bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuroprotective Effect of Vitamin E Supplementation in Patients Treated With Cisplatin Chemotherapy
Authors: Pace Andrea , Savarese Antonella , Picardo Mauro , Maresca Vittoria , Pacetti Umberto , Del Monte Girolamo , Biroccio Annamaria , Leonetti Carlo , Jandolo Bruno , Cognetti Francesco , Bove Loredana
Published: February 2003

Purpose: The aim of this study is to evaluate the neuroprotective effect of antioxidant supplementation with vitamin E in patients treated with cisplatin chemotherapy.

Methods: Between April 1999 and October 2000, forty-seven patients were randomly assigned to either group one, which received vitamin E supplementation during cisplatin chemotherapy, or to group two, which received cisplatin chemotherapy alone. Alpha-tocopherol (vitamin E; 300 mg/d) was administered orally before cisplatin chemotherapy and continued for 3 months after the suspension of treatment. For preclinical studies, nude mice carrying the human melanoma tumor were treated with cisplatin alone or in combination with vitamin E.

Results: Twenty-seven patients completed six cycles of cisplatin chemotherapy: 13 patients in group one and 14 patients in group two. The incidence of neurotoxicity was significantly lower in group one (30.7%) than it was in group two (85.7%; P < .01). The severity of neurotoxicity, measured with a comprehensive neurotoxicity score based on clinical and neurophysiological parameters, was significantly lower in patients who were supplemented with vitamin E than in patients who were not supplemented with vitamin E (2 v 4.7, P < .01). The results of the preclinical studies showed that when cisplatin was combined with vitamin E, no differences were observed in tumor weight inhibition, tumor growth delay, or life span as compared with treatment with cisplatin alone.

Conclusion: Supplementation of patients receiving cisplatin chemotherapy with vitamin E decreases the incidence and severity of peripheral neurotoxicity.
Utility of Routine Psychological Screening in the Childhood Cancer Survivor Clinic
Authors: Recklitis Christopher , O’Leary Tara , Diller Lisa
Published: February 2003

Purpose: This study examined the utility of routine psychologic screening in a childhood cancer survivor clinic by evaluating patient acceptance, comparing subjects’ symptoms to normative data, examining the utility of specific tests, and identifying risk factors associated with psychological distress.

Methods: During their annual clinic visit, 101 adult survivors of childhood cancer (median age, 25 years) completed the Symptom Checklist 90 Revised (SCL-90), as well as the Short Form 36 (SF-36), Beck Depression Inventory (BDI), and one additional suicide question. Psychological distress was operationally defined according to the published SCL-90 clinical case rule, classifying subjects with a consistent pattern of symptom elevations as clinical cases.

Results: The majority of subjects (80%) completed the screening in less than 30 minutes and reported little (15%) or no (84%) distress. Sixty-four percent believed it would help “very much” or “moderately” in getting to know them, and 35% thought it would help “slightly.” On the SCL-90, 32 subjects (31.7%) had a positive screen, indicating significant psychological distress. All subjects with clinically significant symptoms on the BDI and SF-36 Mental Health Scale were cases on the SCL-90 (case-positive). Suicidal symptoms were reported in 13.9% of the sample, all of whom were SCL-90 cases. In a logistic regression model, subjects’ dissatisfaction with physical appearance, poor physical health, and treatment with cranial radiation were associated with psychological distress.

Conclusion: Results demonstrate that routine psychological screening can be successfully integrated into the cancer survivor clinic and may be effective in identifying those survivors with significant distress who require further evaluation.
Surgery Combined With Peritonectomy Procedures and Intraperitoneal Chemohyperthermia in Abdominal Cancers With Peritoneal Carcinomatosis: A Phase II Study
Authors: Glehen O. , Mithieux F. , Osinsky D. , Beaujard A.C. , Freyer G. , Guertsch Ph. , Francois Y. , Peyrat P. , Panteix G. , Vignal J. , Gilly F.N.
Published: February 2003

Purpose: To evaluate the tolerance of peritonectomy procedures (PP) combined with intraperitoneal chemohyperthermia (IPCH) in patients with peritoneal carcinomatosis (PC), a phase II study was carried out from January 1998 to September 2001.

Patients and Methods: Fifty-six patients (35 females, mean age 49.3) were included for PC from colorectal cancer (26 patients), ovarian cancer (seven patients), gastric cancer (six patients), peritoneal mesothelioma (five patients), pseudomyxoma peritonei (seven patients), and miscellaneous reasons (five patients). Surgeries were performed mainly on advanced patients (40 patients stages 3 and 4 and 16 patients stages 2 and 1) and were synchronous in 36 patients. All patients underwent surgical resection of their primary tumor with PP and IPCH (with mitomycin C, cisplatinum, or both) with a closed sterile circuit and inflow temperatures ranging from 46° to 48°C. Three patients were included twice.

Results: A macroscopic complete resection was performed in 27 cases. The mortality and morbidity rates were one of 56 and 16 of 56, respectively. The 2-year survival rate was 79.0% for patients with macroscopic complete resection and 44.7% for patients without macroscopic complete resection (P = .001). For the patients included twice, two are alive without evidence of disease, 54 and 47 months after the first procedure.

