bluuebunny/crossref_metadata_2025 huggingface dataset:
Surgical management of abdominal and retroperitoneal Castleman's disease
Authors: Bucher Pascal , Chassot Gilles , Zufferey Guillaume , Ris Frederic , Huber Olivier , Morel Philippe
Published: June 2005

Background

Abdominal and retroperitoneal Castleman's disease could present either as a localized disease or as a systemic disease. Castleman's disease is a lymphoid hyperplasia related to human Herpes virus type 8, which could have an aggressive behavior, similar to that of malignant lymphoid neoplasm mainly with the systemic type, or a benign one in its localized form.

Methods

The authors report two cases of localized Castleman's disease in the retroperitoneal space and review the current and recent progress in the knowledge of this atypical disease.

Cases presentation

The two patients were young healthy women presenting with a hyper vascular peri-renal mass suggestive of malignant tumor. Both have been resected in-toto. One of them had an extensive resection with nephrectomy, while the second had a kidney preserving surgery. Pathological examination revealed localized Castleman's disease and surgical margins were free of disease. Postoperative course was uneventful, and after more than 5-years of follow-up no recurrences have been observed.

Conclusion

Localized Castleman's disease should be considered when facing a solid hypervascular abdominal or retroperitoneal mass. A better knowledge of this disorder and its characteristic would help surgeon to avoid unnecessarily extensive resection for this benign disorder when dealing with abdominal or retroperitoneal tumors. Surgical resection is curative for the localized form, when complete, while splenectomy could be indicated for the systemic form.
Effect of electro-acupuncture on ovarian expression of α (1)- and β (2)-adrenoceptors, and p75 neurotrophin receptors in rats with steroid-induced polycystic ovaries
Authors: Manni Luigi , Lundeberg Thomas , Holmäng Agneta , Aloe Luigi , Stener-Victorin Elisabet
Published: June 2005

Background

Estradiol valerate (EV)-induced polycystic ovaries (PCO) in rats is associated with an increase in ovarian sympathetic outflow. Low-frequency (2 Hz) electro-acupuncture (EA) has been shown to modulate sympathetic markers as well as ovarian blood flow as a reflex response via the ovarian sympathetic nerves, in rats with EV-induced PCO.

Methods

In the present study, we further tested the hypothesis that repeated 2 Hz EA treatments modulate ovarian sympathetic outflow in rats with PCO, induced by a single i.m. injection of EV, by investigating the mRNA expression, the amount and distribution of proteins of α1a-, α1b-, α1d-, and β2-adrenoceptors (ARs), as well as the low-affinity neurotrophin receptor (p75NTR).

Results

It was found that EV injection results in significantly higher mRNA expression of ovarian α1b- and α1d-AR in PCO rats compared to control rats. The p75NTR and β2-ARs mRNA expression were unchanged in the PCO ovary. Low-frequency EA resulted in a significantly lower expression of β2-ARs mRNA expression in PCO rats. The p75NTR mRNA was unaffected in both PCO and control rats. PCO ovaries displayed significantly higher amount of protein of α1a-, α1b- and α1d-ARs, and of p75NTR, compared to control rats, that were all counteracted by repeated low-frequency EA treatments, except for α1b-AR.

Conclusion

The present study shows that EA normalizes most of the EV-induced changes in ovarian ARs. Furthermore, EA was able to prevent the EV-induced up regulation of p75NTR, probably by normalizing the sympathetic ovarian response to NGF action. Our data indicate a possible role of EA in the regulation of ovarian responsiveness to sympathetic inputs and depict a possible complementary therapeutic approach to overcoming sympathetic-related anovulation in women with PCOS.
Transforming growth factor beta-1 decreases the yield of the second meiotic division of rat pachytene spermatocytes in vitro
Authors: Damestoy Anne , Perrard Marie-Hélène , Vigier Michèle , Sabido Odile , Durand Philippe
Published: June 2005

Background

TGF beta and its receptors are present in both germ cells and somatic cells of the male gonad. However, knock-out strategies for studying spermatogenesis regulation by TGF beta have been disappointing since TGF beta-or TGF beta receptor-null mice do not survive longer than a few weeks.

Methods

In the present study, we addressed the role of TGF beta-1 on the completion of meiosis by rat pachytene spermatocytes (PS) cocultured with Sertoli cells. Identification and counting of meiotic cells were performed by cytology and cytometry.

Results

Under our culture conditions, some PS differentiated into round spermatids (RS). When TGF beta-1 was added to the culture medium, neither the number of PS or of secondary spermatocytes nor the half-life of RS was modified by the factor. By contrast, the number of RS and the amount of TP1 mRNA were lower in TGF beta-1-treated cultures than in control cultures. Very few metaphase I cells were ever observed both in control and TGF beta-1-treated wells. Higher numbers of metaphase II were present and their number was enhanced by TGF beta-1 treatment. A TGF beta-like bioactivity was detected in control culture media, the concentration of which increased with the time of culture.

