ Failure
Authors: Hamano Kimikazu , Gohra Hidenori , Noda Hiroshi , Katoh Tomoe , Fujimura Yoshihiko , Zempo Nobuya , Esato Kensuke
Published: August 2002

This study investigated whether cytokines and colony‐stimulating factors can predict prognosis in patients with postoperative multiple organ failure (MOF). We evaluated 14 patients with postoperative MOF who underwent operation for cardiovascular disease. Seven patients recovered from MOF (survivors) and seven did not recover and died (nonsurvivors). The white blood cell (WBC) count, granulocyte colony‐stimulating factor, monocytic colony‐stimulating factor, interleukin‐6 (IL‐6), and IL‐8 were measured on the day the patients were judged to be in MOF and each week thereafter until the patients recovered or died. Survivors and nonsurvivors were equivalent in terms of age, gender, proportion of use of extracorporeal circulation, operation time, volume of blood transfusion, time from operation to the onset of MOF, the MOF score, proportion of bacteremia, duration of MOF, and number of failed organs. The mean duration of MOF was less than 2 weeks in both groups; therefore the measurements were compared on the first day of MOF and 1 week later. No significant differences between the two groups in terms of WBC counts, colony‐stimulating factors, and IL‐6 levels were noted. However, the serum level of IL‐8 was significantly higher in nonsurvivors than in survivors. Patients with a high serum levels of IL‐8 at the time of MOF had a poor prognosis.
Issues in Surgical Randomized Controlled Trials
Authors: McLeod Robin S.
Published: August 2002

As technology expands and health care resources become more limited, there is increasing pressure on surgeons to evaluate surgical procedures and technology to ensure they are effective. No longer is evidence from case series acceptable, and treatments must be evaluated in randomized controlled trials. The power of the randomized controlled trial is that because of its rigorous design the risk of random or systematic (bias) error is minimized and thus the risk of making an incorrect conclusion about the efficacy of a treatment is minimized. The randomized controlled trial has been widely accepted for evaluating the efficacy of medical treatments but less so for surgical procedures. Many cite methodologic issues related to surgical issues as the reason for this, including concerns related to standardization of the surgical procedure, timing of surgical trials, difficulties with blinding of subjects and investigators, ethics of surgical trials, and patient and surgeon acceptance of surgical trials. These issues are discussed in this paper as are possible strategies to minimize their effect.
Tumors of the Esophagus
Authors: Hatch George F. , Wertheimer‐Hatch Laura , Hatch Kathryn F. , Davis Gregory B. , Blanchard D. Kay , Foster Roger S. , Skandalakis John E.
Published: August 2002

This collective review includes all available case reports of smooth muscle (stromal) tumors of the esophagus in the world literature. Compiling this review, we endeavored to examine cumulative and recently collected data of both benign and malignant esophageal smooth muscle tumors found in the literature spanning the period from 1875 to 1996, which totaled 1679 leiomyomas (LMs) and 165 leiomyosarcomas (LMSs). The peak age of occurrence of benign smooth muscle tumors in the esophagus was found to be between the ages of 30 and 59, whereas the highest frequency of malignant tumors was seen later in life, during the decade from age 60 to 69. The most common location of both LMs and LMSs was the lower third of the esophagus. Their patterns of growth differed; LMs were more likely to grow intramurally, and LMSs were predominantly intraluminal. Most patients with LMs presented with dysphagia and pain or discomfort; patients with LMSs additionally commonly complained of weight loss. As with smooth muscle tumors of other areas of the gastrointestinal tract, the duration of symptoms averaged 1 month to 1 year, and malignant tumors grew to larger sizes than benign neoplasms. Approximately one‐third of LMSs had metastasized at diagnosis, and there was a 5‐year survival rate of approximately 20%.
Rapid evolution of larval development time during mass‐rearing in the melon fly, Bactrocera cucurbitae
Authors: Miyatake Takahisa , Yamagishi Masaaki
Published: August 2002

A quantitative genetic analysis of rapid evolution of a life history trait has been conducted on the first 24 generations of mass‐rearing in the melon fly Bactrocera cucurbitae (Coquillett) (Diptera: Tephritidae). The phenotypic variance of larval development time in each generation was divided into genetic and residual components. Mean and phenotypic coefficients of variation of larval development time decreased gradually as generations proceeded as a result of artificial selection for shorter larval period in the mass‐rearing procedure. There was a trend that additive genetic coefficients of variation in larval development time decreased with generations. These changes are entirely attributed to genetic responses to laboratory selection under the mass‐rearing environment because the population was maintained at a very large size so as to exclude random genetic drift and inbreeding depression, which would be other factors responsible for the observed genetic changes. The residual coefficients of variation in larval development time did not change with generations. Realized heritability of larval development time was low. The heritabilities for larval development time estimated from parent–offspring regression at generations 60 and 70, when the evolutionary plateau was asymptotically reached, were not significantly larger than 0.
Postreperfusion biopsies are useful in predicting complications after liver transplantation
Authors: Busquets Juli , Figueras Juan , Serrano Teresa , Torras Jaume , Ramos Emilio , Rafecas Antonio , Fabregat Juan , Lama Carmen , Xiol Xavier , Baliellas Carme , Jaurrieta Eduardo
Published: August 2002

