bluuebunny/crossref_metadata_2025 huggingface dataset:
Directed graphs, Hamiltonicity and doubly stochastic matrices
Authors: Borkar Vivek S. , Ejov Vladimir , Filar Jerzy A.
Published: August 2004

We consider the Hamiltonian cycle problem embedded in singularly perturbed (controlled) Markov chains. We also consider a functional on the space of stationary policies of the process that consists of the (1,1)‐entry of the fundamental matrices of the Markov chains induced by the same policies. In particular, we focus on the subset of these policies that induce doubly stochastic probability transition matrices, which we refer to as the “doubly stochastic policies.” We show that when the perturbation parameter ϵ is sufficiently small the minimum of this functional over the space of the doubly stochastic policies is attained very close to a Hamiltonian cycle, provided that the graph is Hamiltonian. We also derive precise analytical expressions for the elements of the fundamental matrix that lend themselves to probabilistic interpretation as well as asymptotic expressions for the first diagonal element, for a variety of deterministic policies that are of special interest, including those that correspond to Hamiltonian cycles. © 2004 Wiley Periodicals, Inc. Random Struct. Alg., 2004
Burnout, stress and health of employees on non‐standard work schedules: a study of Canadian workers
Authors: Jamal Muhammed
Published: August 2004

This study examined the relationship between non‐standard work schedules (shift work and weekend work) and job burnout, stress and psychosomatic health problems among full‐time employed Canadians in a large metropolitan city on the east coast. Data were collected by means of a structured mail back questionnaire (N = 376). Employees involved with weekend work reported significantly higher emotional exhaustion, job stress and psychosomatic health problems than employees not involved with weekend work. Similarly, employees on non‐standard work shifts (other than fixed day shift, 9 a.m.–5 p.m.) reported significantly higher overall burnout, emotional exhaustion, job stress and health problems than employees on a fixed day shift. Results from two‐way ANOVA indicated that employees involved with weekend work and non‐fixed day shifts reported significantly higher emotional exhaustion and health problems than other employees. Implications of the findings are discussed for future researchers in light of employee well‐being and non‐standard work schedules. Copyright © 2004 John Wiley & Sons, Ltd.
Using consumer demands to bridge the gap between software engineering and usability engineering
Authors: Scholtz Jean , Morse Emile
Published: August 2004

A number of efforts are being undertaken to integrate usability engineering and software engineering in the software‐development process. The majority of these integration efforts focus on software developers, usability engineers, or defining new processes. In this article, we report on an effort to involve the consumer of software by providing a mechanism, namely the common industry format (CIF), to formally request usability information on the software to be purchased. Copyright © 2004 John Wiley & Sons, Ltd.
The usability design process – integrating user‐centered systems design in the software development process
Authors: Göransson Bengt , Gulliksen Jan , Boivie Inger
Published: August 2004

This article reviews current efforts in bridging the gaps between software engineering and Human–Computer Interaction (HCI) and describes some critical issues that must be resolved in order to reconcile some of the differences between the two fields. We argue that user‐centered systems design (UCSD) must be tightly integrated in the software development process and suggest the usability design process as a way of doing this. The usability design process is a UCSD approach for developing usable interactive systems, combining usability engineering with interaction design, and emphasizing extensive active user involvement throughout the iterative process. We outline the usability design process and illustrate the steps in the process with examples from real‐life design cases. Finally, we provide an example of how the usability design process can be implemented in a commercial software‐development process, Rational Unified Process™ (RUP). Copyright © 2004 John Wiley & Sons, Ltd.
Long‐term prenatal hypoxia alters maturation of brain catecholaminergic systems and motor behavior in rats
Authors: Perrin David , Mamet Julie , Scarna Hélène , Roux Jean Christophe , Bérod Anne , Dalmaz Yvette
Published: August 2004

In order to determine the influence of long‐term prenatal hypoxia on the maturation of the brain catecholaminergic structures involved in motor and cognitive functions, pregnant rats were subjected to hypoxia (10% O2) from the 5th to 20th day of gestation. The in vivo activity of tyrosine hydroxylase (TH), the rate‐limiting enzyme in catecholamine biosynthesis, was assessed, by accumulation of L‐DOPA after i.p. administration of NSD‐1015, in the motor cortex areas, the hippocampus, and the striatum at birth and at the 3rd, 7th, 14th, 21st, and 68th postnatal days. The motor reactivity to novelty and the circadian motor activity were measured at the 21st and 68th postnatal days. Exposure to prenatal hypoxia strongly altered the developmental pattern of in vivo TH activity in restricted noradrenergic terminals of the brain. In the 21‐day‐old prenatal hypoxic rats, the TH activity was reduced by 80% in the motor cortex areas and by 43% in the hippocampus, compared to control rats, while no differences could be detected in the striatum. Compared to control rats, the prenatal hypoxic pups exhibited a higher motor reactivity to novelty and a nocturnal motor hypoactivity at the 21st postnatal day. The neurochemical and behavioral alterations were no longer observed at the 68th postnatal day. The altered in vivo TH activity in the young rats might be part of the neural mechanisms contributing to the motor behavioral impairments induced by prenatal hypoxia. Long‐term prenatal hypoxia could be linked to the development of psychopathologies that can be detected in infancy. Synapse 54:92–101, 2004. © 2004 Wiley‐Liss, Inc.
Binding characteristics of high‐affinity dopamine D2/D3 receptor agonists, 11C‐PPHT and 11C‐ZYY‐339 in rodents and imaging in non‐human primates by PET
Authors: Mukherjee Jogeshwar , Narayanan Tanjore K. , Christian Bradley T. , Shi Bingzhi , Yang Zhi‐Ying
Published: August 2004

