bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a method for the direct analysis of peptide AM336 in monkey cerebrospinal fluid using liquid chromatography/electrospray ionization mass spectrometry with a mixed‐function column
Authors: Bu Wei , Freer Scott D. , Hollar Shelly M. , Stetson Philip L. , Boyd Robert A. , Kurek John B. , Sved Daniel W.
Published: October 2003

A liquid chromatography/mass spectrometry (LC/MS) analytical procedure, using a single column for sample clean‐up, enrichment and separation, has been developed for the determination of the peptide AM336 in monkey cerebrospinal fluid (CSF). CSF samples were injected and analyzed using a polymer‐coated mixed‐function high‐performance liquid chromatography (HPLC) column with gradient elution and application of a timed valve‐switching event. The mass spectrometer was operated in the positive electrospray ionization (ESI+) mode with single ion recording (SIR) at m/z 920. The method was validated, yielding calibration curves with correlation coefficients greater than 0.9892. Assay precision and accuracy were evaluated by direct injection of AM336‐fortified CSF samples at three concentration levels. Analyzed concentrations ranged from 99.93 to 113.1% of their respective theoretical concentrations with coefficients of variation below 9.0%. An evaluation of the signal‐to‐noise (S/N) ratio for a 200 ng/mL calibration standard, considered to be the lower limit of quantitation (LLOQ), resulted in an estimated limit of detection (LOD) of 31.2 ng/mL. Preliminary data suggest the possibility of using this method to analyze AM336 also in plasma samples, pending the successful outcome of additional investigations. Copyright © 2003 John Wiley & Sons, Ltd.
Parallel determination of multiple protein metabolite interactions using cell extract, protein microarrays and mass spectrometric detection
Authors: Morozov Victor N. , Morozova Tamara Ya. , Johnson Kenneth L. , Naylor Stephen
Published: October 2003

Analysis of interactive networks between proteins and other molecular constituents is of paramount importance to delineate complex cellular processes. In order to facilitate this process, new technologies that allow rapid, high‐throughput parallel screening, as well as identification of constituents, are necessary. A particularly powerful combination in this regard could be the use of multiprotein microarrays coupled with mass spectrometry (MS). In the initial step of the method development we applied MS to single‐protein microarrays. We demonstrated that even a simplified version of the method allows rapid parallel label‐free assay of specific protein interactions with multiple metabolites derived from complex artificial and natural mixtures. The microarrays fabricated by the electrospray deposition technique and cross‐linked in glutaraldehyde vapor were brought into contact with droplets of solution containing either a natural extract of baker's yeast cells or an artificial cocktail of metabolites. After washing, the microarrays were placed into 75% methanol to denature proteins and release specifically bound metabolites. The eluates were then analyzed by electrospray ionization mass spectrometry (ESI‐MS) to simultaneously detect all the metabolites bound. Such a procedure applied to ten different proteins demonstrated that 50–400 ng of cross‐linked protein is enough to obtain ion intensities from metabolites that are well distinguishable above noise. The compatibility of microplates and different microarray designs with MS detection is discussed. Copyright © 2003 John Wiley & Sons, Ltd.
Robust H∞ control for uncertain singular systems with state delay
Authors: Xu Shengyuan , Lam James , Yang Chengwu
Published: October 2003

This paper addresses the problem of robust H∞ control for uncertain continuous singular systems with state delay. The singular system under consideration involves state time delay and time‐invariant norm‐bounded uncertainty. Based on the linear matrix inequality (LMI) approach, we design a memoryless state feedback controller law, which guarantees that, for all admissible uncertainties, the resulting closed‐loop system is not only regular, impulse free and stable, but also meets an H∞‐norm bound constraint on disturbance attenuation. A numerical example is provided to demonstrate the applicability of the proposed method. Copyright © 2003 John Wiley & Sons, Ltd.
Robust Kalman filtering for uncertain discrete‐time linear systems
Authors: Garcia Germain , Tarbouriech Sophie , Peres Pedro L. D.
Published: October 2003

This paper presents a steady‐state robust state estimator for a class of uncertain discrete‐time linear systems with norm‐bounded uncertainty. It is shown that if the system satisfies some particular structural conditions and if the uncertainty has a specific structure, the gain of the robust estimator (which assures a guaranteed cost) can be calculated using a formula only involving the original system matrices. Among the conditions the system has to satisfy, the strongest one relies on a minimum phase argument. It is also shown that under the assumptions considered, the robust estimator is in fact the Kalman filter for the nominal system. Copyright © 2003 John Wiley & Sons, Ltd.
Characterizing the solution set of polynomial systems in terms of homogeneous forms: an LMI approach
Authors: Chesi G. , Garulli A. , Tesi A. , Vicino A.
Published: October 2003

This paper considers the problem of determining the solution set of polynomial systems, a well‐known problem in control system analysis and design. A novel approach is developed as a viable alternative to the commonly employed algebraic geometry and homotopy methods. The first result of the paper shows that the solution set of the polynomial system belongs to the kernel of a suitable symmetric matrix. Such a matrix is obtained via the solution of a linear matrix inequality (LMI) involving the maximization of the minimum eigenvalue of an affine family of symmetric matrices. The second result concerns the computation of the solution set from the kernel of the obtained matrix. For polynomial systems of degreeminnvariables, a basic procedure is available if the kernel dimension does not exceedm+1, while an extended procedure can be applied if the kernel dimension is less thann(m−1)+2. Finally, some application examples are illustrated to show the features of the approach and to make a brief comparison with polynomial resultant techniques. Copyright © 2003 John Wiley & Sons, Ltd.
Sustainability assessment in the German detergent industry: from stakeholder involvement to sustainability indicators
Authors: Seuring Stefan A. , Koplin Julia , Behrens Torsten , Schneidewind Uwe
Published: October 2003

Since the early years of environmentalism, the detergent industry has been under pressure from NGOs and consumers. While the path towards an integrated product policy has been set, further developments towards sustainability are necessary.