Conclusion: IPCH and PP are able to achieve unexpected long-term survival in patients with bulky PC. However, one must be careful when selecting the patients for such an aggressive treatment, as morbidity rate remains high even for an experienced team.
Treatment-Related Myelodysplasia and Acute Leukemia in Non-Hodgkin’s Lymphoma Patients
Authors: Armitage James O. , Carbone Paul P. , Connors Joseph M. , Levine Alexandra , Bennett John M. , Kroll Stewart
Published: February 2003

Purpose: Standard therapies for non-Hodgkin’s lymphoma (NHL) are associated with an increased risk of developing treatment-related myelodysplastic syndrome or acute myelogenous leukemia (tMDS/AML). However, there is considerable debate over the incidence or risk of tMDS/AML in NHL patients treated with any particular modality and the factors that contribute to malignant transformation.

Design: Conclusions were based on thorough analysis of data reported in the peer-reviewed literature and careful examination of the statistical methodology and methods for identifying cases of tMDS/AML. Unless noted, data are reported only for NHL patients, excluding Hodgkin’s disease patients.

Results: Despite differences in methods used to identify cases and to estimate the cumulative incidence over time (actuarial v cumulative calculations), up to 10% of NHL patients treated with either conventional-dose chemotherapy or high-dose therapy and autologous stem-cell transplantation may develop tMDS/AML within 10 years of primary therapy. Kaplan-Meier estimates of the actuarial incidence, which are based on censoring of patients who died without developing tMDS/AML, can lead to artificially high estimates with large confidence intervals at later time points. Although there is much debate about the cause(s) of tMDS/AML, there is compelling evidence that alkylating agents, certain other leukemogenic agents, and total-body irradiation (TBI) cause chromosomal damage that can lead to tMDS/AML.

Conclusion: Limiting exposure to alkylating agents and eliminating TBI from transplantation conditioning regimens may reduce the relative risk of tMDS/AML.
Perspectives on the Value of American Society of Clinical Oncology Clinical Guidelines as Reported by Oncologists and Health Maintenance Organizations
Authors: Bennett Charles L. , Somerfield Mark R. , Pfister David G. , Tomori Cecilia , Yakren Sofia , Bach Peter B.
Published: February 2003

Purpose: Although the American Society of Clinical Onoclogy’s (ASCO) Health Services Research (HSR) committee activities have primarily focused on clinical guideline development, little is known about the value placed on these guidelines by the desired end users. ASCO members and Health Maintenance Organizations (HMOs) were surveyed on the value and implementation of ASCO guidelines. In this article, we summarize our findings.

Methods: ASCO members (n = 1500) were queried about whether they had read ASCO’s first four clinical guidelines and technology assessment; whether they agreed with the recommendations; whether they used guidelines in clinical practice; and how guidelines had affected reimbursement. HMOs (n = 131) were queried on how they identify, implement, and value the first four ASCO clinical guidelines.

Results: The membership survey indicated that ASCO guidelines were read more often by physicians in private healthcare settings compared with physicians in academic practices (P < .02). Disagreement rates were low for all guidelines (range, 1% to 7%). One quarter of respondents reported that the guidelines were difficult to find and difficult to apply to the practice setting, and approximately one tenth of respondents indicated that the guidelines were difficult to evaluate, interpret, or read. The HMO survey indicated that one third of HMOs reported use of ASCO guidelines, with higher rates of usage by larger HMOs and by those with higher National Committee on Quality Assurance (NCQA) ratings. Respondent HMOs valued guidelines for various purposes and used multiple methods of guideline identification and implementation.

Conclusion: ASCO guidelines are generally highly supported by physicians and HMOs. Additional studies are needed to identify implementation barriers and to see whether guidelines have resulted in improvements in healthcare.
Long-Term Survival of Patients With Supraclavicular Metastases at Diagnosis of Breast Cancer
Authors: Olivotto Ivo A. , Chua Boon , Allan Sharon J. , Speers Caroline H. , Chia Stephen , Ragaz Joseph
Published: February 2003

Background: Patients with supraclavicular metastases at diagnosis of breast cancer were classified between 1987 and 2002 as having stage M1 breast cancer according to the tumor-node-metastasis (TNM) system. The 2003 edition of the TNM staging guidelines has classified such patients as having stage IIIC disease. To determine relative prognosis, we compared long-term survival in a population-based cohort of patients with isolated supraclavicular metastases (nodal-M1) to outcomes of patients with stage IIIB or M1 (other) disease at presentation.

Materials and Methods: Among patients with breast cancer and known tumor stage referred to the British Columbia Cancer Agency from 1976 to 1985, 336 IIIB, 233 M1, and 51 nodal-M1 patients were identified. Actuarial overall and breast cancer–specific survival rates were determined to 20 years.

Results: Overall survival at 20 years was 13.2% for nodal-M1 cases (95% confidence interval [CI], 5% to 26%), 9.4% for IIIB cases (95% CI, 6% to 14%), and 1.3% for M1 (other) cases (95% CI, 0.4% to 3.5%; log-rank P < .0005). Overall survival was similar between nodal-M1 and IIIB cases (P = .27). Breast cancer–specific survival at 20 years was 24.1% for nodal-M1 cases (95% CI, 13% to 37%), 30.2% for IIIB cases (95% CI, 23% to 38%), and 3.9% for M1 (other) cases (95% CI, 2% to 8%; log-rank P < .0005). Breast cancer–specific survival was significantly different for nodal-M1 cases compared with either IIIB or M1 (other) cases (P = .008 for both).