We have evaluated the in vitro autoradiographic binding characteristics and in vivo brain distribution of two high‐affinity dopamine D2/D3 receptor agonists, (±)‐2‐(N‐phenethyl‐N‐1′‐11C‐propyl)amino‐5‐hydroxytetralin (11C‐PPHT) and (±)‐2‐(N‐cyclohexylethyl‐N‐1′‐11C‐propyl)amino‐5‐hydroxytetralin (11C‐ZYY‐339) in rodents and in monkeys using positron emission tomography (PET). In vitro autoradiograms in rat brain slices with 11C‐PPHT and 11C‐ZYY‐339 revealed binding to dopaminergic regions in the striata, which was substantially (>90%) displaced by 10 μM sulpiride. Striatal binding was also removed in the presence of 5‐guanylylimidophosphate (Gpp(NH)p), indicative of binding of these radiotracers to the high‐affinity (HA) state. The results of in vivo studies in rats exhibited binding of the two radiotracers to the striata (striata/cerebellum approached 2 in 30 min). The regional selectivity to the striata was reduced by preadministration of haloperidol. PET studies in male rhesus monkeys using an ECAT EXACT HR+ scanner indicated localization of 11C‐PPHT and 11C‐ZYY‐339 in the striata and thalamus. Striata to cerebellum and thalamus to cerebellum ratios were low (1.5 and 1.3, respectively, at 30 min postinjection) for both 11C‐PPHT and 11C‐ZYY‐339, apparently due to the slower nonspecific clearance from cerebellum. These findings with 11C‐PPHT and 11C‐ZYY‐339 indicate the possibility of in vivo imaging of high‐affinity state of dopamine D2/D3 receptors in both the striata and the thalamus. Synapse 54:83–91, 2004. © 2004 Wiley‐Liss, Inc.
Reasoning from data: How students collect and interpret data in science investigations
Authors: Kanari Zoe , Millar Robin
Published: August 2004

This study explored the understandings of data and measurement that school students draw upon, and the ways that they reason from data, when carrying out a practical science inquiry task. The two practical tasks used in the study each involved investigations of the relationships between two independent variables (IVs) and a dependent variable (DV); in both tasks, one IV covaried with the DV, whereas the other did not. Each was undertaken by 10 students, aged 10, 12, and 14 years (total n = 60 students), working individually. Their actions were video‐recorded for analysis. In a subsequent interview, each student was asked to discuss and interpret data collected by two other students, undertaking a similar (but different) practical task, shown on a video‐recording. An analysis of the sample students' performance on the practical tasks and their interview responses showed few differences across task contexts, or with age, in students' reasoning, but significant differences in performance when investigating situations of covariation and non‐covariation. Few students in the sample displayed sufficient understanding of measurement error to deal effectively with the latter. Investigations of non‐covariation cases revealed, much more clearly than investigations of covariation cases, the students' ideas about data and measurement, and their ways of reasoning from data. Such investigations therefore provide particularly valuable contexts for teaching and research. © 2004 Wiley Periodicals, Inc. J Res Sci Teach 41: 748–769, 2004
Environmental isolation of Cryptococcus neoformans from an endemic region of HIV‐associated cryptococcosis in Thailand
Authors: Kuroki Misuzu , Phichaichumpon Cheseda , Yasuoka Akira , Chiranairadul Piphat , Chosa Toru , Sirinirund Petchsri , Miyazaki Taiga , Kakeya Hiroshi , Higashiyama Yasuhito , Miyazaki Yoshitsugu , Ishida Yutaka , Kohno Shigeru
Published: August 2004

We successfully isolated Cryptococcus neoformans from chicken faeces in suburban areas of Thailand. C. neoformans was isolated from 36/150 houses (24.0%) in the dry season and 6/150 (4.0%) in the rainy season. All environmental isolates were of serotype A. The high isolation rate of 24% from chicken faeces has never been reported previously. Our environmental study could probably explain the high incidence of cryptococcal meningitis in HIV patients in Thailand. Copyright © 2004 John Wiley & Sons, Ltd.
Characterization of Kluyveromyces lactis subtelomeric sequences including a distal element with strong purine/pyrimidine strand bias
Authors: Nickles Kristy , McEachern Michael J.
Published: August 2004

Telomeres are the specialized structures at the ends of eukaryotic chromosomes and are composed of short T/G‐rich DNA repeats and the proteins that interact with them. Internal to telomeres are subtelomeric regions that are species‐specific and often repetitive. The yeast Kluyveromyces lactis has telomeric tracts of 10–20 copies of a 25 bp repeat, but the subtelomeric regions have not previously been characterized in detail. Here we have cloned and characterized subtelomeric regions from 10 of the 12 chromosome ends. The amount of sequence examined was 0.7–10 kb for each subtelomeric region. We have identified a K. lactis subtelomeric element, the R element, which has a strong purine/pyrimidine strand bias and extends for about 2 kb. Internal to the R element, we found extensive similarity that is shared among half of the chromosome ends reported here. This similarity appears to include three putative gene families, two of which are also subtelomeric in Saccharomyces cerevisiae. GenBank Accession Nos: P1, AY437818; P2, AY437819; P3, AY437820; P4, AY437821; P5, AY437822; P6, AY437823; P7‐5′, AY437824; P7‐3′, AY437825; P9‐5′, AY437826; P9‐3′, AY437827; P10, AY437828; P11‐5′, AY437829; P11‐3′, AY437830. Copyright © 2004 John Wiley & Sons, Ltd.
Modelling the dynamics of the yeast pheromone pathway
Authors: Kofahl Bente , Klipp Edda
Published: August 2004