In a project conducted by the University of Oldenburg in cooperation with the German Detergent Manufacturers Association (IKW), future potentials for sustainable development were investigated. From this, a set of indicators was developed.

This paper will review the project methodology, where a stakeholder assessment plays a key role, and present some findings. Stakeholder interviews and two workshops allowed discovery of the central issues to be tackled by the German detergent industry.

The environmental product life‐cycle and stakeholder concept provide the theoretical basis for the so called sustainability matrices, one each for the environmental, economic and social dimensions. These matrices were used to facilitate discussions regarding relevant sustainability issues and indicators. Copyright © 2003 John Wiley & Sons, Ltd and ERP Environment.
Sustainable business versus sustainable environment: a case study of the Hong Kong shark fin business
Authors: Cheung Gordon C.K. , Chang Chak Yan
Published: October 2003

This study attempts to use the shark fin business in Hong Kong as a case to illustrate its challenge to international sustainability and global environmental governance. Regarding the commercial fishing of sharks and the degradation of the species, the paper begins with a survey of characteristics of sharks in the world and the responses from the international environmental agents. The authors will then detail their statistical findings, together with interviews with the shark fin manufacturers in Hong Kong. Their study began in 1999 and the statistical data ran from 1977 to 2001. Finally, the so‐called ‘foodway’ in the consumption of shark fin will be discussed with a view to the international concerns over endangered species in general and sharks in particular. Copyright © 2003 John Wiley & Sons, Ltd and ERP Environment.
Adaptive secure software architecture for electronic commerce
Authors: Tak Sung Woo , Park Eun Kyo
Published: October 2003

As Internet business exponentially grows, a need for the high security level categories that identify a group of connections or an individual transaction is manifest. Recently the development of efficient and secure software architecture has been in high demand. In this paper, we propose adaptive secure software architecture to support secure e‐commerce transactions. Our adaptive secure software architecture dynamically adapts security classes based on the nature and sensitivity of interactions among participants. Four security classes incorporate security levels of cryptographic techniques with a degree of information sensitivity. We have done extensive experiments on the performance of the proposed adaptive secure software architecture. Experimental results show that our adaptive secure software architecture provides e‐commerce transactions with high‐quality security services. Copyright © 2003 John Wiley & Sons, Ltd.
System and software designs for transaction processing in asymmetric communication environments
Authors: Huang Y. , Lee Y. H.
Published: October 2003

Observing that it is impractical to use traditional methods to control concurrency in broadcast‐based asymmetric communication environments, we introduce a concurrency control protocol designed for broadcast‐based transaction processing called Server Timestamp and Update Broadcast Supported Concurrency (STUBcast). STUBcast supports two new correctness criteria proposed in this paper—Single Serializability and Local Serializability. These criteria are weaker than global serializability, but are practical and easier to achieve in broadcast environments. This article also discusses the software design for the simulation program and the protocol implementation. Simulation results collected using our simulation program suggest that STUBcast could be very efficient in realistic application environments. Copyright © 2003 John Wiley & Sons, Ltd.
Leveraging emerging network services to scale multimedia applications
Authors: Calvert K. , Griffioen J. , Mullins B. , Natarajan S. , Poutievski L. , Sehgal A. , Wen S.
Published: October 2003

Multicast services have been used to transmit multimedia data to large receiver groups. Only recently have counterpart network services been introduced to provide similar scalability and anonymity in the opposite direction (i.e. messages from a group of senders destined for a common receiver).

In this paper, we explore how these many‐to‐one services, specifically the concast service, can be used to improve the scalability and performance of multimedia applications. In particular, we show how such services can be used in both the control and data planes to overcome well‐known scalability problems (e.g. with Real Time Protocol) that are difficult to solve effectively with end‐system approaches alone. We validate our solutions by presenting experimental results taken from prototype video and audio applications we designed and implemented. Our initial results show substantial reductions in congestion‐induced loss using these generic services. Copyright © 2003 John Wiley & Sons, Ltd.
Directly linked porphyrin arrays
Authors: Aratani Naoki , Osuka Atsuhiro
Published: October 2003

The AgI‐promoted oxidative meso–meso coupling reaction of 5,15‐diaryl ZnII‐porphyrin was serendipitously found in the course of our synthetic approaches towards photosynthetic reaction centers. Based on this reaction, a variety of directly linked and fused porphyrin arrays have been synthesized, including linear meso–meso‐linked porphyrin arrays, windmill‐ and grid‐shaped porphyrin arrays, meso–β singly linked diporphyrins, β–β linked diporphyrins, meso–β doubly linked (fused) diporphyrins and oligoporphyrins, meso–meso β–β doubly linked (fused) diporphyrins, and meso–meso β–β–β–β triply linked (fused) diporphyrins. The meso–meso coupling reaction of 5,15‐diaryl ZnII‐porphyrins is advantageous considering its high regioselectivity as well as its ease of extension to large porphyrin arrays as is demonstrated by the synthesis of a discrete meso–meso‐linked 128‐mer and poly(5,15‐porphyrinylene). Finally, the oxidation of end‐phenyl capped meso–meso‐linked zinc porphyrins with DDQ‐Sc(OTf)3 gave π‐conjugated flat porphyrin tapes. To the best of our knowledge, the meso–meso linked 128‐mer is the longest man‐made discrete molecule, and the porphyrin tape 12‐mer is the most extensively conjugated porphyrin array, as evinced by the lowest electronic band peak at 3500 cm−1. © 2003 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 3: 225–234; 2003: Published online in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/tcr.10062
The repetitive C‐terminal domain of RNA polymerase II: Multiple conformational states drive the transcription cycle
Authors: Lin Patrick S. , Tremeau‐Bravard Alexandre , Dahmus Michael E.
Published: October 2003