Conclusion

These results indicate that TGF beta-1 did not change greatly, if any, the yield of the first meiotic division but likely enhanced a bottleneck at the level of metaphase II. Taken together, our results suggest strongly that TGF beta participates in an auto/paracrine pathway of regulation of the meiotic differentiation of rat spermatocytes.
Destructive effects of murine arthritogenic antibodies to type II collagen on cartilage explants in vitro
Authors: Crombie Duncan E , Turer Muhammed , Zuasti Beltzane Biurrun , Wood Bayden , McNaughton Don , Nandakumar Kutty Selva , Holmdahl Rikard , Van Damme Marie-Paule , Rowley Merrill J
Published: June 2005

Certain monoclonal antibodies (mAbs) to type II collagen (CII) induce arthritis in vivo after passive transfer and have adverse effects on chondrocyte cultures and inhibit self assembly of collagen fibrils in vitro. We have examined whether such mAbs have detrimental effects on pre-existing cartilage. Bovine cartilage explants were cultured over 21 days in the presence of two arthritogenic mAbs to CII (CIIC1 or M2139), a non-arthritogenic mAb to CII (CIIF4) or a control mAb (GAD6). Penetration of cartilage by mAb was determined by immunofluorescence on frozen sections and correlated with changes to the extracellular matrix and chondrocytes by morphometric analysis of sections stained with toluidine blue. The effects of mAbs on matrix components were examined by Fourier transform infrared microspectroscopy (FTIRM). A possible role of Fc-binding was investigated using F(ab)2 from CIIC1. All three mAbs to CII penetrated the cartilage explants and CIIC1 and M2139, but not CIIF4, had adverse effects that included proteoglycan loss correlating with mAb penetration, the later development in cultures of an abnormal superficial cellular layer, and an increased proportion of empty chondrons. FTIRM showed depletion and denaturation of CII at the explant surface in the presence of CIIC1 or M2139, which paralleled proteoglycan loss. The effects of F(ab)2 were greater than those of intact CIIC1. Our results indicate that mAbs to CII can adversely affect preformed cartilage, and that the specific epitope on CII recognised by the mAb determines both arthritogenicity in vivo and adverse effects in vitro. We conclude that antibodies to CII can have pathogenic effects that are independent of inflammatory mediators or Fc-binding.
Anticancer properties of propofol-docosahexaenoate and propofol-eicosapentaenoate on breast cancer cells
Authors: Siddiqui Rafat A , Zerouga Mustapha , Wu Min , Castillo Alicia , Harvey Kevin , Zaloga Gary P , Stillwell William
Published: June 2005

Introduction

Epidemiological evidence strongly links fish oil, which is rich in docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), with low incidences of several types of cancer. The inhibitory effects of omega-3 polyunsaturated fatty acids on cancer development and progression are supported by studies with cultured cells and animal models. Propofol (2,6-diisopropylphenol) is the most extensively used general anesthetic–sedative agent employed today and is nontoxic to humans at high levels (50 μg/ml). Clinically relevant concentrations of propofol (3 to 8 μg/ml; 20 to 50 μM) have also been reported to have anticancer activities. The present study describes the synthesis, purification, characterization and evaluation of two novel anticancer conjugates, propofol-docosahexaenoate (propofol-DHA) and propofol-eicosapentaenoate (propofol-EPA).

Methods

The conjugates linking an omega-3 fatty acid, either DHA or EPA, with propofol were synthesized and tested for their effects on migration, adhesion and apoptosis on MDA-MB-231 breast cancer cells.

Results

At low concentrations (25 μM), DHA, EPA or propofol alone or in combination had minimal effect on cell adhesion to vitronectin, cell migration against serum and the induction of apoptosis (only 5 to 15% of the cells became apoptotic). In contrast, the propofol-DHA or propofol-EPA conjugates significantly inhibited cell adhesion (15 to 30%) and migration (about 50%) and induced apoptosis (about 40%) in breast cancer cells.

Conclusion

These results suggest that the novel propofol-DHA and propofol-EPA conjugates reported here may be useful for the treatment of breast cancer.
Obesity promotes 7,12-dimethylbenz(a)anthracene-induced mammary tumor development in female zucker rats
Authors: Hakkak Reza , Holley Andy W , MacLeod Stewart L , Simpson Pippa M , Fuchs George J , Jo Chan Hee , Kieber-Emmons Thomas , Korourian Soheila
Published: June 2005

Introduction

High body mass index has been associated with increased risk for various cancers, including breast cancer. Here we describe studies using 7,12-dimethylbenz(a)anthracene (DMBA) to investigate the role of obesity in DMBA-induced mammary tumor susceptibility in the female Zucker rat (fa/fa), which is the most widely used rat model of genetic obesity.

Method

Fifty-day-old female obese (n = 25) and lean (n = 28) Zucker rats were orally gavaged with 65 mg/kg DMBA. Rats were weighed and palpated twice weekly for detection of mammary tumors. Rats were killed 139 days after DMBA treatment.

Results

The first mammary tumor was detected in the obese group at 49 days after DMBA treatment, as compared with 86 days in the lean group (P < 0.001). The median tumor-free time was significantly lower in the obese group (P < 0.001). Using the days after DMBA treatment at which 25% of the rats had developed mammary tumors as the marker of tumor latency, the obese group had a significantly shorter latency period (66 days) than did the lean group (118 days). At the end of the study, obese rats had developed a significantly (P < 0.001) greater mammary tumor incidence (68% versus 32%) compared with the lean group. The tumor histology of the mammary tumors revealed that obesity was associated with a significant (P < 0.05) increase in the number of rats with at least one invasive ductal and lobular carcinoma compared with lean rats.