We present a mathematical model of the dynamics of the pheromone pathways in haploid yeast cells of mating type MATa after stimulation with pheromone α‐factor. The model consists of a set of differential equations and describes the dynamics of signal transduction from the receptor via several steps, including a G protein and a scaffold MAP kinase cascade, up to changes in the gene expression after pheromone stimulation in terms of biochemical changes (complex formations, phosphorylations, etc.). The parameters entering the models have been taken from the literature or adapted to observed time courses or behaviour. Using this model we can follow the time course of the various complex formation processes and of the phosphorylation states of the proteins involved. Furthermore, we can explain the phenotype of more than a dozen well‐characterized mutants and also the graded response of yeast cells to varying concentrations of the stimulating pheromone. Copyright © 2004 John Wiley & Sons, Ltd.
Role of the N‐terminal region of Rap1p in the transcriptional activation of glycolytic genes in Saccharomyces cerevisiae
Authors: Mizuno Takayuki , Kishimoto Tomoko , Shinzato Tomoko , Haw Robin , Chambers Alistair , Wood Jason , Sinclair David , Uemura Hiroshi
Published: August 2004

In the yeast two‐hybrid system, the N‐terminal region of Rap1p was shown to interact with Gcr1p and Gcr2p. Disruption of gcr1 and/or gcr2 in the two‐hybrid reporter strain demonstrated that the interaction with Gcr1p does not require Gcr2p, whereas the interaction with Gcr2p is mediated through Gcr1p. Deletion of the N‐terminal region of Rap1p alone did not show a growth phenotype, but a growth defect was observed when this mutation was combined with a gcr2 deletion. The poor growth of the gcr1 null mutant was not affected further by the N‐terminal deletion of Rap1p, but the growth of gcr1 strains with mutations in the DNA binding region of Gcr1p was affected by the removal of the N‐terminal region of Rap1p. These results suggest that one function of the N‐terminal region of Rap1p, presumably the BRCT domain, is to facilitate the binding of Gcr1p to the promoter by a protein–protein interaction. Copyright © 2004 John Wiley & Sons, Ltd.
Characterization of end4+, a gene required for endocytosis in Schizosaccharomyces pombe
Authors: Iwaki Tomoko , Tanaka Naotaka , Takagi Hiroshi , Giga‐Hama Yuko , Takegawa Kaoru
Published: August 2004

To understand endocytic trafficking in Schizosaccharomyces pombe, we constructed an end4 disruption mutant. The end4+ gene encodes a protein homologous to Sla2p/End4p, which is essential for the assembly and function of the cytoskeleton and endocytosis in Saccharomyces cerevisiae. We characterized the fission yeast mutant end4Δ as well as ypt7Δ, which is deficient in vacuolar fusion and, hence, endocytosis. The delivery of FM4‐64 to the vacuolar membrane, accumulation of Lucifer yellow CH and internalization of plasma membrane protein Map3–GFP were inhibited in the end4 mutant. Deletion of end4 resulted in pleiotropic phenotypes consistent with F‐actin depolarization, including high temperature sensitivity, abnormal morphology and mating defects. Extensive missorting of carboxypeptidase Y was detected in the ypt7 mutant; however, little missorting was detected in the end4 mutant. These results indicate that End4p is essential for the internalization process and Ypt7p affects endocytosis at a post‐internalization step after the intersection of the endocytic and the vacuolar protein‐sorting pathways in fission yeast. Copyright © 2004 John Wiley & Sons, Ltd.
Characterization of Candida albicans orthologue of the Saccharomyces cerevisiae signal‐peptidase‐subunit encoding gene SPC3
Authors: De la Rosa José M. , González José M. , Gutiérrez Fernando , Ruíz Teresa , Rodríguez Luis
Published: August 2004

The Candida albicans orthologue of the SPC3 gene, which encodes one of the subunits essential for the activity of the signal peptidase complex in Saccharomyces cerevisiae, was isolated by complementation of a thermosensitive mutation in the S. cerevisiae SEC61 gene. The cloned gene (CaSPC3) encodes a putative protein of 192 amino acids that contains one potential membrane‐spanning region and shares significant homology with the corresponding products from mammalian (Spc22/23p) and yeast (Spc3p) cells. CaSPC3 is essential for cell viability, since a hemizygous strain containing a single copy of CaSPC3 under control of the methionine‐repressible MET3 promoter did not grow in the presence of methionine and cysteine. The cloned gene could rescue the phenotype associated with a spc3 mutation in S. cerevisiae, indicating that it is the true C. albicans orthologue of SPC3. However, in contrast with results previously described for its S. cerevisiae orthologue, CaSPC3 was not able to complement the thermosensitive growth associated with a mutation in the SEC11 gene. The heterologous complementation of the sec61 mutant suggests that Spc3p could play a role in the interaction that it is known to occur between the translocon (Sec61 complex) and the signal peptidase complex, at the endoplasmic reticulum membrane. Copyright © 2004 John Wiley & Sons, Ltd.
Novel Operative Technique for Vagal Nerve‐ and Pyloric Sphincter‐preserving Distal Gastrectomy Reconstructed by Interposition of a 5 cm Jejunal J Pouch with a 3 cm Jejunal Conduit for Early Gastric Cancer and Postoperative Quality of Life 5 Years after Operation
Authors: Tomita Ryouichi , Tanjoh Katsuhisa , Fujisaki Shigeru
Published: August 2004