RNA polymerase (RNAP) II is a complex multisubunit enzyme responsible for the synthesis of mRNA in eukaryotic cells. The largest subunit contains at its C‐terminus a unique domain, designated the CTD, comprised of tandem repeats of the consensus sequence Tyr1Ser2Pro3Thr4Ser5Pro6Ser7. This repeat occurs 52 times in mammalian RNAP II. The CTD is subject to extensive phosphorylation at specific points in the transcription cycle by distinct CTD kinases that phosphorylate certain positions within the consensus repeat. The level and pattern of phosphorylation is determined by the concerted action of CTD kinases and CTD phosphatases. The highly dynamic modification by multiple CTD kinases and phosphatases generate distinct conformations of the CTD that facilitate the recruitment of specific macromolecular assemblies to RNAP II. These CTD interacting proteins influence formation of a preinitiation complex at the promoter and couple processing of the primary transcript to the elongation complex. © 2003 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 3: 235–245; 2003: Published online in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/tcr.10063
Determination of some rare earth elements by EDXRF and artificial neural networks
Authors: Schimidt Fernando , Cornejo‐Ponce Lorena , Bueno Maria Izabel M. S. , Poppi Ronei J.
Published: October 2003

This paper describes the simultaneous determination of Pr, Nd and Sm by EDXRF spectrometry using mixtures of oxides of these metals in a silica matrix. The data were treated by distinct neural network algorithms: back‐propagation (BP), Levenberg–Marquardt (LM) and two variations of back‐propagation (called BP‐SC, single component, and BP‐MC, multiple component), using results from the PLS model (partial least square regression) for comparison. The best applied model was the BP‐SC neural network, which produced relative standard errors of prediction of 17.5% for Pr, 12.5% for Nd and 12.6% for Sm. Copyright © 2003 John Wiley & Sons, Ltd.
Implementation of a spectrum fitting procedure using a robust peak model
Authors: Van Gysel M. , Lemberge P. , Van Espen P.
Published: October 2003

The need for an accurate description of characteristic x‐ray lines has led to the development of complex peak models that combine a Gauss, a shelf and a tail function. Via relationships that describe the shelf and tail parameters as a function of the energy, it is possible to reduce the number of fit parameters significantly. In this work, we carried out an experiment to study the shelf and tail parameters obtained with an HPGe detector. We observed a strong discontinuity in the shelf and tail parameters around the K‐edge energy of Ge. This indicates that these parameters are strongly dependent on the mass‐attenuation coefficient of the detector material. Therefore, we propose relationships that describe those parameters as a function of the energy and the mass‐attenuation coefficient. The implementation of these relationships in a fitting procedure results in a more robust fitting procedure with a much smaller number of fitting parameters. Excellent fits for HPGe spectra can be obtained. Because the detector dependence seems to be fairly general, we could successfully apply the model to Si(Li) spectra also. Copyright © 2003 John Wiley & Sons, Ltd.
Numerical description of photoelectric absorption coefficients for fundamental parameter programs
Authors: Ebel Horst , Svagera Robert , Ebel Maria F. , Shaltout Abdallah , Hubbell John H.
Published: October 2003

After a systematic analysis of different databases and a comparison with empirical data, we decided to describe photoelectric absorption coefficients, coherent and incoherent scattering coefficients and mass attenuation coefficients in the energy range from 1 to 300 keV for elements from Z = 1 to 94 by a modified version of Scofield's tables in combination with scattering coefficients from Elam et al. Modifications include check and correction of edge positions, description of M4‐ and M5‐ranges of elements from promethium upwards by sawtooth responses and reduction of data by introduction of least‐squares fits of fifth order to Scofield's and Elam et al.'s numerical data. Our database was developed especially for application in fundamental parameter programs for quantitative x‐ray analysis (XRFA, EPMA, XPS and TEY). Copyright © 2003 John Wiley & Sons, Ltd.
Preparation of calibrating standards for x‐ray fluorescence spectrometry of trace metals in plastics
Authors: Nakano Kazuhiko , Nakamura Toshihiro
Published: October 2003

Convenient x‐ray fluorescent spectrometry was developed for the determination of V, Cr, Co, Ni, Ge and Sb in plastic materials. The calibrating standards were prepared by casting of polyurethane or polyester including a xylene solution of organometallic compounds as a standard. The calibrating disk had a homogeneous elemental distribution and excellent durability. The calibration curves of six elements showed a good linearity of less than 50 mass ppm for V and Ni, 100 mass ppm for Co and Ge, 200 mass ppm for Cr, and 400 mass ppm for Sb. The lower limits of detection (3σ) of the present method were 0.19 mass ppm for V, 0.42 for Cr, 0.24 for Co, 0.18 for Ni, 0.066 for Ge, and 2.1 for Sb. The proposed method has been applied to several different industrial plastics. The quantitative results are in good agreement with those obtained by the AAS method and x‐ray fluorescent spectrometry using the fundamental parameter calculation method. Copyright © 2003 John Wiley & Sons, Ltd.
Role of antioxidant enzymatic defences against oxidative stress (H2O2) and the acquisition of oxidative tolerance in Candida albicans
Authors: González‐Párraga Pilar , Hernández José A. , Argüelles Juan Carlos
Published: October 2003