Conclusion: Patients with supraclavicular metastases at diagnosis have significantly better outcomes than patients with M1 (other) disease and overall survival similar to patients with IIIB disease. Reclassification as stage IIIC is appropriate for patients with breast cancer who present with supraclavicular nodal metastases alone.
Regulation of the Rat Follicle-Stimulating Hormone β-Subunit Promoter by Activin
Authors: Suszko Magdalena I. , Lo Denise J. , Suh Hoonkyo , Camper Sally A. , Woodruff Teresa K.
Published: February 2003

FSH is controlled by a variety of positive and negative stimuli, and the unique FSHβ-subunit is a major target for this regulation. Activin is a key modulator of FSHβ transcription and hormone secretion. The signal transduction pathway leading to FSH expression was previously unknown. Here, we show that the transcription factors Smad3 and Smad4 mediate activin-stimulated activity of the rat FSHβ promoter in a pituitary-derived cell line, LβT2. Cells were transiently transfected with the rat FSHβ promoter fused to a luciferase reporter gene (−338rFSHβ-Luc), and a minimal activin-responsive region was identified. Transfection of Smad3, but not the highly related Smad2, led to a ligand-independent stimulation of the FSHβ promoter activity. As expected, activin caused an additional increase of luciferase expression, which was blocked by cotreatment with follistatin. Although Smad4 alone had no effect on FSHβ transcription, it significantly augmented Smad3 and activin-mediated stimulation of the promoter. A palindromic consensus Smad-binding element in the proximal promoter was found to bind Smad4, and elimination of the region resulted in a loss of activin-mediated FSHβ transcription.

The activin signaling pathway is conserved in a number of cells, but FSHβ expression is restricted to gonadotropes. A pituitary-specific transcription factor necessary for activin-dependent induction of the FSHβ promoter has been identified that permits FSHβ expression in nongonadotrope cells. Pitx2 is a member of Pitx subfamily of bicoid-related homeodomain factors that is required for pituitary development and is present in the adult pituitary. This factor was transfected into LβT2 cells, where it caused up-regulation of basal and activin-mediated FSHβ promoter activity. Furthermore, cotransfection of Pitx2c with Smad3 in kidney-derived TSA cells resulted in activin-regulated FSHβ response, suggesting its important role in tissue-restricted regulation of FSHβ by activin. A Pitx2c binding site was identified within the proximal promoter, and elimination of this region also resulted in a loss of activin-regulated FSHβ promoter activity. Taken together, these studies suggest that the regulation of FSHβ is dependent on activin-mediated signaling factors in concert with pituitary-derived nuclear regulatory proteins.
Local Insulin-Like Growth Factor-II Mediates Prolactin-Induced Mammary Gland Development
Authors: Hovey Russell C. , Harris Jessica , Hadsell Darryl L. , Lee Adrian V. , Ormandy Christopher J. , Vonderhaar Barbara K.
Published: February 2003

Prolactin (PRL) is a major determinant of mammary epithelial cell proliferation during alveolar development in sexually mature and pregnant mice. To date, it has not been clear whether PRL effects these responses alone or by also invoking the action of autocrine/paracrine growth factors. In this study, we provide evidence that part of the effect of PRL on mammary gland growth is mediated by IGF-II. During sexual maturity and in early pregnancy, the level of IGF-II mRNA in the mammary gland was increased concurrent with increased PRL receptor expression. The level of IGF-II mRNA was reduced in mammary tissue from PRL receptor−/− mice during early pregnancy, and explants of mouse mammary gland and HC11 mammary epithelial cells both increased their expression of IGF-II after exposure to PRL in vitro. These findings coincided with the demonstration that IGF-II stimulated alveolar development in mammary glands in whole organ culture. PRL was most efficacious in stimulating IGF-II gene transcription from promoter 3 of the mouse IGF-II gene in vitro. Insight into the mechanism by which PRL induced IGF-II expression was provided by the fact that it was blocked by the Jak2 inhibitor AG490 and the MAPK inhibitor PD98059. Finally, induction of insulin receptor substrate (IRS)-1 in the mammary glands of PRL-treated mice and induction of IRS-1 and IRS-2 after treatment with PRL plus progesterone indicates that these molecules are induced by PRL as potential signaling intermediates downstream from IGF-I/insulin receptors. Together, these data demonstrate a role for IGF-II as a mediator of PRL action in the mouse mammary gland during ductal branching and alveolar development.
Insulin-Like Growth Factor I Receptor Signaling and Nuclear Translocation of Insulin Receptor Substrates 1 and 2
Authors: Sun HongZhi , Tu Xiao , Prisco Marco , Wu An , Casiburi Ivan , Baserga Renato
Published: February 2003

The insulin receptor substrate 1 (IRS-1) can translocate to the nuclei and nucleoli of several types of cells. Nuclear translocation can be induced by an activated insulin-like growth factor 1 receptor (IGF-IR), and by certain oncogenes, such as the Simian virus 40 T antigen and v-src. We have asked whether IRS-2 could also translocate to the nuclei. In addition, we have studied the effects of functional mutations in the IGF-IR on nuclear translocation of IRS proteins. IRS-2 translocates to the nuclei of mouse embryo fibroblasts expressing the IGF-IR, but, at variance with IRS-1, does not translocate in cells expressing the Simian virus 40 T antigen. Mutations in the tyrosine kinase domain of the IGF-IR abrogate translocation of the IRS proteins. Other mutations in the IGF-IR, which do not interfere with its mitogenicity but inhibit its transforming capacity, result in a decrease in translocation, especially to the nucleoli. Nuclear IRS-1 and IRS-2 interact with the upstream binding factor, which is a key regulator of RNA polymerase I activity and, therefore, rRNA synthesis. In 32D cells, wild-type, but not mutant, IRS-1 causes a significant activation of the ribosomal DNA promoter. The interaction of nuclear IRS proteins with upstream binding factor 1 constitutes the first direct link of these proteins with the ribosomal DNA transcription machinery.
Workspace analysis and performance of a binary actuated parallel manipulator with flexural joints
Authors: Ottaviano E , Carbone G , Ceccarelli M
Published: February 2003