Conclusion

Our results indicate that obesity increases the susceptibility of female Zucker rats to DMBA-induced mammary tumors, further supporting the hypothesis that obesity and some of its mediators play a significant role in carcinogenesis.
Relating examinations to the Common European Framework: a manual
Authors: Figueras Neus , North Brian , Takala Sauli , Verhelst Norman , Van Avermaet Piet
Published: June 2005

This article deals with the linking of examinations to the Common European Framework of Reference (CEFR). Following the rapid adoption of the CEFR by the Council of Europe and the European Union as well as many national and local actors, there have been calls for guidance on how examinations could be made more transparent by means of the CEFR, especially by using its calibrated scales as a tool. The Council of Europe has recently produced a preliminary pilot Manual, which presents a procedure for doing this. The article describes the political and educational context of this work and presents the main procedures proposed in the Manual. Since the Manual is a preliminary document for discussion and feedback, the authors of the Manual join the discussion by presenting some critical reflections of their own. The article concludes by outlining two scenarios: one which predicts positive developments and the other which foresees less desirable consequences.
Limitations of the Common European Framework for developing comparable examinations and tests
Authors: Weir Cyril J.
Published: June 2005

The Common European Framework of Reference (CEFR) posits six levels of proficiency and defines these largely in relation to empirically derived difficulty estimates based on stakeholder perceptions of what language functions expressed by ‘Can-do’ statements can be successfully performed at each level. Though also containing much valuable information on language proficiency and advice for practitioners, in its present form the CEFR is not sufficiently comprehensive, coherent or transparent for uncritical use in language testing. First, the descriptor scales take insufficient account of how variation in terms of contextual parameters may affect performances by raising or lowering the actual difficulty level of carrying out the target ‘Can-do’ statement. In addition, a test’s theory-based validity - a function of the processing involved in carrying out these ‘Can-do’ statements - must also be addressed by any specification on which a test is based. Failure to explicate such context and theory-based validity parameters - i.e., to comprehensively define the construct to be tested - vitiates current attempts to use the CEFR as the basis for developing comparable test forms within and across languages and levels, and hampers attempts to link separate assessments, particularly through social moderation.
The development of a suite of computer-based diagnostic tests based on the Common European Framework
Authors: Alderson J. Charles , Huhta Ari
Published: June 2005

DIALANG is an on-line language assessment system, which contains tests in 14 European languages and is based on the Common European Framework of Reference (CEFR). It is the first major testing system that is oriented towards diagnosing language skills and providing feedback to users rather than certifying their proficiency. This article describes the contents of Version 1 of DIALANG and the way in which the system works. This is followed by an account of the development of DIALANG tests and of the pilot testing and standard setting procedures. The results of the first analyses of items and self-assessment statements, and of the standard setting procedures, are reported. The article focuses on the results for English, but findings for some other languages are also touched upon.
Language testing in the military: problems, politics and progress
Authors: Green Rita , Wall Dianne
Published: June 2005

There appears to be little literature available -either descriptive or research-related - on language testing in the military. This form of specific purposes assessment affects both military personnel and civilians working within the military structure in terms of posting, promotion and remuneration, and it could be argued that it has serious social consequences if not carried out professionally and to the highest standard. This article provides a general overview of the language testing that is carried out by military teams in Central and Eastern Europe, using the findings of three surveys conducted with teams in this region. It explores the design problems the teams have had to deal with, the political issues that influence the work they do, and the progress they have been able to make over recent years. The article concludes with an attempt to link these findings to broader issues in the assessment of English for Specific Purposes.
Alterations in protein kinase A signalling and cleft palate: a review
Authors: Reddy Chada S
Published: June 2005

Cyclic AMP is an important second messenger mediating the actions of many hormones and other ligands in a variety of cells. Cells of the developing organism are no exception. Once generated, it releases the catalytic subunit of protein kinase A (PKA) from the inhibitory influence of its regulatory subunit, which then migrates into the nucleus to phosphorylate and enhance the binding of relevant transcription factors to the promoter element CRE of genes involved in above cellular responses. This review summarizes the available data on the essential role of this pathway in embryonic development as well as the functionality, ontogeny and consequences of genetic and chemical disruption of this pathway in the developing orofacial structures, especially the secondary palate as influenced by the mycotoxin, secalonic acid D.
A critique of the use of hormesis in risk assessment
Authors: Kitchin Kirk T , Drane J Wanzer
Published: June 2005

There are severe problems and limitations with the use of hormesis as the principal dose-response default assumption in risk assessment. These problems and limitations include: (a) unknown prevalence of hormetic doseresponse curves; (b) random chance occurrence of hormesis and the shortage of data on the repeatability of hormesis; (c) unknown degree of generalizability of hormesis; (d) there are dose-response curves that are not hormetic, therefore hormesis cannot be universally generalized; (e) problems of post hoc rather than a priori hypothesis testing; (f) a possible large problem of ‘false positive’ hormetic data sets which have not been extensively replicated; (g) the ‘mechanism of hormesis’ is not understood at a rigorous scientific level; (h) in some cases hormesis may merely be the overall sum of many different mechanisms and many different dose-response curves - some beneficial and some toxic. For all of these reasons, hormesis should not now be used as the principal dose-response default assumption in risk assessment. At this point, it appears that hormesis is a long way away from common scientific acceptance and wide utility in biomedicine and use as the principal default assumption in a risk assessment process charged with ensuring public health protection.
Can hormesis be a default for dose-response?
Authors: Callahan Barbara G
Published: June 2005