In Candida albicans, trehalose plays an essential role as a protector of cell integrity against oxidative challenge. A double homozygous mutant, tps1/tps1, deficient in trehalose synthesis, displayed severe cell mortality when exposed to high H2O2 concentrations, compared with its congenic parental (CAI‐4) strain (Alvarez‐Peral et al., 2002). We have examined the putative role of a set of well‐known antioxidant enzymes as components of the defence mechanism against oxidative challenges. When exposed to mild non‐lethal oxidative treatment (0.5 mM H2O2), a significant induction of catalase, glutathione reductase (GR), and Cu,Zn‐superoxide dismutase (SOD) was recorded in tps1/tps1 exponential cultures. However, in CAI‐4 cells, subjected to the same conditions, there was only a clear activation of catalase, Mn‐SOD and Cu,Zn‐SOD activities. The degree of activation was always much more pronounced in the trehalose‐deficient mutant than in its wild‐type counterpart, except for Mn‐SOD activity. After exposure to severe oxidative stress (50 mM H2O2) only GR and catalase activities increased in tps1/tps1 cultures, whereas in CAI‐4 cells GR but not catalase was induced. In both cell strains, 50 mM H2O2 caused inhibition of the Mn‐ and Cu,Zn‐SOD isozymes, this inhibition being more pronounced in tps1/tps1 cells. C. albicans is able to acquire adaptive oxidative tolerance by pretreatment with a low non‐stressing concentration of H2O2 before exposure to a drastic oxidative challenge. When these antioxidant activities were measured during the adaptive response, a greater degree of enzymatic antioxidant induction was consistently observed in the tps1/tps1 mutant with respect to the CAI‐4 strain. Together with a higher intrinsic sensitivity of tps1/tps1 cells, we suggest that this unexpected increase might be explained in terms of a compensatory mechanism to overcome the lack of endogenous trehalose upon drastic oxidative exposure, although this induction was not sufficient to improve the percentage of cell viability. Copyright © 2003 John Wiley & Sons, Ltd.
Axillary Node Sample to Evaluate the Axilla
Authors: Chetty Udi
Published: October 2003

Lymphatic drainage from the breast is principally to the ipsilateral axilla. In patients with breast cancer the status of the lymph nodes in the axilla is an important prognostic factor and can be used to determine local and systemic therapies. Clinical assessment of the axillary lymph nodes is unreliable, and imaging techniques, although they show some promise, are at present not practical. Standard policy for management of the axilla is clearance of the axillary lymph nodes (either level II or level III), which is justified on the grounds that it both stages and treats the axilla. In those who are axillary node‐negative, however, it is an unnecessary operation and is associated with some morbidity. Various methods to obtain lymph nodes for histologic assessment in an attempt to stage the axilla have been tried. The pectoral node biopsy, where a single node is removed from the axillary tail, has been shown to be unreliable. A triple‐node biopsy (pectoral node, apical node, internal mammary node) provides excellent prognostic data but is difficult to perform in patients who have been treated by breast conservation. The four‐node sampling technique has been evaluated in Edinburgh in two randomized trials comparing node sampling to level III axillary clearance. It was shown to be reliable for staging the axilla; and in those who are node‐negative no further treatment is required. Detailed morbidity has been assessed in patients who underwent axillary clearance; and node sampling plus radiotherapy and node sampling without radiotherapy showed that those with node sampling had the least morbidity. Those who had node sampling plus radiotherapy have reduced movement around the shoulder joint, and the axillary clearance group have increased swelling of the upper limb and slightly reduced abduction. The sentinel node biopsy is presently being assessed in several centers by randomized studies. Several large series have shown the technique to be accurate (98%) when the sentinel node is identified (around 90% of cases).
Lymphoscintigraphy and Lymphatic Mapping for Identification of Sentinel Lymph Nodes
Authors: Hsueh Eddy C. , Turner Roderick R. , Giuliano Armando E.
Published: October 2003

The recently introduced technique of sentinel lymph node dissection (SLND) may replace complete axillary lymph node dissection for axillary staging of early breast cancer. Successful SLND is predicated on meticulous delineation of the lymphatic pathway and sentinel node(s). Currently employed lymphatic mapping materials include vital blue dyes and radioactive tracers. Techniques of intraoperative lymphatic mapping and SLND using dye, tracer, or both have high success rates in the hands of experienced investigators, but their routine and widespread use awaits resolution of questions about the timing, dose, and type of radioactive tracer; the optimal lymphatic mapping technique; indications and contraindications for SLND; and certification of qualified surgeons, pathologists, and nuclear medicine physicians.
Pathologic Examination of Sentinel Lymph Node for Breast Carcinoma
Authors: Turner Roderick R. , Giuliano Armando E. , Hoon Dave S.B. , Glass Edwin C. , Krasne David L.
Published: October 2003