In this paper the design of a miniaturized parallel architecture is investigated in terms of basic performances concerning mobility and workspace characteristics. The miniature requirements have been achieved with a milli-scaled parallel manipulator requiring flexural joints and binary actuation with shape memory alloy wires or small pneumatic pistons. The mechanical design is analysed by considering the mobility of the flexural joints in order to size them and model the kinematics of the joints. The reachability is analysed through a suitable formulation of the direct kinematics by also taking into account binary actuation. Workspace performance has been determined in terms of position and orientation capabilities.
Synchronization of chaotic symmetric gyros by one-way coupling conditions
Authors: Chen H-K , Lin T-N
Published: February 2003

A simple satellite is a symmetric gyro. Satellites are used for communications, weather forecasts, surveying and in several other scientific and military applications. In particular, for military use secure communications are very important. As chaotic signals are usually broadband and noise like, synchronized chaotic systems can be used as cipher generators for secure communication. This paper presents chaos synchronization of two identical chaotic motions of symmetric gyros. It has been demonstrated that applying four different kinds of one-way coupling conditions can synchronize two identical chaotic systems. The sign of the sub-Liapunov exponent has been used as an indicator for the occurrence of chaos synchronization. It has also been found that when chaos synchronization occurs the positive major sub-Liapunov exponent transverses the zero value and becomes negative for the last time. Chaos synchronization can also be shown by phase trajectory. In addition, synchronization time is also examined. Furthermore, it has been found that different distances of the initial conditions between the master system and slave system do not affect the occurrence of chaos synchronization.
Dynamic characteristics of stacked piezoelectric transducers of ultrasonic wire bonders used in integrated circuit packaging
Authors: Hu C M , Guo N , Du H , Xu L M
Published: February 2003

Currently ultrasonic wire bonders with precision capillary tips are widely used for bonding wires to integrated circuit (IC) chips and circuits. However, the quality and strength of a bond may be affected significantly by the change of vibration during the bonding process. It is therefore important to understand the dynamics of the bonding process as well as the vibration characteristics of the bonding system, so bonding quality may be monitored. This paper reports the study on the dynamic characteristics of the stacked piezoelectric transducers used in the ultrasonic wire bonding system. The vibration characteristics are first analysed using the finite element method with resonant frequency and vibration modes. The predicted impedance response is compared with the measurement using a high-pressure (HP) impedance analyser. The displacement profile along the transducer assembly, which includes a piezoelectric stack, clamping and horn sections, are also analysed. The effects of multilayer and polarization on the response of the transducer are discussed. It was found there is good agreement between the prediction and measurement, and bending and extension modes may be excited differently according to the polarization configuration used in the multilayer stack.
Eddy genesis and transformation of Stokes flow in a double-lid driven cavity
Authors: Gürcan F , Gaskell P H , Savage M D , Wilson M C T
Published: February 2003

Stokes flow is considered in a rectangular driven cavity of depth 2 H and width 2 L, with two stationary side walls and two lids moving in opposite directions with speeds U1 and U2. The flow is governed by two control parameters: the cavity aspect ratio, A = H/L, and the speed ratio, S = U1/ U2.

The solution for the streamfuntion is expressed as an infinite series of Papkovich-Faddle eigenfunctions, which is then expanded about any stagnation point to reveal changes in the local flow structure as A and S are varied. An (S, A) control space diagram is constructed, which exhibits an intricate structure due to the intersection and confluence of several critical curves representing flow bifurcations at degenerate critical points. There are eight points where two critical curves intersect and the flow bifurcations are described and interpreted with reference to the theoretical work of Bakker ( Bifurcations in Flow Patterns, Kluwer Academic, 1991) and Brøns and Hartnack ( Phys. Fluids, 1999, 11, 314).

For a speed ratio in the range -1 ≤ S < O the various flow trnsformations are tracked as A increases in the range O < A < 3.2, and hence the means is identified by which new eddies appear and become fully developed. It is shown that for S ≠ O, the number of eddies increases from 1 to 3 via several key flow transformations, which become more complicated as | S| is reduced.
Predicting the flow field inside a close-coupled catalyst—the effect of entrance losses
Authors: Benjamin S F , Zhao H , Arias-Garcia A
Published: February 2003

A methodology is described for improving the prediction of the flow distribution in automotive close-coupled catalysts using computational fluid dynamics (CFD). Steady and pulsating flow simulations have been performed and compared with measurements obtained on an isothermal flow rig. By incorporating an extra pressure loss due to oblique entry at the monolith improved flow predictions are obtained. This work extends the methodology that has previously been developed for axisymmetric systems.
The Dynamic Performance of a Composite Blade from a 5kW Wind Turbine Part II: Predicted Blade Response
Authors: Bechly M. E. , Clausen P. D.
Published: February 2003

This paper presents analytical and computational predictions of the performance of an operating 2.5 m long composite wind turbine blade and compares these predictions with the results of detailed measurements. Part 1 of this paper describes in detail the important aspects of the 5 kW wind turbine, the experimental equipment and data acquisition procedures and presents and discusses some of the results from the experimental data. Here the analytical methodology of Eggleston and Stoddard (1987) and the solutions from the computational wind turbine software package Bladed, were used to predict the performance of the blade for a particular set of experimental conditions. The solutions of Eggleston and Stoddard, where only the first order dynamic equations of a simplified blade model are solved, underestimate the root flapwise moment, streamwise blade tip deflection and lead-lag tip deflection, but gave fairly accurate predictions for the blade lead lag moment. The turbine's structural dynamics within Bladed used a more accurate model of the blade and solved the structural dynamic equations by implementing modal analysis. The results gave root flapwise moment of the same order as those determined from the measurements, close agreement with the measured lead-lag moment, a slight underprediction of the flapwise tip deflection and large under prediction of the lead-lag tip deflection. The under prediction of the lead-lag deflection by both methods is likely to be due to the uncoupling of the lead-lag and flapping motions, and the unusual shape of the blade close to its root connection.
Offshore Wind Energy – the Technical Challenge; Report of conference S868, Institution of Mechanical Engineers, London
Authors: Twidell John W.
Published: February 2003