Since the 1920s, interest in hormesis has peaked and ebbed. Hormesis had been a forgotten theory until recent investigation by Dr Ed Calabrese at the University of Massachusetts, along with others, resurrected it from obscurity. This renewed interest is demonstrated by recent articles in prestigious scientific journals such as Nature and Science as well as the popular press (Discovery, US News and World Report and newspapers such as the Boston Globe). Currently, a strong interest in this theory of dose-response (which predicts contrasting effects at low versus high doses) exists and is explored in this issue.
An epidemiological study of poisoning cases reported to the National Poisons Information Centre, All India Institute of Medical Sciences, New Delhi
Authors: Srivastava Amita , Peshin Sharda Shah , Kaleekal Thomas , Gupta Suresh Kumar
Published: June 2005

A retrospective analysis of poisoning calls received by the National Poisons Information Centre showed a total of 2719 calls over a period of three years (April 1999-March 2002). The queries were made on poisoning management (92%) and information (8%) about various products and functioning of the centre. The data were analysed with respect to age, sex, mode and type of poisoning. The agents belonged to various groups: household products, agricultural pesticides, industrial chemicals, drugs, plants, animal bites and stings, miscellaneous and unknown groups respectively. The age ranged from less than 1 to 70 years, with the highest incidence in the range of 14-40 years, with males (57%) outnumbering females (43%). The most common mode of poisoning was suicidal (53%), followed by accidental (47%). The route of exposure was mainly oral (88%). Dermal (5%), inhalation and ocular exposure contributed 7% to the total. The highest incidence of poisoning was due to household agents (44.1%) followed by drugs (18.8%), agricultural pesticides (12.8%), industrial chemicals (8.9%), animals bites and stings (4.7%), plants (1.7%), unknown (2.9%) and miscellaneous groups (5.6%). Household products mainly comprised of pyrethroids, rodenticides, carbamates, phenyl, detergents, corrosives etc. Drugs implicated included benzodiazepines, anticonvulsants, analgesics, antihistamines, tricyclic antidepressants, thyroid hormones and oral contraceptives. Among the agricultural pesticides, aluminium phosphide was the most commonly consumed followed by organochlorines, organophosphates, ethylene dibromide, herbicides and fungicides. Copper sulphate and nitrobenzene were common among industrial chemicals. The bites and stings group comprised of snake bites, scorpion, wasp and bee stings. Poisoning due to plants was low, but datura was the most commonly ingested. An alarming feature of the study was the high incidence of poisoning in children (36.5%). The age ranged from less than 1 to 18 years and the most vulnerable age group included children from less than 1 year to 6 years. Accidental mode was the most common (79.7%). Intentional attempts were also noticed (20.2%) in the age group above 12 years. The present data may not give an exact picture of the incidence of poisoning in India, but represents a trend in our country. The Poisons Information Centre plays a vital role in providing timely management guidelines including the supply of necessary antidotes from the recently established National Antidote Bank, thereby helping to save precious lives.
Cardioprotective effect of pentacyclic triterpene, lupeol and its ester on cyclophosphamide-induced oxidative stress
Authors: Sudharsan P T , Mythili Y , Selvakumar E , Varalakshmi P
Published: June 2005

Cyclophosphamide (CP), an alkylating agent widely used in cancer chemotherapy, causes fatal cardiotoxicity. In the present study, lupeol, a pentacyclic triterpene, isolated from Crataeva nurvala stem bark and its ester, lupeol linoleate were investigated for their possible cardioprotective effects against CP-induced toxicity. Male albino rats of Wistar strain were injected with a single dose of CP (200 mg/kg body weight, ip). In CP-administered rats, activities of lactate dehydrogenase and creatine phosphokinase were elevated in serum with a concomitant decline in their activities in the cardiac tissue. Significant increases (P B < 0.001) in the levels of lipid peroxides and a decrease (P B < 0.001) in the levels of enzymic (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase and glutathione-s-transferase) and nonenzymic (reduced glutathione, vitamin C and vitamin E) antioxidants in the heart were also observed. The cardioprotective effects of lupeol (50 mg/kg body weight for 10 days orally) and its ester, lupeol linoleate (50 mg/kg body weight for 10 days orally) were evident from the significant reversal of the above alterations induced by CP. These observations highlight the antioxidant property of triterpenes and their cytoprotective action against CPinduced cardiotoxicity.
Acute intoxication with doxazosin
Authors: Satar Salim , Sebe Ahmet , Avci Akkan , Yesilagac Hasan , Gokel Yuksel
Published: June 2005

Experience with overdosage and toxicity with the alphaadrenoreceptor antagonists remains very limited in the literature. In this paper, the second case in the literature with doxazosin overdosage is reported. Supportive treatment was given to the patient and the patient was discharged 48 hours after admission to the emergency department.
Extremely sensitive biomarker of acute organophosphorus insecticide exposure
Authors: Fujikawa Yasuhiro , Satoh Tetsuo , Suganuma Akiyoshi , Suzuki Satoshi , Niikura Yasuko , Yui Shinobu , Yamaura Yoshiro
Published: June 2005