Comprehensive pathologic evaluation of the sentinel lymph node using step sections and cytokeratin immunohistochemistry enhances detection of micrometastases and optimizes the staging of breast carcinoma. This review discusses our current understanding of the pathologic and molecular techniques for sentinel node examination.
Sentinel Node Biopsy in Breast Cancer: ALMANAC Trial
Authors: Clarke Dayalan , Khonji Nader I. , Mansel Robert E.
Published: October 2003

Sentinel node biopsy of breast cancer is becoming an increasingly popular topic. The concept of the sentinel node being the first lymph node to contain metastatic cancer within a tumor’s lymphatic basin was introduced by Cabanas, a South American surgeon, following his work on carcinoma of the penis. Morton and his colleagues then applied this principle to malignant melanomas, and more recently this concept has gained popularity for carcinoma of the breast. In breast cancer patients, the fact that a sentinel node can be localized and the suggestion that the sentinel node is representative of the axillary nodal status has been confirmed by a number of studies across the world. Most authors writing on this subject, however, end with a caution that the results of randomized trials are needed before this new surgical technique can be accepted as part of routine breast cancer management. The Medical Research Council of the United Kingdom has funded the audit phase of a multicenter, two phase, randomized trial called the Axillary Lymphatic Mapping Against Nodal Axillary Clearance (ALMANAC) trial, which will compare standard axillary management with sentinel node‐guided axillary management. The aims and protocol of the trial are discussed in detail here.
Hepatic Metastases of Gastroenteropancreatic Neuroendocrine Tumors: Safe Hepatic Surgery
Authors: Jaeck Daniel , Bachellier Philippe , Lemarque Pascal , Weber Jean‐Christophe , Nakano Hiroshi , Wolf Philippe
Published: October 2003

Liver metastases of neuroendocrine tumors are usually slow‐growing, and cytoreductive hepatectomy can help reduce the effects of endocrinopathies and increase life expectancy and symptom‐free survival. However, it has yet to be fully investigated how hepatectomy for metastatic neuroendocrine tumors can be performed safely. Here we report the results of 13 patients with neuroendocrine liver metastases operated on in our institution and those of a French multicentric study that included 131 patients. Preoperative patient selection and appropriate surgical technique, sometimes combined with preoperative portal embolization and local tumor destruction (radiofrequency and cryotherapy), may increase the resectability and the safety of the procedure. The mortality rate after hepatectomy was 0% (2.3% in the French study); the 3‐ and 6‐year survival rates were 91% and 68%, respectively, in our institution (the mean survival time was 66 months in the French multicentric survey). Significant prolonged survival with complete palliation of symptoms can be obtained after liver metastases resection with low mortality.
Subtotal Parathyroidectomy in Renal Failure: Still Needed after All These Years
Authors: Decker P. Anthony , Cohen Eric P. , Doffek Kara M. , Ashley Blake A. , Bienemann Mary E. , Zhu Yong Ran , Adams Mark E. , Wilson Stuart D. , Demeure Michael J.
Published: October 2003

There are scant data on the frequency of parathyroidectomy (PTX) for end‐stage renal disease (ESRD). Medical therapy for ESRD and secondary hyperparathyroidism has evolved to include better dialytic urea removal and the use of calcitriol. The aim of this study was to determine whether medical therapy has changed the frequency or indications for PTX in the management of renal failure. Hospital and clinic records were analyzed to gather information on all patients undergoing PTX for secondary hyperparathyroidism (2HPT) (n= 48) and tertiary hyperparathyroidism (3HPT) (n= 26) from 1986 through 1998 at our institution. Prospective computer databases were queried for information concerning both chronic dialysis and renal transplant patients at our center. The patients were divided based on date of operation before or after 1991, a divider that separated the patients into groups before or after the widespread adoption of intravenous calcitriol treatment during hemodialysis at our institution. Over the 12 year period, the proportion of our chronic dialysis patients undergoing PTX did not change significantly, ranging from 0% to 2.5% per year. Comparing all patients undergoing PTX for 2HPT during 1986–1991 versus 1992–1998, there was no significant difference in time on dialysis [7.0 ± 4.2 (n= 11) vs. 7.5 ± 4.6 (n= 36) years, mean ± SD]. The later group had higher intact parathyroid hormone (iPTH) levels [765 ± 415 (n= 6) vs. 1377 ± 636 (n= 28) pg/ml; p= 0.03], lower serum calcium [11.2 ± 1.0 (n= 12) vs. 9.9 ± 1.5 (n= 34) mg/dl; p= 0.006], and higher serum phosphate [5.7 ± 1.6 (n= 12) vs. 7.2 ± 2.3 (n= 31) mg/dl; p= 0.042]. Among the population of patients with transplants undergoing PTX for 3HPT, the average percent per year undergoing PTX ranged from 0% to 4.2% and did not change during the study period. Comparing the 1986–1991 group to the 1992–1998 group, the time from transplantation to PTX did not change during the study period (3.3 ± 2.3 vs. 2.9 ± 3.0 years; p= 0.391), and there were no significant differences between preoperative calcium levels or iPTH levels. Despite advances in dialysis technique and pharmacologic therapy, there has been no change in the proportion of dialysis patients requiring PTX for 2HPT or 3HPT. There was also no change in the time on dialysis for patients with 2HPT or the time from transplant to PTX for patients with 3HPT. Analysis of preoperative biochemical markers as evidence of disease severity suggests there was no change in indications for PTX during our study. From this information we conclude that parathyroid pathophysiology is incompletely understood and medical therapy is not optimal, resulting in a continuing need for PTX in some patients.
Importance of Early Screening and Prophylactic Thyroidectomy in Asymptomatic Nonindex RET Germline Carriers
Authors: Ukkat Jörg , Lorenz Kerstin , Hinze Raoul , Thomusch Oliver , Dralle Henning
Published: October 2003