As Denmark and Sweden, the UK is enthusiastically progressing the option of significant power generation from offshore windfarms. This paper reviews, with permission, the UK situation as presented by speakers at a recent conference (reference S868) organised by the UK Institution of Mechanical Engineers. Each section gives a summary, with data, of the presentations by the named speakers. By 2010, offshore windfarms to a total investment of £ 4 billion (6.5 billion Euro) can be expected in UK waters.
Effects of a Femoral Shaft Fracture on Multiply Injured Patients with a Head Injury
Authors: Nau Thomas , Kutscha‐Lissberg Fritz , Muellner Thomas , Koenig Franz , Vecsei Vilmos
Published: February 2003

Abstract

To study the effects of a femoral shaft fracture and its early stabilization on the morbidity, mortality, and outcome of patients with multiple injuries and a concomitant head injury, we analyzed the clinical course of patients using a prospectively gathered database. A series of 42 patients with multiple injuries, including head injuries and femoral fractures, formed the study group. A series of 133 patients with multiple injuries and head injuries but without femoral fractures formed the control group. The parameters examined included injury severity, injury pattern, hemodynamics at admission, mortality, duration of ventilation, length of intensive care unit (ICU) stay, and outcome. There were no significant differences regarding the demographics, injury severity score (ISS), injury pattern except the extremity Abbreviated Injury Scale (AIS) between the study and control groups. No significant differences were found in terms of mortality, duration of ventilation/ICU stay, and outcome. Injury severity (ISS), severity of the head injury (AIS), and hemodynamics at admission were shown to have a significant effect on the examined parameters. The present study suggests that a femoral fracture and its early stabilization in a multitrauma patient with a concomitant head injury do not adversely affect mortality and outcome and supports aggressive surgical management for these patients.
Management of 100 Consecutive Cases of Pancreatic Serous Cystadenoma: Wait for Symptoms and See at Imaging or Vice Versa?
Authors: Bassi Claudio , Salvia Roberto , Molinari Enrico , Biasutti Carlo , Falconi Massimo , Pederzoli Paolo
Published: February 2003

Abstract

Pancreatic serous cystadenomas have a low malignancy rate. When nonsymptomatic, in selected patients, they can be managed without surgery; however, a high degree of diagnostic reliability is crucial. We admitted 100 consecutive cases (87 women with a median age of 51.86 years). Of these, 44 were symptomatic and 56 were diagnosed incidentally. Ultrasound correctly diagnosed 53% of the cases, incorrectly 31%, and was nondiagnostic in 16%. Computed tomography scan had similar rates (54%, 34% and 12%, respectively), while magnetic resonance imaging improved diagnostic accuracy to 74% and reduced incorrect diagnoses to 26%. In 21 cases, exploratory needle aspiration of the cyst was carried out; only 8 samples (38%) resulted in a diagnosis; in 12 patients (57%) insufficient material was acquired to allow for diagnosis, one case demonstrated epithelial dysplasia. In 1 patient an exploratory puncture resulted in a very serious bleeding. Sixty‐eight patients were treated surgically, the 44 symptomatic cases and another 24 patients with ill‐defined oligocystic lesions that could not be differentiated as serous or mucinous in the preoperative period. Two patients underwent resection because of frank tumor growth. In the two time periods analyzed (the first 7 years and the subsequent 6.5 years) the relationship between cases observed/operated on did not significantly change. Twenty‐one (30.8%) distal pancreatectomies, 14 (20.5%) intermediate resections, 10 (14.7%) pancreaticoduodenectomies 4 (5.8%) enucleations, and 1 (1.4%) duodenum‐preserving pancreatic head resection were carried out. Nine patients (13.2%), underwent exploratory laparotomy with a diagnostic biopsy. Another 9 underwent decompressive interventions with cystojejunostomies. The morbidity was 27.9%, with a reoperation rate of 7.3% and zero mortality. In general the patient’s pain resolved in the postoperative period. Median follow‐up was 43 months (range, 4–191 months). One patient died from other causes, and all others are currently alive. In the group of 32 patients who did not undergo operation, the median follow‐up is 69 months (range, 8–164 months). Until more sophisticated technologies can be developed, the current diagnostic work‐up will not result in increased preoperative diagnosis of serous‐cystic tumors of the pancreas. This is mainly relevant to the oligocystic forms, which account for about one fourth of all serous tumors observed.
Evaluating the Hilar Bifurcation Territory in the Human Liver Caudate Lobe to Obtain Critical Information for Delimiting Reliable Margins during Caudate Lobe Surgery: Anatomic Study of Livers with and without the External Caudate Notch
Authors: Kanamura Tetsuhiro , Murakami Gen , Ko Saiho , Hirai Ichiro , Hata Fumitake , Nakajima Yoshiyuki
Published: February 2003