Biliary complications after orthotopic liver transplantation (OLT) may occur because of preservation injury (PI). In this study, we examine findings on routine reperfusion biopsy specimens in relation to the occurrence of biliary complications and graft outcome. From 1997 to 2000, a total of 193 OLTs were performed in our center. Postreperfusion biopsy specimens were analyzed and histological lesions were graded. For analysis, grafts were grouped into 2 categories: the presence or absence of PI (severe to moderate lesions versus mild or no lesions). Histological evidence of PI was present in 17% of the biopsy specimens. The incidence of grafts with PI and ischemia time longer than 12 hours was 38% compared with 14% in PI and short ischemia time (P = .02). Biliary complications were also more frequent in the PI group (28% v 14%; P = .03). Study of risk factors by means of logistic regression analysis confirmed that the PI group had a greater risk for biliary complications (relative risk, 2.8; 95% confidence interval, 1 to 7.4; P = .03). Moreover, moderate macrovesicular steatosis was found in 6% of the grafts, resulting in a 40% graft loss rate. We found that an increased presence of neutrophilic infiltrates in the postreperfusion biopsy specimen, indicating PI, was related to an increased incidence of biliary complications. Moreover, moderate macrovesicular steatosis was associated with increased graft loss. Therefore, postreperfusion biopsies are useful in anticipating post-OLT complications.
The use of hepatitis C viral RNA levels in liver tissue to distinguish rejection from recurrent hepatitis C
Authors: Gottschlich Michelle J. , Aardema Kay L. , Burd Eileen M. , Nakhleh Raouf E. , Brown Kimberly A. , Abouljoud Marwan S. , Hirst Kathryn , Moonka Dilip K.
Published: August 2002

Persistence of hepatitis C virus (HCV) after orthotopic liver transplantation is almost universal in HCV-infected patients. Histological examination of liver biopsy specimens can be variable in distinguishing between recurrent hepatitis C and acute cellular rejection. The purpose of this study is to determine whether hepatic HCV RNA levels can be used to distinguish rejection from recurrent HCV by determining whether hepatic HCV RNA levels correlate with histological characteristics and clinical course. Seventy-two biopsy specimens were evaluated from 36 liver transplant recipients with HCV and elevated liver-related enzyme levels. Based on histological findings and clinical response to therapy, patients were defined as belonging to 1 of 5 groups: (1) definite rejection, (2) probable rejection, (3) indeterminate findings, (4) probable HCV, and (5) definite HCV. Hepatic HCV RNA was quantified using the Amplicor Monitor assay (Roche Diagnostic Systems Inc, Branchburg, NJ). There was a difference across groups in HCV RNA levels (P = .046). The median HCV RNA level was 10,695 copies/mg of tissue DNA in the definite-HCV group compared with 1,024 copies/mg of tissue DNA in the definite-rejection group. Using pairwise comparisons, significant differences were found between definite HCV and definite rejection, probable HCV and definite rejection, probable HCV and probable rejection, and probable HCV and indeterminate. Our findings support the following conclusions. (1) In liver transplant recipients, hepatic HCV RNA levels are statistically greater in patients with recurrent HCV than rejection, although there is considerable overlap between groups. (2) Patients with low HCV RNA levels were unlikely to have recurrent HCV. (3) Patients with minimal and indeterminate findings on biopsy (group 3) had low HCV RNA levels.
Cryptogenic cirrhosis and posttransplantation nonalcoholic fatty liver disease
Authors: Ong Janus , Younossi Zobair M. , Reddy Vishnu , Price Lori Lyn , Gramlich Terry , Mayes James , Boparai Navdeep
Published: August 2002