Genetic testing for RET germline mutations affords rapid identification of germline carriers, offering the prospect of cure before C‐cell hyperplasia (CCH) has progressed to medullary thyroid carcinoma (MTC). Although nonindex RET mutation carriers have a better prognosis than do the index patients, it remains to be ascertained whether age represents a risk factor for MTC when screening patients. The current institutional study (October 1994 through June 1999) was set up to compare asymptomatic nonindex patients who were grouped by age: < 20 years and ≥ 20 years. Inclusion criteria were confirmed RET mutations in the germline, with no MTC being more advanced than pT1pN1M0. Adult patients (≥ 20 years) had MTC significantly more often (84% vs. 43%), significantly larger tumors (5 mm vs. 3 mm), and significantly higher basal calcitonin levels preoperatively (78.0 vs. 9.7 pg/ml) than their pediatric/adolescent counterparts (< 20 years). There was a close correlation between pT1 MTC and an elevated basal serum calcitonin level (r= 0.67; Spearman's rho). All three patients with lymph node metastases from MTC had elevated basal calcitonin levels. The two groups did not differ in terms of multifocality of MTC (pT1b), lymph node involvement (pN1) or bilateral lymph node metastasis (pN1b), or preoperative stimulated and postoperative basal and stimulated serum calcitonin. Prophylactic thyroidectomy should not be postponed beyond the age of 20, and it should be performed before basal serum calcitonin has turned positive. Pathologic conversion of stimulated serum calcitonin obviously marks the time in carriers of RET germline mutations when surgery should be scheduled at the latest to be prophylactic.
Merits and Demerits of Operative Procedure to the Trachea in Patients with Differentiated Thyroid Cancer
Authors: Nakao Kazuyasu , Kurozumi Kazushi , Fukushima Satsuki , Nakahara Masaaki , Tsujimoto Masahiko , Nishida Toshirou
Published: October 2003

Local radical thyroidectomy, including cervical lymph node dissection and combined circumferential resection of the trachea, has been performed over the past 20 years in 31 patients with differentiated cancer invading the trachea. The 5‐ and 10‐year survival rates for these patients were 77.4% and 66.7%, respectively. In 19 of the 31 (61%) cases the recurrent nerve was resected because of direct cancer invasion. Bilateral recurrent nerve palsy occurred in 12 patients, 3 of whom were managed postoperatively using a T‐shaped tube for preservation of the larynx. Hoarseness remained in 21 patients. In two patients with recurrent cancer invasion of the larynx, partial laryngectomy and hemilaryngectomy were performed, and reconstruction was done using ear cartilage without postoperative dyspnea or dysphagia. Parathyroid function is an important factor in regard to the quality of life of patients. In 22 patients at least one of the parathyroids was preserved. Postoperative calcium administration was necessary in 14 patients. Our long‐term observations indicate that local radical thyroidectomy with combined resection of the trachea can serve as a useful treatment for advanced differentiated cancer invading the airway.
Adrenocortical Carcinoma: Is Prognosis Different in Nonfunctioning Tumors? Results of Surgical Treatment in 31 Patients
Authors: Favia Gennaro , Lumachi Franco , D'Amico Davide F.
Published: October 2003

From 1980 to 1998 a series of 265 patients with adrenal tumors underwent surgery, with an adrenocortical carcinoma found in 31 (11.7%). Altogether, 17 (54.8%) patients (group A) had Cushing syndrome (n= 15) or virilization (n= 2), and 14 (45.2%) patients (group B) had nonfunctioning adrenal tumors. Tumor staging was as follows: (groups A/B): stage I, n= 5 (3/2), stage II, n= 14 (9/5), stage III, n= 5 (1/4), stage IV, n= 7 (4/3) patients. There were 12 (38.7%) men and 19 (61.3%) women (median age 51 years, range 25–73 years), and the size of the mass ranged from 3.5 to 20.0 cm (median 8.0 cm), with no differences (p= NS) between groups A and B. Two (6.4%) patients (stage IV) did not undergo surgery and received only palliative drug treatment; 6 (19.4%) were treated with debulking surgery; 15 (48.4%) had unilateral adrenalectomy; and 8 (25.8%) had an extended adrenalectomy. Eighteen (58.0%) patients underwent adjuvant postoperative mitotane treatment, and in 8 (25.8%) patients one or more reoperations for recurrence were required. Nine (29.0%) patients are still alive with a mean follow‐up of 34 months; 22 (71.0%) died 2 to 60 months (median 20 months) after surgery. The overall 2‐ and 5‐year survival rates were 62.1% and 10.3%, with no difference (p= NS) between groups A and B. The survival rates at the 1‐ and 3‐year follow‐ups were 90.3% and 32.3% (stages I and II) and 71.0% and 6.5% (stages III and IV). In conclusion, adrenocortical carcinoma remains a highly malignant tumor, and stage III–IV patients still have a poor prognosis; but nonfunctioning tumors do not seem to be more aggressive.
Cohort Study of Fever and Leukocytosis as Diagnostic and Prognostic Indicators in Infected Surgical Patients
Authors: Crabtree Traves D. , Pelletier Shawn J. , Antevil Jared L. , Gleason Thomas G. , Pruett Timothy L. , Sawyer Robert G.
Published: October 2003