Egasyn-βglucuronidase complex is located at the luminal site of liver microsomal endoplasmic reticulum. When organophosphorus insecticides (OP) are incorporated into the liver microsomes, they become tightly bound to egasyn, a carboxylesterase isozyme, and subsequently, β-glucuronidase (BG) is dissociated and released into blood. Consequently, the increase in plasma BG activity becomes a good biomarker of OP exposure. Thus, the single administration of EPN (O-ethyl O-p-nitrophenylphenylphosphonothioate), acephate and chlorpyrifos increased plasma BG activity in approximately 100-fold the control level in rats. The increase in plasma BG activity after OP exposure is a much more sensitive biomarker of acute OP exposure than acetylcholinesterase (AChE) inhibition.
Study of Paclitaxel, Etoposide, and Cisplatin Chemotherapy Combined With Twice-Daily Thoracic Radiotherapy for Patients With Limited-Stage Small-Cell Lung Cancer: A Radiation Therapy Oncology Group 9609 Phase II Study
Authors: Ettinger David S. , Berkey Brian A. , Abrams Ross A. , Fontanesi James , Machtay Mitchell , Duncan Philip J. , Curran Walter J. , Movsas Benjamin , Byhardt Roger W.
Published: June 2005

Purpose

To determine the response rate, progression-free survival and overall survival, and toxicity of paclitaxel, etoposide, and cisplatin combined with accelerated hyperfractionated thoracic radiotherapy in patients with limited-disease (LD) small-cell lung cancer (SCLC).

Patients and Methods

LD-SCLC patients with measurable disease, Karnofsky performance score of ≥ 70, and adequate organ function who were previously untreated were eligible for the study. Treatment was as follows. In cycle 1 of chemotherapy, concurrent thoracic radiation therapy was administered. In cycles 2 to 4, chemotherapy was administered alone. In cycle 1, chemotherapy consisted of paclitaxel 135 mg/m2 intravenous over 3 hours on day 1, etoposide 60 mg/m2 intravenous on day 1 and 80 mg/m2 orally on days 2 and 3, and cisplatin 60 mg/m2 intravenous on day 1. In cycles 2 to 4, the paclitaxel dose was increased to 175 mg/m2, with the etoposide and cisplatin doses remaining the same as in cycle 1. The thoracic radiation therapy consisted of 1.5 Gy in 30 fractions (total dose, 45 Gy) administered 5 days a week for 3 weeks.

Results

Fifty-five patients were enrolled onto the study, and 53 were assessable. The major toxicities included grade 3 and 4 acute neutropenia (32% and 43%, respectively) and grade 3 and 4 esophagitis (32% and 4%, respectively). Two patients died as a result of therapy (one died of acute respiratory distress syndrome, and one died of sepsis). There was one late fatal pulmonary toxicity. The median survival time was 24.7 months. The 2-year survival rate was 54.7%. The median progression-free survival time was 13 months, with a 2-year progression-free survival rate of 26.4%.

Conclusion

Although this therapeutic regimen is effective in the treatment of patients with LD-SCLC, it is unlikely that the three-drug combination with thoracic radiation therapy will improve the survival times compared with the etoposide plus cisplatin chemotherapy regimen with thoracic radiation therapy in LD-SCLC patients.
Effect of Individual Psychological Intervention in Chinese Women With Gynecologic Malignancy: A Randomized Controlled Trial
Authors: Chan Y.M. , Lee Peter W.H. , Fong Daniel Y.T. , Fung Amy S.M. , Wu Lina Y.F. , Choi Alice Y.Y. , Ng T.Y. , Ngan Hextan Y.S. , Wong L.C.
Published: June 2005

Purpose

To evaluate the effectiveness of psychological intervention in the care of cancer patients and to determine whether routine use of individual psychological therapies is indicated.

Patients and Methods

Patients with newly diagnosed gynecologic malignancies from August 1999 to November 2000 were recruited and randomly assigned to either a control group receiving routine medical care or to an intervention group receiving individual psychotherapy. A set of fixed-choice, self-report questionnaires assessing the patients' psychological status, quality of life, and their perceptions related to the medical consultations was completed at recruitment and then every 3 months for 18 months. Data analysis was performed according to the intention-to-treat principle by fitting the data into a linear mixed-effects model. Multivariable analyses were performed to examine the effects of confounding factors.

Results

One hundred fifty-five patients participated in the trial. There were no statistically significant differences between the two groups at baseline. There was a trend toward better quality of life and functional status and also improvement of the symptoms over time for both groups. No differences were found between the groups in the scores measured by any of the instruments at baseline and at any time points after the cancer diagnosis. Psychological intervention had no significant effects on the psychosocial parameters.

Conclusion

Routine use of psychological therapies as given in our format has no significant effect on the patients' quality of life and psychological status.
Phase I and Pharmacokinetic Study of LY293111, an Orally Bioavailable LTB4 Receptor Antagonist, in Patients With Advanced Solid Tumors
Authors: Schwartz Gary K. , Weitzman Aaron , O'Reilly Eileen , Brail Les , de Alwis Dinesh P. , Cleverly Ann , Barile-Thiem Barbara , Vinciguerra Vincent , Budman Daniel R.
Published: June 2005

Purpose

LY293111, a novel diaryl ether carboxylic acid derivative, is a potent and selective inhibitor of the lipoxygenase pathway either directly through 5′-lipoxygenase or via antagonism of the leukotriene B4 (LTB4) receptor. More recently it has been determined to have peroxisome proliferator activated receptor-gamma agonist (PPARγ) activity. LY293111 has antineoplastic activity in a variety of preclinical models. The tolerability and pharmacokinetics of LY293111 administered continuously, by mouth, BID for repeat cycles of 21 days was evaluated.