Some patients diagnosed with cryptogenic cirrhosis may have “burned-out” nonalcoholic fatty liver disease (NAFL). To test this hypothesis, we used our liver transplant database (November 1984 to November 1998) to assess the incidence of NAFL in patients with cryptogenic cirrhosis after orthotopic liver transplantation (OLT). We also examined the clinicodemographic features associated with post-OLT NAFL, obtained by chart review and telephone interviews. When available, post-OLT liver biopsy specimens were reviewed blindly by a hepatopathologist according to the NAFL pathology protocol. We identified 51 patients with cryptogenic cirrhosis (mean age, 51 ± 12 years); 60% were women, 94% were white, and 34% had type 2 diabetes mellitus (DM). Mean pre-OLT body mass index (BMI) was 27.33 ± 5.54 kg/m2. Twenty-five patients underwent at least 1 post-OLT liver biopsy. Post-OLT NAFL was identified in 13 patients (25.4%), whereas post-OLT nonalcoholic steatohepatitis (NASH) was seen in 8 patients (15.7%). Features associated with post-OLT NASH were pre- and post-OLT type 2 DM (P ≤ .05) and an elevated fasting triglyceride level (P < .05). BMI tended to be greater in patients with post-OLT NAFL or NASH. Those who did not develop post-OLT NAFL showed a decrease in BMI. Patients with cryptogenic cirrhosis undergoing OLT resemble patients with NAFL. Post-OLT NAFL and NASH can be seen in a number of patients with cryptogenic cirrhosis. This supports the notion that some cases of cryptogenic cirrhosis represent burned-out NAFL.
Technical challenges of hepatic venous outflow reconstruction in right lobe adult living donor liver transplantation
Authors: Ghobrial Rafik M. , Hsieh Chung-Bao , Lerner Susan , Winters Sharon , Nissen Nicholas , Dawson Sherfield , Amersi Farin , Chen Pauline , Farmer Douglas , Yersiz Hasan , Busuttil Ronald W.
Published: August 2002

A right lobe graft that is drained by the right hepatic vein (RHV) is obtained by transecting the liver on the right side of the middle hepatic vein (MHV). On occasion, a small RHV that only drains a portion of the right lobe, with the predominant outflow achieved by the MHV, is encountered. If such variation is not recognized while performing right lobe liver transplantation and the RHV only is used for reconstruction, venous outflow obstruction with subsequent graft congestion and eventual graft failure will occur. Additionally, preservation of the main MHV and its branch drainage of the left lobe is crucial to avoid outflow blockage to the remaining segment 4 in the donor. We report 4 cases showing a variant type of small RHV and large MHV branch that drain not only segments 5 and 8, but also segments 6 and 7. These variations were simultaneously associated with a large-caliber inferior RHV that also required reconstruction. The methods used to diagnose such anatomic variations and the techniques for reconstruction in the donor and recipient are described.
Life-threatening hypophosphatemia after right hepatic lobectomy for live donor adult liver transplantation
Authors: Pomposelli James J. , Pomfret Elizabeth A. , Burns David L. , Lally Ann , Sorcini Andrea , Gordon Fredric D. , Lewis David W. , Jenkins Roger
Published: August 2002

Life-threatening hypophosphatemia (phosphorus < 1.0 mg/dL) has been reported only once after liver resection for tumor and was associated with a significant increase in postoperative complications. Hypophosphatemia is associated with reversible cardiac dysfunction, hypoventilation, and impaired immunity. The purpose of this study was to determine the incidence of hypophosphatemia after elective right hepatic lobectomy for live donor adult liver transplantation (LDALT), investigate the associated complication rate and surgical outcome of live liver donors, and determine the efficacy of prospective treatment with phosphate repletion as part of total parenteral nutrition (TPN). Evaluation of 30 donors who provided 30 right-lobe grafts between December 1998 and January 2000 was performed. Of the initial 18 live liver donors (group 1), 10 donors were treated with TPN that contained slightly more (35 ± 8 mmol/d) than the recommended daily allowance (RDA) of phosphorus (30 mmol/d) starting on postoperative day 1. The last 12 donors (group 2) were prospectively studied and administered similar TPN with 2 times the RDA for phosphorus (60 mmol/d). All donors in group 1 developed hypophosphatemia that was either life threatening (phosphorus < 1.0 mg/dL) in 70% or severely depleted (phosphorus, 1.5 to 1.1 mg/dL) in 30%. With more aggressive phosphate repletion (group 2), only 8% developed life-threatening (phosphorus < 1.0 mg/dL) hypophosphatemia and 30% developed severe (phosphorus, 1.1 to 1.5 mg/dL) hypophosphatemia. Results suggest that hypophosphatemia is a universal event after LDALT and may have contributed to the observed complications in this study. Repletion of phosphorus at twice the RDA abrogates the incidence of hypophosphatemia and may reduce donor morbidity. Institutions performing LDALT should carefully monitor live liver donors for hypophosphatemia and correct abnormal phosphate levels. Additional studies are needed to determine whether more aggressive parenteral repletion can prevent postoperative hypophosphatemia and thus improve outcomes.