The importance of the vagal nerve and pyloric sphincter, the need for pouch reconstruction, and the ideal pouch volume are all matters of controversy. A novel operative technique for vagal nerve‐ and pyloric sphincter‐preserving distal gastrectomy reconstructed by interposition of a 5 cm jejunal J pouch with a 3 cm jejunal conduit was developed as a function‐preserving surgical technique to prevent postgastrectomy disorders. The application criteria and technique are outlined in this article. Postoperative quality of life was also investigated clinically. Twenty subjects who underwent this surgical operation (group A: 16 men and 4 women aged 41 to 70 years, mean age 59.5 years) were interviewed to inquire about postoperative gastrointestinal symptoms. These patients were compared with 44 others who underwent conventional distal gastrectomy with D2 lymphadenectomy (group B: 30 men and 14 women aged 43 to 73 years, mean age 62.6 years). Included were patients with early cancer [mucosal or submucosal 1 (SM1) cancer and no lymph node metastasis (N0)] in the middle or lower third of stomach (or both) who were either not eligible for endoscopic excision of gastric mucosa or for partial gastric excision in the mucosa = 3.5 cm or SM1 5.5 cm, or further in distance from the anal margin of the cancer to the pyloric sphincter. Cases in which the remnant stomach would become one‐third or less of the original size were also applied. During excision with lymph nodes, the hepatic and celiac branches bifurcating from the anterior and posterior trunks of the vagal nerve were preserved. The antrum was severed 1.5 cm from the pyloric sphincter, preserving the arteria supraduodenalis. The substitute stomach was created as a 5 cm jejunal pouch with a 3 cm jejunal conduit for orthodromic peristaltic movement using an automatic suture instrument to complete a side‐to‐side anastomosis of the folded jejunum. The anal side of the gastric remnant was manually anastomosed with the jejunal J pouch, and anastomosis of the pyloric antrum with the jejunal conduit was manually completed by stratum anastomosis. Postoperatively, the procedure in group A alleviated gastrointestinal symptoms such as appetite loss, epigastric fullness, reflux esophagitis, early dumping syndrome, body weight loss, endoscopic reflux esophagitis, and endoscopic gastritis in the remnant stomach, postprandial stasis of the substitute stomach, and postgastrectomy cholecystolithiasis better than in group B. The results suggest that the proposed technique is a function‐preserving gastric operation appropriate for preventing postgastrectomy disorder.
Desmoplastic Reaction Influences Pancreatic Cancer Growth Behavior
Authors: Hartel Mark , di Mola Fabio F. , Gardini Andrea , Zimmermann Arthur , Di Sebastiano Pierluigi , Guweidhi Ahmed , Innocenti Paolo , Giese Thomas , Giese Nathalia , Büchler Markus W. , Friess Helmut
Published: August 2004

Connective tissue growth factor (CTGF), which is regulated by transforming growth factor‐ß (TGFß), has recently been implicated in the pathogenesis of fibrotic diseases and tumor stroma. Inasmuch as generation of desmoplastic tissue is characteristic for pancreatic cancer, it is not known whether it gives pancreatic cancer cells a growth advantage or is a reaction of the body to inhibit cancer cell progression. In the present study we analyzed the expression and localization of CTGF and evaluated whether it influences the prognosis of pancreas cancer. Tissue samples were obtained from 25 individuals (6 women, 19 men) undergoing pancreatic resection for pancreatic cancer. Tissue samples from 13 previously healthy organ donors (5 women, 8 men) served as controls. Expression of CTGF was studied by Northern blot analysis. In situ hybridization and immunohistochemistry localized the respective mRNA moieties and proteins in the tissue samples. Northern blot analysis revealed that pancreatic cancer tissue samples exhibited a 46‐fold increase in CTGF mRNA expression (p < 0.001) over that of normal controls. In vitro studies confirmed that pancreatic stellate cells are the major source of CTGF mRNA expression and revealed a large variance in basal and TGFß‐induced CTGF expression in cultured pancreatic cancer cells. This could also be confirmed by in situ hybridization, indicating that CTGF mRNA signals were located principally in fibroblasts, with only weak signals in the cancer cells. High CTGF mRNA levels in the tissue samples correlated with better tumor differentiation (p < 0.03). In addition, patients whose tumors exhibited high CTGF mRNA levels (> onefold increase above normal controls) lived significantly longer than those whose tumors expressed low CTGF mRNA levels (none to onefold) (p < 0.04 multivariate analysis). Our present data indicate that CTGF, as a downstream mediator of TGFß, is overexpressed in connective tissue cells and to a lesser extent in pancreatic cancer cells. Because patients with high CTGF mRNA expression levels have a better prognosis, our findings indicate that the desmoplastic reaction provides a growth disadvantage for pancreatic cancer cells.
Dependence of Positive Effects of Granulocyte Colony‐stimulating Factor on the Antibiotic Regimen: Evaluation in Rats with Polymicrobial Peritonitis
Authors: Bauhofer Artur , Torossian Alexander , Lorenz Wilfried , Middeke Martin , Plaul Ulrike , Schütz Philipp , Stinner Benno , Hattel Markus , Celik Ilhan ,   Lucerne Sepsis Study Group
Published: August 2004