Abstract

The hilar bifurcation (HB), a wedged portion between the left and right portal vein origins, often issues the caudate branch. However, the HB territory in the caudate lobe has not been well recognized during liver surgery. In 50% of 48 human livers (25 usual livers and 23 with the external caudate notch), the HB gave off thick portal branches (> 1 mm) to supply the caudate lobe. Using minute dissections, we identified four cross‐sectional configurations of three subdivisions of the caudate lobe (i.e., left, right, and HB portal territories). The HB territory was consistently located in the paracaval portion, although it sometimes (29.2%: type A) extended slightly or deeply into Spiegel’s lobe. This leftward HB territorial extension was seen more frequently in livers with the notch (43.6%) than in those without it (“usual” livers) (16.0%). Moreover, in livers with the notch the caudate lobe (usually its right portal territory) tended to extend upward and rightward to attach or surround the terminal portion of the right hepatic vein. Our results suggested that in many cases subdivisions of the caudate lobe cannot be divided simply into right and left portions. The HB branch or territory should be examined to determine the real principal border as well as the subdivisional configuration of the caudate lobe. Combined evaluation of the HB branch(es) and external notch could provide critical information for anatomically sophisticated caudate lobe surgery.
Completion Radical Surgery after Cholecystectomy for Accidentally Undiagnosed Gallbladder Carcinoma
Authors: Toyonaga Takayuki , Chijiiwa Kazuo , Nakano Kenji , Noshiro Hirokazu , Yamaguchi Koji , Sada Masayuki , Terasaka Reiji , Konomi Kohki , Nishikata Fujihiko , Tanaka Masao
Published: February 2003

Abstract

Survival time of 73 patients with undiagnosed gallbladder carcinoma incidentally found after cholecystectomy treated between 1982 and 2000 was evaluated in relation to various variables, with special reference to the significance of the radical second resection. The most significant prognostic factor was the depth of tumor invasion as assessed by univariate and multivariate analyses (odds ratio 3.40, 95% CI 1.65–7.00, p < 0.001). None of the 23 pT1 patients received radical second resection, and all of them were doing well without recurrence at their last follow‐up examination. The 3‐year survival rate was 68% for patients with pT2 and 14% for patients with pT3. Patient characteristics for the 18 pT2 patients who underwent radical second resection were similar to the characteristics of the 25 pT2 patients who did not; nor did postoperative survival times differ significantly. Survival time was not correlated with the interval from initial to second surgery or the type of initial cholecystectomy (open vs laparoscopic). In 11 patients with pT2 whose surgical margin was judged positive at initial cholecystectomy, the radical second resection significantly lengthened survival time. Radical second resection tended to prolong the median survival period from 7 to 15 months in 7 patients with pT3, although the difference was not significant. In conclusion, patients with pT1 undiagnosed carcinoma need no further treatment. The redo surgery was found to prolong survival only in patients with pT2 with positive surgical margin at initial cholecystectomy.
Possibilities of Chromoesophagoscopy for Diagnosis of Barrett’s Esophagus
Authors: Khadjibaev Abdukhakim M. , Nizamkhodjaev Zaynuddin M. , Kholmatov Rustam M. , Mirzakhmedov Bokhodir M. , Mirzaev Botir B.
Published: February 2003

Abstract

When the distal esophagus is covered with columnar gastric mucosa up to 2 cm from the esophagogastric junction it is considered normal. If the distal esophagus is covered with columnar epithelium more than 2 cm from the esophagogastric junction, it is called Barrett’s esophagus. We have developed a new chromoesophagoscopic method to improve diagnostic testing for Barrett’s esophagus. The distinctive feature of this method is that 4 to 5 ml of a 1% solution of neutral red is administered intravenously, after which excretion of the stain by the esophageal mucosa is examined by endoscopy. Chromoesophagoscopy has been carried out in 11 patients with reflux esophagitis. It revealed Barrett’s esophagus in four patients, which was proved by histologic evaluation of biopsy specimens obtained from the stained zone of the esophageal mucosa. These observations suggest that chromoesophagoscopy is an effective, accessible, feasible, safe method for diagnosing Barrett’s esophagus. It allows us to determine the length of the metaplastic epithelium and the topography of gastric glands; it also allows us to examine parietal cells in the esophagus and estimate the functional activity of these parietal cells in metaplastic epithelium.
Long‐term Results of Partial Pancreaticoduodenectomy for Ductal Adenocarcinoma of the Pancreatic Head: 25‐Year Experience
Authors: Richter Axel , Niedergethmann Marco , Sturm Jörg W. , Lorenz Dietmar , Post Stefan , Trede Michael
Published: February 2003

Abstract

The prognosis of patients who undergo resection for pancreatic ductal adenocarcinoma with curative intention is generally poor unless they have early‐stage disease. Based on our 25‐year experience, the results of 194 patients after a standardized Kausch‐Whipple resection for adenocarcinoma of the pancreatic head were analyzed and the prognostic factors were evaluated. Between 1972 and 1998 a total of 221 patients were diagnosed for ductal adenocarcinoma of the pancreatic head, and 194 of them subsequently underwent a standardized Kausch‐Whipple resection. Long‐term results and prognostic factors were examined by multivariate and univariate analyses. The overall postoperative mortality was 3.09%, and the morbidity was 29.9%. By multivariate analysis only curative resection (R0) was significantly related to a favorable prognosis (p < 0.0001). Furthermore, in case of a curative resection, the presence of lymph node metastases showed prognostic significance in the multivariate analysis (p = 0.005). Cumulative survival analysis revealed a 5‐year survival rate of 25.4%, a 7‐year survival rate of 12.3%, and a 10‐year survival rate of 8.2% for patients who underwent curative resection (R0) for adenocarcinoma of the pancreatic head. We demonstrated that the R0 status is the only independent prognostic factor after surgery for adenocarcinoma of the pancreatic head. In the case of a curative resection, the presence of lymph node metastases is of prognostic relevance. In view of considerable surgical morbidity and mortality, resection for cancer of the pancreatic head is the only option if the lesion is resectable. We concluded that surgical treatment is “as good as it gets,” as extended techniques have not proved to produce better results.
Hepatic Resection for Colorectal Metastasis with Macroscopic Tumor Thrombus in the Portal Vein
Authors: Tada Keiichiro , Kokudo Norihiro , Seki Makoto , Ueno Masashi , Azekura Kaoru , Ohta Hirotoshi , Yamaguchi Toshiharu , Matusbara Toshiki , Takahashi Takashi , Nakajima Toshifusa , Yanagisawa Akio , Muto Tetsuichiro
Published: February 2003