Patients and Methods

Thirty-eight patients with advanced solid tumors were treated at five dose levels (200 to 800 mg BID) for a total of 102 cycles.

Results

The most common toxicity was diarrhea (76%). One patient at 600 mg BID (n = 11) and two at 800 mg BID (n = 8), experienced dose-limiting grade 3 diarrhea. Dose reductions and/or delays were infrequent. Increases in steady-state maximum plasma concentration (Cmax,ss) and area under the steady-state plasma concentration time curve 0 to 12 hours (AUCτ,ss) on day 8 could be considered to be dose-proportional over the four-fold-dose range. Interpatient variability in Cmax,ss and AUCτ,ss was estimated to be 65% and 71% respectively. There was a small increase in AUC (1.37; 90% CI, 0.85 to 2.21) between single and multiple doses. Two patients with progressive chondrosarcoma and melanoma had stable disease lasting approximately 336 and 168 days, respectively.

Conclusion

LY293111 can be administered safely by continuous oral therapy with mild toxicities. Diarrhea is dose-limiting. The recommended phase II dose will be 600 mg BID. The steady-state concentrations in humans exceed relevant levels observed in preclinical models.
Thalidomide Downregulates Angiogenic Genes in Bone Marrow Endothelial Cells of Patients With Active Multiple Myeloma
Authors: Vacca Angelo , Scavelli Claudio , Montefusco Vittorio , Di Pietro Giulia , Neri Antonino , Mattioli Michela , Bicciato Silvio , Nico Beatrice , Ribatti Domenico , Dammacco Franco , Corradini Paolo
Published: June 2005

Purpose

To study the antiangiogenic effect of thalidomide.

Patients and Methods

The expression of key angiogenic genes was studied in bone marrow endothelial cells (ECs) of patients with active and nonactive multiple myeloma (MM), monoclonal gammopathies unattributed/unassociated (MG[u]), diffuse large B-cell non-Hodgkin's lymphoma, in a Kaposi's sarcoma (KS) cell line, and in healthy human umbilical vein ECs (HUVECs) following exposure to therapeutic doses of thalidomide.

Results

Thalidomide markedly downregulates the genes in a dose-dependent fashion in active MMECs and KS cell line, but upregulates them or is ineffective in nonactive MMECs, MG(u)ECs, NHL-ECs, and in HUVECs. Secretion of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and hepatocyte growth factor also diminishes according to the dose in culture conditioned media (CM) of active MMECs and KS, whereas it does not change in the other CM.

Conclusion

Inhibition by thalidomide is probably confined to the genes of active MMECs and KS. This would account for its higher efficacy in these diseases.
Phase III Randomized Trial of FOLFIRI Versus FOLFOX4 in the Treatment of Advanced Colorectal Cancer: A Multicenter Study of the Gruppo Oncologico Dell’Italia Meridionale
Authors: Colucci Giuseppe , Gebbia Vittorio , Paoletti Giancarlo , Giuliani Francesco , Caruso Michele , Gebbia Nicola , Cartenì Giacomo , Agostara Biagio , Pezzella Giuseppe , Manzione Luigi , Borsellino Nicola , Misino Andrea , Romito Sante , Durini Ernesto , Cordio Stefano , Di Seri Marisa , Lopez Massimo , Maiello Evaristo
Published: June 2005

Purpose

We performed this phase III study to compare the irinotecan, leucovorin (LV), and fluorouracil (FU) regimen (FOLFIRI) versus the oxaliplatin, LV, and FU regimen (FOLFOX4) in previously untreated patients with advanced colorectal cancer.

Patients and Methods

A total of 360 chemotherapy-naive patients were randomly assigned to receive, every 2 weeks, either arm A (FOLFIRI: irinotecan 180 mg/m2 on day 1 with LV 100 mg/m2 administered as a 2-hour infusion before FU 400 mg/m2 administered as an intravenous bolus injection, and FU 600 mg/m2 as a 22-hour infusion immediately after FU bolus injection on days 1 and 2 [LV5FU2]) or arm B (FOLFOX4: oxaliplatin 85 mg/m2 on day 1 with LV5FU2 regimen).

Results

One hundred sixty-four and 172 patients were assessable in arm A and B, respectively. Overall response rates (ORR) were 31% in arm A (95% CI, 24.6% to 38.3%) and 34% in arm B (95% CI, 27.2% to 41.5%; P = .60). In both arms A and B, median time to progression (TTP; 7 v 7 months, respectively), duration of response (9 v 10 months, respectively), and overall survival (OS; 14 v 15 months, respectively) were similar, without any statistically significant difference. Toxicity was mild in both groups: alopecia and gastrointestinal disturbances were the most common toxicities in arm A; thrombocytopenia and neurosensorial were the most common toxicities in arm B. Grade 3 to 4 toxicities were uncommon in both arms, and no statistical significant difference was observed.