We tested the hypothesis that the ability of granulocyte colony‐stimulating factor (G‐CSF) to prevent death from fecal peritonitis is influenced by the composition of the antibiotic regimen with which it is administered. We used a rodent model of polymicrobial peritoneal contamination and infection and the concept of clinical modeling randomized trials (CMRTs), which includes the conditions of randomized, clinical trials and complex clinical interventions (e.g., anesthesia, volume substitution, antibiotics, surgery, postoperative analgesia). With the peritonitis model we obtained a mortality dose‐response curve that was sensitive to antibiotic prophylaxis. G‐CSF was most efficacious when it was administered both prophylactically and after the onset of peritonitis. Cefuroxime/metronidazole, ofloxacin/metronidazole, and amoxicillin/clavulanate improved survival in combination with G‐CSF best, whereas cefotaxime or ceftriaxone with and without metronidazole did not. G‐CSF administration was associated with improved polymorphonuclear neutrophil phagocytosis and enhanced bacterial clearance. Pro‐inflammatory cytokine release (tumor necrosis factor‐a, interleukin‐6, macrophage inflammatory protein‐2) was decreased in plasma and in the peritoneal fluid. Their expression was lowered in various organs on the protein and mRNA level. The results were used to design a clinical trial to test the ability of G‐CSF to prevent serious infections in patients with colorectal cancer surgery. In this trial G‐CSF application and antibiotic prophylaxis were performed with the most effective scheduling and combinations (cefuroxime/metronidazole and ofloxacin/metronidazole) as defined here.
Prognostic Impact of Fas Ligand on Hepatocellular Carcinoma after Hepatectomy
Authors: Lee Wei‐Chen , Yu Ming‐Chin , Chen Miin‐Fu
Published: August 2004

The expression of Fas ligand on tumor cells may counterattack the host’s immunity and worsen the prognosis. Knowledge of the prognostic impact of Fas ligand on patients with hepatocellular carcinoma (HCC) after hepatectomy is still limited. Fas ligand expression in HCCs was examined in 59 patients who underwent hepatectomy for HCC. The prognosis was analyzed and correlated to the expression of Fas ligand. Expression of Fas ligand was detected by immunohistochemical staining in 27 of the 59 HCCs (45.8%). The Fas ligand was expressed in only a small number of cancer cells. However, even though only a few cancer cells expressed it, the prognosis for patients whose HCCs showed Fas ligand expression was worse than that for patients with an HCC without Fas ligand expression. The mean disease‐free survival was only 10.83 ± 1.90 months when HCCs expressed Fas ligand compared with 43.51 ± 7.02 months for those without Fas ligand expression (p = 0.0007). The overall patient survival was 28.34 ± 4.08 months when the HCC expressed Fas ligand compared with 55.31 ± 5.37 months for HCC without Fas ligand expression (p = 0.0003). The expression of Fas ligand did not correlate with the presentation of other prognostic factors. Fas ligand expression is thus an independent prognostic factor for HCC. Thus the HCC expressing Fas ligand has a worse prognosis than the HCC without Fas ligand expression.
Pleurodesis in Patients with Malignant Pleural Effusions: Talc Slurry or Bleomycin? Results of a Prospective Randomized Trial
Authors: Haddad Fabio José , Younes Riad Naim , Gross Jefferson Luiz , Deheinzelin Daniel
Published: August 2004

The purpose of this study was to evaluate the efficacy, safety, and cost of bedside pleurodesis for malignant pleural effusions using talc slurry (TS) or bleomycin (BL) in a prospective randomized trial, and to determine prognosticators for procedure failure. From June 1997 to June 1999 a series of 71 patients entered this trial. They underwent 37 procedures with TS (4 g) and 34 with BL (60 units) via tube thoracostomy. Success was defined as no recurrence of pleural effusion or asymptomatic recurrence of a small amount of effusion. Pleural effusion‐free survival curves were used to analyze the success rates and the prognosticators of failure. Follow‐up ranged from 3 days to 26 months (median 2.5 months). No difference in success rates was detected between TS or BL (log‐rank test: p = 0.724). There were no major complications related to the procedure. The independent prognosticators of failed pleurodesis were the use of steroids (p = 0.004) and the volume of pleural fluid drained during the first thoracentesis when it was more than 900 ml (p = 0.029). The average cost of intervention per patient was significantly lower for TS (p < 0.001). There was no significant difference between the success rates for TS and BL as agents of bedside pleurodesis for malignant pleural effusions. Because of its significantly lower cost, TS should be considered the agent of choice. The use of steroids and the volume drained during the first thoracentesis (if more than 900 ml) were independent prognosticators of pleurodesis failure. The role of this latter finding as a marker of pleurodesis failure awaits more data.
Cell‐specific Cytotoxicity of Human Pancreatic Adenocarcinoma Cells Using Rat Insulin Promoter Thymidine Kinase‐directed Gene Therapy
Authors: Tirone Thomas A. , Wang Xaio‐Ping , Templeton Nancy S. , Lee Tim , Nguyen Liz , Fisher William , Brunicardi F. Charles
Published: August 2004

The formation of a normal pancreas and the activation of insulin production are, in part, dependent on the expression and activation of the pancreatic duodenal homeobox gene 1 (PDX‐1). The expression of PDX‐1 also has been detected in various human pancreatic ductal adenocarcinoma (PDA) cell lines. This has made it possible to generate a cancer cell‐specific gene expression system to treat human pancreatic cancer. In this study, we have developed a cell‐specific cytotoxic model of PDA cells using the expression of herpes simplex virus thymidine kinase (TK) under the control of the rat insulin promoter (RIP‐TK). We have shown that the cell‐specific cytotoxicity in human PDA cells depends on the presence of PDX‐1. Our results also demonstrate that in vivo PDA‐specific cytotoxicity can be achieved with RIP‐TK using an intraperitoneal liposomal gene delivery method followed by a short period of ganciclovir treatment in severe combined immunodeficient (SCID) mice. Furthermore, PDX‐1 protein was found in all six freshly isolated human pancreas cancer specimens and two liver metastasis samples that were group‐tested, suggesting the feasibility of using RIP‐TK gene therapy in humans. This study may provide an alternative strategy for the future treatment of pancreatic cancer.
Venous Thromboembolism Prophylaxis after Head and Spinal Trauma: Intermittent Pneumatic Compression Devices Versus Low Molecular Weight Heparin
Authors: Kurtoglu Mehmet , Yanar Hakan , Bilsel Yilmaz , Guloglu Recep , Kizilirmak Sevda , Buyukkurt Dincay , Granit Volkan
Published: August 2004