Abstract

Metastatic lesions in the liver derived from colorectal cancer rarely invade the portal vein macroscopically. Little is known about the clinical characteristics and outcome of surgical treatment in patients with tumor thrombus in the portal vein. Medical charts of 142 consecutive patients who underwent hepatic resection for colorectal metastasis were reviewed retrospectively. Of the 142 patients, 4 (2.8%) had macroscopic portal vein invasion. The most prominent characteristic on preoperative imaging was segmental staining in the arterial phase shown by dynamic computed tomography (CT) or by CT arteriography. This finding was positive in all four of the patients. All patients underwent anatomic liver resection and were alive with no evidence of disease for an average of 52.3 months (range 21–102 months). Macroscopic tumor thrombus in the portal vein is rare with colorectal metastasis. It is accurately detected by CT by checking for signs of segmental staining. In this setting, anatomic major resection of the liver is essential for curative treatment.
Surgical Therapy and Histological Abnormalities in Functional Isolated Small Bowel Obstruction and Idiopathic Gastrointestinal Perforation in the Very Low Birth Weight Infant
Authors: Miserez Marc , Barten Suzanna , Geboes Karel , Naulaers Gunnar , Devlieger Hugo , Penninckx Freddy
Published: February 2003

Abstract

We examined surgical treatment, outcome, and histological findings in very low birth weight (VLBW) infants with functional isolated small bowel obstruction (FISBO) and idiopathic gastrointestinal perforation (IGIP). The files of 18 neonates (average gestational age 27.5 weeks; average birth weight 880 g), surgically treated for IGIP (n = 12) or FISBO (n = 6), were retrospectively reviewed. In both groups segmental or diffuse dilatation of the small bowel was seen. All but two perforations were localized in the small bowel. In half of the patients a discontinuous absence of the internal layer of the muscularis propria or muscularis mucosae was found. Signs of necrotizing enterocolitis (NEC) were absent. Most of the patients were treated with an enterostomy (IGIP: n = 11; FISBO: n = 4). Overall survival in both groups was 83%. Follow‐up after enterostomy closure (mean 23 months) shows normal gastrointestinal function without failure to thrive in 67% of the survivors. Muscular wall abnormalities and small bowel distension are found in both FISBO and IGIP. Although the underlying etiology remains unclear, segmental muscular wall absence may be a major predisposing factor in both conditions. Creation of a temporary enterostomy is a valid surgical option in VLBW infants with minimal risk for recurrent obstruction and/or perforation. Survival and long‐term gastrointestinal function is excellent. IGIP should be distinguished from NEC.
Is Adenocarcinoma of the Gastric Cardia a Distinct Entity Independent of Subcardial Carcinoma?
Authors: Ichikura Takashi , Ogawa Toshiya , Kawabata Toshinobu , Chochi Kentaro , Sugasawa Hidekazu , Mochizuki Hidetaka
Published: February 2003

Abstract

Cardia carcinoma has been defined diversely. The purpose of this study was to determine whether cardia carcinoma should be categorized as a distinct entity independent of subcardial carcinoma. We retrospectively analyzed 65 patients undergoing resection for adenocarcinoma involving the esophagogastric junction (EGJ) with the tumor center within 5 cm of the EGJ. Adenocarcinomas of the EGJ were classified into Type I, Type II, and Type III according to Siewert’s criteria. There was only one Type I adenocarcinoma, and it was associated with Barrett’s esophagus. No tumors had their center between 1 cm and 2 cm proximal to the EGJ. Clinicopathologic features and prognosis were compared among patients with Type II adenocarcinomas (n = 31), patients with Type III adenocarcinomas (n = 33), and patients with adenocarcinomas in the upper third of the stomach not invading the EGJ (n = 153). Siewert’s Type II adenocarcinoma was associated with a higher male/female ratio and with higher incidences of well‐demarcated appearance and differentiated histology than carcinoma of the upper third of the stomach without esophageal invasion. Lymph nodes along the greater curvature and parapyloric nodes were rarely involved in Type II tumors. Within the pT2 category, patients with Siewert’s Type II tumors showed a higher incidence of lymph node metastasis and a significantly lower survival rate than did patients with tumors of the upper third of the stomach without esophageal invasion. In conclusion, cardia carcinoma, appropriately defined as adenocarcinoma with its epicenter between 1 cm proximal and 2 cm distal to the EGJ, should be categorized as a distinct entity.
Catalytic function of Drosophila melanogaster glutathione S‐transferase DmGSTS1‐1 (GST‐2) in conjugation of lipid peroxidation end products
Authors: Singh Sharda P. , Coronella Julia A. , Beneš Helen , Cochrane Bruce J. , Zimniak Piotr
Published: February 2003