Conclusion

There is no difference in ORR, TTP, and OS for patients treated with the FOLFIRI or FOLFOX4 regimen. Both therapies seemed effective as first-line treatment in these patients. The difference between these two combination therapies is mainly in the toxicity profile.
Phase II and Tumor Pharmacodynamic Study of Gefitinib in Patients with Advanced Breast Cancer
Authors: Baselga José , Albanell Joan , Ruiz Amparo , Lluch Ana , Gascón Pere , Guillém Vicente , González Sonia , Sauleda Silvia , Marimón Irene , Tabernero Josep M. , Koehler Maria T. , Rojo Federico
Published: June 2005

Purpose

To evaluate the antitumor activity and pharmacodynamic/biologic effect of gefitinib 500 mg/day monotherapy in patients with previously treated, advanced breast cancer.

Methods

In this phase II multicenter trial, the primary objective was assessment of the tumor response rate with gefitinib; secondary objectives included analysis of the pharmacodynamic and biologic profiles in healthy and tumor tissue.

Results

Of 31 assessable patients, 12 (38.7%) had stable disease, including 3 (9.7%) with recurrent breast cancer that stabilized for ≥ 6 months. No complete or partial responses were observed. Pretreatment tumor samples were available in all patients. In addition, paired baseline and on-treatment (day 28) assessable skin and tumor biopsies were available in 27 and 16 patients, respectively. Sequential immunohistochemical studies in skin and tumor biopsies demonstrated complete inhibition of epidermal growth factor receptor (EGFR) phosphorylation in both healthy and malignant tissues. The downstream consequences of receptor blockade were distinct in skin and tumor samples: while phosphorylation of mitogen-activated protein kinase was inhibited in both tissues, gefitinib treatment induced p27 and a decrease in Ki67 in skin but not in tumors. Furthermore, gefitinib did not inhibit the activated form of Akt in the tumors.

Conclusion

This study demonstrates a good correlation between the degree of inhibition of EGFR in skin and in breast tumors. The lack of significant clinical activity of gefitinib in our study population is not due to lack of receptor inhibition in these tumors but rather to lack of EGFR dependence in the tested population.
Adjuvant Cisplatin Plus Methotrexate Versus Methotrexate, Vinblastine, Epirubicin, and Cisplatin in Locally Advanced Bladder Cancer: Results of a Randomized, Multicenter, Phase III Trial (AUO-AB 05/95)
Authors: Lehmann Jan , Retz Margitta , Wiemers Christina , Beck Joachim , Thüroff Joachim , Weining Christoph , Albers Peter , Frohneberg Detlef , Becker Tanja , Funke Peter-Jörg , Walz Peter , Langbein Sigrun , Reiher Frank , Schiller Matthias , Miller Kurt , Roth Stephan , Kälble Tilman , Sternberg Donald , Wellek Stefan , Stöckle Michael
Published: June 2005

Purpose

Radical cystectomy as standard treatment of muscle-invasive urothelial carcinoma of the urinary bladder cures less than 50% of patients with locally advanced bladder cancer. We compared two adjuvant combination chemotherapies in patients with stage pT3a-4a and/or pathologic node-positive transitional-cell carcinoma of the bladder after radical cystectomy.

Patients and Methods

A total of 327 patients were randomly assigned to either adjuvant systemic chemotherapy with three cycles of cisplatin 70 mg/qm2 on day 1 and methotrexate 40 mg/qm2 on days 8 and 15 of a 21-day cycle (CM) or three cycles of methotrexate 30 mg/qm2 on days 1, 15, and 22, vinblastine 3 mg/qm2 on days 2, 15, and 22, epirubicin 45 mg/qm2 on day 2, and cisplatin 70 mg/qm2 on day 2 of a 28-day cycle (M-VEC).

Results

The hazard ratio for progression-free survival as the primary end point was 1.13 (90% CI, 0.86 to 1.48) for 163 CM patients compared with 164 M-VEC patients whose right-hand limit remained below the upper bound compatible with the noninferiority hypothesis (α = .0403). The 5-year progression-free, tumor-specific, and overall survival rates (point estimates ± SE) for CM versus M-VEC were 46.3% ± 4.6% v 48.8% ± 4.5%, 52.0% ± 4.6% v 52.3% ± 4.8%, and 46.1% ± 4.3% v 45.1% ± 4.6%, respectively. WHO grade 3 and 4 leukopenia occurred in 7.0% of patients treated with CM and 22.2% of patients treated with M-VEC (P < .0001).

Conclusion

CM cannot be considered inferior to M-VEC with regard to progression-free survival of patients with locally advanced bladder cancer after radical cystectomy. Moreover, patients receiving adjuvant CM combination therapy experienced significantly less grade 3 and 4 leukopenia than patients treated with M-VEC.
Zebrafish Lmx1b.1 and Lmx1b.2 are required for maintenance of the isthmic organizer
Authors: O'Hara F. Patrick , Beck Ernestine , Barr Lauren K. , Wong Lily L. , Kessler Daniel S. , Riddle Robert D.
Published: June 2005