Although there are alternative methods and drugs for preventing venous thromboembolism (VTE), it is not clear which modality is most suitable and efficacious for patients with severe (stable or unstable) head/spinal injures. The aim of this study was to compare intermittent pneumatic compression devices (IPC) with low‐molecular‐weight heparin (LMWH) for preventing VTE. We prospectively randomized 120 head/spinal traumatized patients for comparison of IPC with LMWH as a prophylaxis modality against VTE. Venous duplex color‐flow Doppler sonography of the lower extremities was performed each week of hospitalization and 1 week after discharge. When there was a suspicion of pulmonary embolism (PE), patients were evaluated with spiral computed tomography. Patients were analyzed for demographic features, injury severity scores, associated injuries, type of head/spinal trauma, complications, transfusion, and incidence of deep venous thrombosis (DVT) and PE. Two patients (3.33%) from the IPC group and 4 patients (6.66%) from the LMWH group died, with their deaths due to PE. Nine other patients also succumbed, unrelated to PE. DVT developed in 4 patients (6.66%) in the IPC group and in 3 patients (5%) in the LMWH group. There was no statistically significant difference regarding a reduction in DVT, PE, or mortality between groups (p = 0.04, p > 0.05, p > 0.05, respectively). IPC can be used safely for prophylaxis of VTE in head/spinal trauma patients.
Long‐term Results of Through‐knee Amputation with Dorsal Musculocutaneous Flap in Patients with End‐stage Arterial Occlusive Disease
Authors: Kock Hans‐Juergen , Friederichs Jan , Ouchmaev Alexander , Hillmeier Joachim , von Gumppenberg Stephan
Published: August 2004

A modified technique of knee joint disarticulation using a dorsal musculocutaneous flap of the gastrocnemius muscle was first described in 1985. The operative results in 66 patients (33 women, 33 men; mean age 66.7 ± 11.3 years, range 42–93 years) with gangrene due to peripheral vascular disease with 69 knee disarticulations are reported. After a mean survival period of 35.2 months (0–116 months), 88% (n = 58) of the patients had died owing to cardiopulmonary reasons. The in‐hospital 48‐day mortality was 9%. Nine patients (14%) underwent reamputation at the above‐knee level, and five patients underwent operative revision of the soft tissue. After discharge from the hospital, 35 of 60 patients (58%) were able to walk with the aid of a prosthesis. We conclude that knee disarticulation with the use of a myocutaneous gastrocnemius flap is a safe, functionally acceptable operative method in high risk vascular patients.
Factors Predicting Malignancy of Hürthle Cell Tumors of the Thyroid: Influence on Surgical Treatment
Authors: Pisanu Adolfo , Sias Luigi , Uccheddu Alessandro
Published: August 2004

Controversy still exists about the ability to differentiate between malignant and benign Hürthle cell tumors (HCTs) before and during surgery. Diagnostic difficulties make surgical decisions debatable. The aim of this study was to evaluate factors predicting the malignancy of HCT and to plan its appropriate management. From January 1998 to May 2003 a series of 41 patients underwent thyroidectomy in our surgical department because of HCT. A cross‐sectional study of 23 patients with carcinoma and 18 patients with adenoma was carried out: demographic data, tumor characteristics, diagnostic results of fine‐needle aspiration cytology (FNAC), frozen section (FS), MIBI scan scintigraphy, surgical indications, and treatment were evaluated. The mean tumor size was significantly greater for carcinomas than adenomas (3.1 vs. 1.9 cm; p = 0.006). Threshold sizes of more than 3.0 cm and 4.0 cm, respectively, were significant for predicting malignancy (p = 0.025 and p = 0.012). Conversely, 47.8% of carcinomas had a diameter smaller than 3.0 cm. FNAC and FS sensitivities for carcinoma detection were 23.8% and 33.3%, respectively. The positive uptake on MIBI scan imaging was likely to be similarly malignant or benign. Because of the lack of accuracy of all diagnostic studies for predicting malignancy, all oxyphilic cell nodules should be referred to surgery. Different tumor sizes cannot be the only factor on which to base a surgical decision. Therefore, because of diagnostic uncertainties, we believe that an experienced surgeon can safely perform total thyroidectomy in all patients with an HCT.
Hepatitis C Virus Infection is a Risk Factor for Tumor Recurrence after Resection of Small Hepatocellular Carcinomas
Authors: Huo Teh‐Ia , Wu Jaw‐Ching , Hsia Cheng‐Yuan , Chau Gar‐Yang , Lui Wing‐Yiu , Huang Yi‐Hsiang , Lee Pui‐Ching , Chang Full‐Young , Lee Shou‐Dong
Published: August 2004