Drosophila melanogaster glutathione S‐transferase DmGSTS1‐1 (earlier designated as GST‐2) is related to sigma class GSTs and was previously described as an indirect flight muscle‐associated protein with no known catalytic properties. We now report that DmGSTS1‐1 isolated from Drosophila or expressed in Escherichia coli is essentially inactive toward the commonly used synthetic substrate 1‐chloro‐2,4‐dinitrobenzene (CDNB), but has relatively high glutathione‐conjugating activity for 4‐hydroxynonenal (4‐HNE), an electrophilic aldehyde derived from lipid peroxidation. 4‐HNE is thought to have signaling functions and, at higher concentrations, has been shown to be cytotoxic and involved in the etiology of various degenerative diseases. Drosophila strains carrying P‐element insertions in the GstS1 gene have a reduced capacity for glutathione conjugation of 4‐HNE. In flies with both, one, or none of the GstS1 alleles disrupted by P‐element insertion, there is a linear correlation between DmGSTS1‐1 protein content and 4‐HNE‐conjugating activity. This correlation indicates that in adult Drosophila 70 ± 6% of the capacity to conjugate 4‐HNE is attributable to DmGSTS1‐1. The high abundance of DmGSTS1‐1 (approximately 2% of the soluble protein in adult flies) and its previously reported localization in tissues that are either highly aerobic (indirect flight muscle) or especially sensitive to oxidative damage (neuronal tissue) suggest that the enzyme may have a protective role against deleterious effects of oxidative stress. Such function in insects would be analogous to that carried out in mammals by specialized alpha class glutathione S‐transferases (e.g. GSTA4‐4). The independent emergence of 4‐HNE‐conjugating activity in more than one branch of the glutathione S‐transferase superfamily suggests that 4‐HNE catabolism may be essential for aerobic life.
Chloromethane:tetrahydrofolate methyl transfer by two proteins from Methylobacterium chloromethanicum strain CM4
Authors: Studer Alex , Stupperich Erhard , Vuilleumier Stéphane , Leisinger Thomas
Published: February 2003

The cmuA and cmuB genes are required for growth of Methylobacterium chloromethanicum strain CM4 with chloromethane as the sole carbon source. While CmuB was previously shown to possess methylcobalamin:tetrahydrofolate methyltransferase activity, sequence analysis indicated that CmuA represented a novel and so far unique two‐domain methyltransferase/corrinoid‐binding protein involved in methyl transfer from chloromethane to a corrin moiety. CmuA was purified from wild‐type M. chloromethanicum strain CM4 and characterized as a monomeric, cobalt‐containing and zinc‐containing enzyme of molecular mass 67 kDa with a bound vitamin B12 cofactor. In combination, CmuA and CmuB proteins catalyze the in vitro transfer of the methyl group of chloromethane to tetrahydrofolate, thus affording a direct link between chloromethane dehalogenation and core C1 metabolism of Methylobacterium. Chloromethane dehalogenase activity in vitro is limited by CmuB, as formation of methyltetrahydrofolate from chloromethane displays apparent Michaelis–Menten kinetics with respect to methylated CmuA, with an apparent Km of 0.27 µm and a Vmax of 0.45 U·mg−1. This contrasts with sequence‐related systems for methyl transfer from methanogens, which involve methyltransferase and corrinoid protein components in well‐defined stoichiometric ratios.
Age‐dependent decrease in adenosine A1 receptor binding sites in the rat brain
Authors: Cunha Rodrigo A. , Constantino M. Dolores , Fonseca Ema , Ribeiro J. A.
Published: February 2003

Unsaturated free fatty acids and adenosine operate two neuromodulatory systems with opposite effects on neuronal function. Here, we tested if fatty acids controlled inhibitory adenosine A1 receptors. Arachidonate (AA, 10 µm) decreased the Bmax of an A1 receptor agonist, (R)‐[3H]phenylisopropyladenosine (PIA; from 812 to 267 fmol·mg−1 protein), and antagonist, [3H]1,3‐dipropyl‐8‐cyclopentylxanthine (DPCPX; from 994 to 311 fmol·mg−1 protein) and decreased the Kd of [3H]PIA (from 1.20 to 0.57 nm) binding to brain membranes of young adult rats (2 months old), these effects being mimicked by other cis but not trans unsaturated or saturated fatty acids. AA (10 µm) increased the potency of the A1 receptor agonist, 2‐chloroadenosine to inhibit hippocampal synaptic transmission in young adult rats (EC50 decreased from 337 to 237 nm), which may constitute a safety feedback mechanism to control AA‐induced neurotoxicity. Upon aging, there were increased free fatty acid levels and a concomitant decreased density of A1 receptors. This was more marked in hippocampal nerve terminals of aged rats (24 months old) and may be the determinant factor contributing to the lower potency of 2‐choloroadenosine in aged rats (EC50 = 955 nm), in spite of the decreased Kd of PIA binding upon aging. The effects of AA on A1 receptor binding were attenuated upon aging, AA being devoid of effects in aged rats. Accordingly, AA (10 µm) failed to modify the potency of 2‐choloroadenosine in aged rats (EC50 = 997 nm). However, albumin, which quenches free fatty acids, increased A1 receptor density by 65% and 2‐chloroadenosine potency (EC50 = 703 nm) in aged rats, suggesting that the increased fatty acids levels in aged rats may contribute to the decreased potency of A1 receptor agonists in aged rats. Also, the observed saturation of the control by AA of A1 receptors may contribute to the decreased adaptability of neuromodulation to different firing conditions in aged rats.