The presence of fever and leukocytosis have traditionally been utilized as important diagnostic markers of infection despite some who question their reliability. To examine this point, the role of fever and leukocytosis as diagnostic and prognostic indicators for surgical infections was evaluated. A prospective observational study was performed on all patients with suspected infection in 1997 on the general surgical services at a university hospital. Fever was defined as maximum temperature (Tmax) ≥ 38.5°C, and leukocytosis was defined as a white blood cell (WBC) count ≥ 11,000/μl. Among all infections, patients presenting with a Tmax ≥ 38.5°C were younger (51.3 ± 1.1 vs. 53.8 ± 0.9 years, p= 0.005) and had a higher APACHE II score (15.1 ± 0.5 vs. 11.4 ± 0.4; p < 0.001). By logistic regression analysis chronic renal insufficiency was associated with a Tmax < 38.5°C [odds ratio (OR) 0.371, 95% confidence interval (CI) 0.195–0.704], and chronic steroid therapy was associated with a WBC count < 11,000/μl (OR 0.556, 95% CI 0.335–0.921). In addition, infected transplant patients were more likely to present with a Tmax < 38.5°C and a WBC count < 11,000/μl (OR 0.195, 95% CI 0.075–0.502). Mortality rates for infected patients with a Tmax < 38.5°C or > 38.5°C were 11.6% and 12.9%, respectively (p < 0.7), and the lengths of stay were 14 ± 1 and 18 ± 1 days, respectively (p < 0.03). Mortality rates for patients with a WBC count < 11,000/μl or > 11,000/μl were 4.7% and 18.6%, respectively (p < 0.001), and the lengths of stay were 14 ± 1 and 19 ± 1 days, respectively (p < 0.001). In the setting of infection, chronic renal insufficiency and chronic steroid therapy are associated with suppression of fever and leukocytosis, respectively. Transplantation is an independent predictor of infection in patients presenting without fever or leukocytosis. Leukocytosis, but not fever, may be predictive of hospital mortality in infected surgical patients.
Adrenal cortical carcinoma
Authors: Dackiw Alan P. B. , Lee Jeffrey E. , Gagel Robert F. , Evans Douglas B.
Published: October 2003

Adrenal cortical carcinoma is a rare endocrine tumor for which complete surgical resection is the only potentially curative treatment. Accurate preoperative evaluation (biochemical and radiographic) of the patient who presents with an adrenal mass maximizes the opportunity for the patient to undergo a complete, margin‐negative resection of the primary tumor, which is the most powerful prognostic variable for long‐term survival. The response to chemotherapy or mitotane is modest in patients with advanced disease. Hopefully, an improved understanding of the molecular pathogenesis of this challenging tumor will lead to the development of more effective therapies in the future.
Hyperparathyroidism in multiple endocrine neoplasia type I: Surgical trends and results of a 256‐patient series from groupe d’Etude des Néoplasies endocriniennes multiples study group
Authors: Goudet Pierre , Cougard Patrick , Vergès Bruno , Murat Arnaud , Carnaille Bruno , Calender Alain , Faivre Jean , Proye Charles
Published: October 2003

The French and Belgian GENEM study group’s multiple endocrine neoplasia type I (MEN‐I) database was used to evaluate trends in clinical presentation, surgical treatment of primary hyperparathyroidism (pHPT) (n=245), and prognostic factors for hypercalcemia correction among 256 MEN‐I cases. The patients were retrieved through the GENEM network from various Belgian and French instititutions with the help of genetics laboratories. Among the 245 pHPT patients (96%), 42% were men. The mean age at the time of diagnosis was 39.5 ± 13.3 years. Trends were studied for three periods: before 1986, from 1986 to 1990, and thereafter. After 1990 MEN‐I patients were more often diagnosed with isolated pHPT (8%, 11%, 28%, for the three periods, respectively; p=0.002); it was seen more often in screened patients (31%, 28%, 53%; p=0.001), more often among those in already known MEN‐I families (64%, 45%, 72%; p=0.005), and among those with lower preoperative calcemia (2.93, 2.87, 2.79 mmol/L; p=0.001). The age at pHPT diagnosis remained constant throughout the study. The percentage of cervical explorations dropped during the entire study (87%, 87%, 53%; p<0.0001). After 1985 the percentage of subtotal parathyroidectomies increased (25%, 59%, 51%; p=0.0004). Pathology disclosed more hyperplasias (59%, 85%, 74%; p=0.008). Postoperative hypercalcemia decreased (47%, 15%, 19%; p<0.0001); and postoperative hypocalcemia increased nonsignificantly (5%, 15%, 15%; p=0.1). Subtotal parathyroidectomy [odds ratio (OR) 13], no MEN‐I family background (OR 3), and the most recent study period (>1985) (OR 3) were significant predictive factors of hypercalcemia correction according to the multivariate analysis. This is the first multicentric study on the management of MEN‐I‐related pHPT. Immediate postoperative hHPT cure increased, but only 80% of the operated patients were cured after 1990. Fifteen percent were hypocalcemic. Because MEN‐I‐related hHPT cure remains difficult to achieve, we advocate that subtotal parathyroidectomies be performed in specialized centers.
Adrenocortical carcinomas: surgical trends and results of a 253‐patient series from the French Association of Endocrine Surgeons study group
Authors: Icard Philippe , Goudet Pierre , Charpenay Cyril , Andreassian Bernard , Carnaille Bruno , Chapuis Yves , Cougard Patrick , Henry Jean‐François , Proye Charles
Published: October 2003