Hepatocellular carcinoma (HCC) is closely associated with chronic hepatitis B or C virus (HBV, HCV) infection. Tumor recurrence frequently occurs after surgical resection and may adversely affect the outcome. This study aimed to investigate the effect of viral hepatitis in association with HCC recurrence after resection. A total of 248 patients [HBV in 165, HCV in 44, dual HBV+HCV in 15, and non‐B non‐C (NBNC) in 24] who underwent curative resection for HCC were included. The cumulative recurrence rate was compared according to the etiology of the underlying hepatitis and was stratified by tumor size and other clinicopathologic parameters. Altogether, 116 patients (47%) had a tumor recurrence within 17 ± 11 months after resection. No significant difference in recurrence was noted among the four groups of patients (HBV, HCV, HBV+HCV, NBNC) (p = 0.248). Persistent hepatitis was more common in the HCV group (p < 0.001) after resection. Among the 157 patients with a small (= 5 cm) tumor, the recurrence rate was significantly higher in the HCV group than in the HBV, HBV+HCV, and NBNC groups (p = 0.036). Cox multivariate analysis showed that HCV infection [relative risk (RR) 4.4, 95% confidence interval (CI) 1.3–14.8, p = 0.018] and vascular invasion (RR 3.2, 95% CI 1.2–8.9, p = 0.044) were independent predictors of tumor recurrence. Stratified analysis in other parameters did not show significant differences in terms of tumor recurrence among the four virologic groups (p > 0.1 for all parameters). In conclusion, patients with small HCCs and concurrent HCV infection are at a high risk of tumor recurrence after resection.
Palliation of Malignant Gastroduodenal Obstruction with Open Surgical Bypass or Endoscopic Stenting: Clinical Outcome and Health Economic Evaluation
Authors: Johnsson Erik , Thune Anders , Liedman Bengt
Published: August 2004

Gastroduodenal outlet obstruction is a complication of advanced gastrointestinal malignant disease. In the past it was usually treated by an open surgical bypass procedure. During the last decade, endoscopic self‐expandable stents (SEMS) have been used. The aim of this study was to compare these two palliative strategies concerning clinical outcome and health economy. A series of 36 patients with incurable malignant disease and gastroduodenal outlet obstruction syndrome were treated in a prospective study. According to the attending hospital and endoscopist on duty, 21 of the 36 patients were endoscopically treated with SEMS and 15 underwent an open surgical gastroenteroanastomosis. Health economic evaluation was based on the monetary charges for each patient associated with the procedure, postoperative care, and hospital stay. The hospital stay was 7.3 days for the stented group compared with 14.7 days for the open surgery group (p > 0.05). The survivals were 76 and 99 days, respectively (NS). In the stented group all 15 patients (100%) alive after 1 month were able to eat or drink, and 11 (73%) of them tolerated solid food. In the surgical bypass group,9 out of 11 (81%) patients alive after 1 month could eat or drink, and 5 of them (45%) could eat solid food. The mean charges (U.S. dollars) during the hospital stay were $7215 for the stented group and $10,190 for the open surgery group (p < 0.05). Palliation of the gastroduodenal obstruction in patients with malignant disease were at least as good, and the charges were lower for the endoscopic stenting procedure than for an open surgical bypass.
Recurrent Laryngeal Nerve Identification and Assessment during Thyroid Surgery: Laryngeal Palpation
Authors: Randolph Gregory W. , Kobler James B. , Wilkins Jamie
Published: August 2004

Electrical identification and monitoring of the recurrent laryngeal nerve (RLN) has been proposed as an adjunct to standard visual identification of the nerve during thyroid and parathyroid surgery. This study was undertaken to assess laryngeal palpation as an intraoperative technique for identifying and assessing the RLN during surgery and to investigate the relation between laryngeal palpation and associated laryngeal electromyographic (EMG) activity. The postcricoid region of the larynx during surgery was palpated through the posterior hypopharyngeal wall to sense posterior cricoarytenoid muscle contraction in response to ipsilateral RLN stimulation (i.e., the “laryngeal twitch response.”) Laryngeal palpation was performed in a series of 449 consecutive thyroid and parathyroid surgeries with 586 RLNs at risk. All patients underwent preoperative and postoperative laryngoscopy to assess vocal cord mobility. In a subset of patients, laryngeal palpation and simultaneous laryngeal EMG recordings were compared during intraoperative RLN stimulation. In this series, there was no permanent RLN paralysis. There was one case of temporary RLN paralysis secondary to neural stretch that resolved 6 weeks postoperatively (temporary paralysis rate: 0.2% of patients, 0.2% of nerves at risk). Intraoperative laryngeal palpation of the laryngeal twitch response reliably correlated with normal postoperative vocal cord function. Loss of the laryngeal twitch response occurred in the single case of temporary paralysis in the setting of an anatomically intact nerve. Laryngeal palpation correlated well with simultaneous laryngeal EMG activity. There were no palpation‐induced laryngeal injuries or laryngeal edema. There were also no RLN injuries due to repetitive neural stimulation. Intraoperative laryngeal palpation during RLN stimulation is a safe, reliable method for neural monitoring that can assist in RLN identification and assessment during thyroid and parathyroid surgery. Most importantly, it provides important prognostic information regarding ipsilateral vocal cord function at the completion of the initial side of the thyroid or parathyroid surgery. Intraoperative laryngeal palpation allows the surgeon to stage contralateral surgery if RLN damage is diagnosed, thereby avoiding the potential for bilateral vocal cord paralysis. We believe that laryngeal palpation is useful as an adjunct to formal EMG monitoring during thyroid and parathyroid surgery.
Local Anesthesia Use for Laparoscopic Cholecystectomy
Authors: Inan Aydin , Sen Meral , Dener Cenap
Published: August 2004