Because of the rarity of adrenocortical carcinoma, survival rates and the prognosis for patients who have undergone operation are not well known. The purpose of the French Association of Endocrine Surgery was to evaluate these factors over an 18‐year period. A trend study was associated to assess changes in the clinical and biochemical presentations as well as the surgical evolution. A total of 253 patients (158 women, 95 men) with a mean age of 47 years were included. Cushing syndrome was the main clinical presentation (30%), and hormonal studies revealed secreting tumors in 66% of the cases. Altogether, 72% (n=182) of patients underwent resection for cure, and 41.5% (n=105) of them had an extensive resection because of metastatic cancer. A lymphadenectomy was performed in 32.5% (n=89) of the cases. The operative mortality was 5.5% (n=14). Patients were given mitotane as adjuvant therapy in 53.8% of the cases (n=135). The results of staging were stage I in 16 patients (6.3%), stage II (local disease) in 126 patients (49.8%), stage III (locoregional disease) in 57 patients (22.5%), and stage IV (metastases) in 54 patients (21.3%). Neither tumor staging nor the rate of curative surgery changed during the study period. More subcostal incisions were performed, and the use of mitotane increased significantly. The 5‐year actuarial survival rates were 38% overall, 50% in the curative group, 66% for stage I, 58% for stage II, 24% for stage III, and 0% for stage IV. Multivariate analysis showed that mitotane benefited only the group of patients not operated on for cure. A better prognosis was found in patients operated on after 1988 (p=0.04), in those with precursor‐secreting tumors (p=0.005), and in those at local stages of the disease (p=0.0003). Thus mitotane benefited only patients not operated on for cure. Curative resection, precursor secretion, recent diagnosis, and local stage were favorably associated with survival.
Indications for Early Postoperative Intraperitoneal Chemotherapy of Advanced Gastric Cancer: Results of a Prospective Randomized Trial
Authors: Yu Wansik , Whang Ilwoo , Chung Ho Young , Averbach Andrew , Sugarbaker Paul H.
Published: October 2003

Previous analysis of this prospective randomized trial and meta‐analysis of published randomized trials of adjuvant intraperitoneal chemotherapy demonstrated improved survival in patients with advanced gastric cancer. Simple criteria applicable at the time of surgery for patient selection were sought in this analysis. From 1990 to 1995 a series of 248 patients with biopsy‐proven gastric cancer were randomized intraoperatively to receive early postoperative intraperitoneal mitomycin C and 5‐fluorouracil (125 patients) versus surgery only (123 patients). Gastric resection plus early postoperative intraperitoneal chemotherapy showed improved overall survival compared to surgery only (54% and 38%, respectively; p= 0.0278). There were statistically significant differences in patients with stage III (57% and 23%, respectively; p= 0.0024) and in those with stage IV (28% and 5%, respectively; p= 0.0098) gastric cancer. The improvement in survival rate was statistically significant for the subgroup of patients with gross serosal invasion (52% and 25%, respectively; p= 0.0004) and patients with lymph node metastasis (46% and 22%, respectively; p= 0.0027). The surgeons' impression about lymph node status was unreliable, but assessment of serosal invasion was accurate in 80% of cases. Gross serosal invasion with or without frozen section evaluation of lymph nodes can be used as the major selection criteria for early postoperative intraperitoneal chemotherapy of advanced gastric cancer.
Characteristics of Multicentric Hepatocellular Carcinomas: Comparison with Intrahepatic Metastasis
Authors: Shimada Mitsuo , Hamatsu Takayuki , Yamashita Yo‐ich , Rikimaru Tatsuya , Taguchi Ken‐ichi , Utsunomiya Tohru , Shirabe Ken , Sugimachi Keizo
Published: October 2003

Characteristics of multicentric hepatocellular carcinomas (HCCs) remain obscure. We therefore aimed to clarify them and compare them with HCC with intrahepatic metastases. A series of 118 patients who had definite hepatitis C viral status and multinodular HCC were divided into two groups: a multicentric occurrence (MO) group (n= 38), with multicentric HCCs; and an intrahepatic metastasis (IM) group (n= 80), with HCC having intrahepatic metastases. Clinicopathologic variables, including the patient's survival and disease‐free survival rates, were compared between the MO and IM groups. Univariate analysis revealed the presence of esophageal varices, the presence of hepatitis C virus infection, a platelet count of less than 10 × 104/μl, hepaplastin test, γ‐globulin, the histologically active hepatitis, tumor size, des‐γ‐carboxy prothrombin > 0.1 AU/ml, positive portal vein invasion, and histologic grade as discriminating factors. The MO score to differentiate multicentric HCCs from intrahepatic metastatic HCCs was determined using the following four independent factors selected by a stepwise regression analysis: the presence of hepatitis C virus infection, a platelet count of less than 10 × 104/μl, tumor size, and histologic grade. The sensitivity and specificity of the MO scores using those factors were 84% and 70%, respectively, when the cutoff value was 0.4. The disease‐free survival rate in the MO group was similar to that in the IM group, whereas the survival rate in the MO group was significantly better than that in the IM group. The multivariate analysis revealed the multicentric occurrence of HCC as one of the independent prognostic factors. Clinicopathologic factors differentiating multicentric HCCs from intrahepatic metastatic HCCs were the presence of hepatitis C virus infection, a platelet count of less than 10 × 104/μl, small tumor size, and low histologic grade.