This study aimed to investigate the effects and timing of local anesthesia during laparoscopic surgery in terms of postoperative pain, nausea, and the need for opioids and antiemetics. This prospective study was carried out on 142 patients who underwent laparoscopic cholecystectomy. Peroperative local anesthesia was not administered to 53 patients (group A). The skin, subcutis, fascia, and parietal peritoneum were infiltrated with 0.5% bupivacaine HCl at trocar sites before trocar insertion in 46 patients (group B). Local anesthesia was given to 43 patients in equal doses at the same sites and the same manner at the end of surgery (group C). The higher requirement for analgesics in group A patients was statistically significant when compared with that in group B and C patients. The mean doses of analgesics postoperatively were significantly higher in group B than in group C. The time delay to the first antiemetics was significantly shorter in group A than in group C. Applying local anesthesia to the skin, subcutis, fascia, and parietal peritoneum through trocar sites reduces the postoperative analgesic requirement and pain intensity. This approach is more effective when applied at the end of an operation than at the start.
Laparoscopic Cholecystectomy as a Day Surgery Procedure: Implementation and Audit of 136 Consecutive Cases in a University Hospital
Authors: Vuilleumier Henri , Halkic Nermin
Published: August 2004

Laparoscopic cholecystectomy (LC) has been routinely performed since 1989 at our institution, and patients were traditionally admitted for 2 days. In 1996 we implemented a protocol for LC as a day surgery procedure at our center. Although initially reported by others, it has not yet been introduced as routine in Switzerland. The objective of this prospective study was to determine acceptability and safety of LC as an outpatient procedure in a university hospital. Data were collected prospectively for 136 LCs between January 1996 and December 2001. Patients were selected for the study if they wanted to go home within less than 24 hours, had no previous jaundice, and had no anesthetic contraindication. Systematic preoperative liver function tests and hepatic ultrasonography were performed. All patients were admitted on the day of operation. LC was performed using a three‐trocar technique. Systematic cholangiography was performed, and all the procedures were completed laparoscopically. There were no common bile duct explorations. Postoperative complications were the following: nausea in seven patients, a minor umbilical hematoma in two. According to patient preference, 101 (74%) were discharged after an overnight stay (less than 24 hours) and 32 (24%) on the same day. The unplanned admission rate was 2%, and none of the patients was subsequently readmitted. The reasons for unplanned admissions were two patients with persistent nausea and one patient for whom an overnight stay was scheduled who presented with a ruptured subcapsular hematoma of the liver. Altogether, 97% of the patients were satisfied with the care they received. Operative costs were not significantly different when comparing inpatient and outpatient LC. The main postoperative savings were in the postoperative costs. Our results confirm that LC as a day surgery procedure is safe, effective, and acceptable to patients and their relatives. These results were achieved by using selection criteria that considered not only the surgical pathology but also the individual and by using appropriate techniques and planned postoperative analgesia.
Outcome of Laparoscopic Cholecystectomy in Patients 80 Years and Older
Authors: Tambyraja Andrew L. , Kumar Sudhir , Nixon Stephen J.
Published: August 2004

Advanced age is associated with an increase in postoperative complications. This study assesses the indications and outcome for laparoscopic cholecystectomy (LC) in patients aged 80 years or older. Consecutive, unselected patients aged 80 years or over undergoing LC between 1991 and 2000 were included. A retrospective case review enabled analysis of clinical and operative factors together with in‐hospital morbidity, 30‐day mortality, and duration of hospital stay. A series of 117 patients, 79 women and 38 men with a median age of 83 years (range 80–93 years), underwent LC. Indications for LC were chronic cholecystitis in 62 (53%) patients, acute cholecystitis in 28 (24%), gallstone pancreatitis in 12 (10%), and other conditions in 15 (13%). Six (5%) patients required conversion to an open procedure. Overall, 26 (22%) patients developed a postoperative complication. There were no bile leaks or bile duct injuries. One patient, with gangrenous cholecystitis, died after LC. The median postoperative hospital stay was 3 days (range 1–31 days). LC can be performed safely with low morbidity in patients over age 80 years.
Effectiveness of Endoscopic Nasobiliary Drainage for Postoperative Bile Leakage after Hepatic Resection
Authors: Terajima Hiroaki , Ikai Iwao , Hatano Etsuro , Uesugi Takehiko , Yamamoto Yuzo , Shimahara Yasuyuki , Yamaoka Yoshio
Published: August 2004

The effectiveness of endoscopic nasobiliary drainage (ENBD) for postoperative bile leakage after hepatic resection was investigated retrospectively. Between 1997 and 2002 a series of 486 hepatectomies without biliary reconstruction were performed. Bile leakage was divided into two categories. Type A was defined as bile leakage communicating with the main bile tree fistulographically or endoscopic cholangiographically, and type B was bile leakage without such a patency of bile flow. Bile leakage developed in 31 patients (6.4%) (types A/B = 16/15). Type A frequently occurred at the major Glisson’s sheath. In contrast, most type B cases occurred at the peripheral bile duct at the cut surface of the liver. Among the type A patients, 10 of 11 were effectively treated with ENBD. For the type B patients, 12 of 15 patients were successfully treated with intraabdominal drainage via surgical drains inserted during the operation or percutaneous tubes newly inserted for biliary fluid collection. ENBD was effective in two of three type B patients. The duration of bile leakage significantly shortened after initiation of ENBD in type A patients (15.3 ± 6.9 vs. 25.8 ± 13.2 days, p < 0.05). The classification based on communication with the main bile tree is useful for determining therapeutic strategy. Type A leakage has a good indication for ENBD, whereas type B can be treated with intraabdominal drainage in most cases, although ENBD may be effective in some intractable type B cases. It is preferable to initiate ENBD as early as possible to shorten the duration of bile leakage and the subsequent hospital stay.