The mesencephalic and metencephalic region (MMR) of the vertebrate central nervous system develops in response to signals produced by the isthmic organizer (IsO). We have previously reported that the LIM homeobox transcription factor Lmx1b is expressed within the chick IsO, where it is sufficient to maintain expression of the secreted factor wnt1. In this paper, we show that zebrafish express two Lmx1b orthologs, lmx1b.1 and lmx1b.2, in the rostral IsO, and demonstrate that these genes are necessary for key aspects of MMR development. Simultaneous knockdown of Lmx1b.1 and Lmx1b.2 using morpholino antisense oligos results in a loss of wnt1, wnt3a, wnt10b, pax8 and fgf8 expression at the IsO, leading ultimately to programmed cell death and the loss of the isthmic constriction and cerebellum. Single morpholino knockdown of either Lmx1b.1 or Lmx1b.2 has no discernible effect on MMR development. Maintenance of lmx1b.1 and lmx1b.2 expression at the isthmus requires the function of no isthmus/pax2.1, as well as Fgf signaling. Transient misexpression of Lmx1b.1 or Lmx1b.2 during early MMR development induces ectopic wnt1 and fgf8 expression in the MMR, as well as throughout much of the embryo. We propose that Lmx1b.1- and Lmx1b.2-mediated regulation of wnt1, wnt3a, wnt10b, pax8and fgf8 maintains cell survival in the isthmocerebellar region.
Measurement of Sulfur Dioxide with the Differential Optical Absorption Technique Combined with Fourier Transformation
Authors: Axelsson L. , Lauber A.
Published: June 2005

The concentration of sulfur dioxide has been measured in the ultraviolet spectral range with a combination of the differential optical absorption technique and Fourier transformation. Measurements have been made with a pathlength of two meters and a measuring time of one minute. Sulfur dioxide levels of less than 0.1 ppm (volume) were assessed with a measurement uncertainty of ±0.03 ppm (volume). This method also shows good robustness against displacements in the wavelength range of the incoming absorption spectrum.
Application of Dynamical Analysis Techniques in the Extraction of Compound-Specific Information from Fourier Transform Infrared Interferograms
Authors: Carpenter Scott E. , Small Gary W.
Published: June 2005

An automated compound-detection procedure is described that is based on the application of dynamical analysis techniques to digitally filtered Fourier transform infrared interferogram data. With the use of benzene as a test analyte, surface-of-section maps are computed from the filtered data. This calculation is resistant to phase variation in the interferograms and serves to remove the oscillating component of the filtered signal. Information regarding the overall shape or profile of the signal is enhanced, thereby resulting in an improved sensitivity for distinguishing analyte information from that due to interferences. Data vectors constructed from the surface-of-section maps are examined by use of principal component analysis. Linear discriminant analysis is then used to implement an automated algorithm for detecting benzene in the presence of nitrobenzene. When tested with data not included in the discriminant development computations, the computed linear discriminants are shown to perform with a detection accuracy of greater than 99%.
Simple Fiber-Optic-Based Interface to Facilitate Spectroscopic Measurements in Supercritical Solvents
Authors: Zagrobelny Joann , Li Ming , Wang Run , Betts Thomas A. , Bright Frank V.
Published: June 2005

A new fiber-optic-based interface is described to facilitate fluorescence measurements in supercritical solvents. Steady-state and time-resolved measurements are possible, and assembly/disassembly is significantly easier compared to that required for traditional high-pressure optical cell designs.
Analysis of the Coated Interface Using Fourier Transform Infrared Microspectroscopy
Authors: Nishioka Toshikatsu , Nakano Tatsuhiko , Teramae Norio
Published: June 2005

Fourier transform infrared microspectroscopy was applied in order to analyze the interaction of the coated interface between two different polymers. The samples investigated were prepared by coating urethane paint on an ethylene-acrylic acid copolymer (EAA) and on an ethylene-ethyl acrylate copolymer whose ethylester group had been partially hydrolyzed (EAA/EEA). It was demonstrated that a mixed phase was formed along the coated interface between the urethane paint and the EAA and between the paint and the EAA/EEA. The interaction between molecules of the polyurethane and the EAA was observed.
Fast Scanning Hadamard Spectrophotometer
Authors: Poppi Ronei J. , Vazquez Pedro A. M. , Pasquini Celio
Published: June 2005

A simple, low-cost, multiplexed Hadamard-type spectrophotometer based on a spinning disk containing 63 separated masks has been constructed to obtain spectral data in time intervals down to 50 ms. Each mask contains 63 resolution elements. Optical localization and identification of the masks were implemented in the disk to avoid misalignment problems. The control of the spectrophotometer and data acquisition was made by using a dedicated single-board microcomputer based on an 8085 CPU. The single board microcomputer sends the data, through an RS-232C interface, to an IBM-AT compatible microcomputer where the Hadamard transform is performed to recover and display the emission, transmittance, or absorbance spectrum. The instrument has been used in the visible range to obtain absorbance data for time-resolved flow injection analysis applications.
Band-Shape Analysis of the Electronic Spectra of the Schiff Bases of 5′-Deoxypyridoxal and n-Hexylamine in Cationic Micelles
Authors: Del Vado M. Angeles García , Echevarría Gerardo R. , Segura Miguel A. Vázquez , Pardo Josefa Donoso , Muñoz Francisco , Blanco Francisco García
Published: June 2005

We analyzed the UV-visible absorption spectra of the Schiff bases formed between 5′-deoxypyridoxal (DPL) and n-hexylamine (HEX) in aqueous media of various ionic strengths containing different concentrations of the cationic surfactant hexadecyltrimethylammonium bromide (CTAB). According to the results obtained, the hydrophobic chains of the surfactant interact with the hydrocarbon chain of the imine, thereby displacing the tautomeric equilibrium to the enol form. An increase in the electrolyte concentration also lowers the polarity of the environment where the Schiff base lies, thus also increasing the proportion of the enol form. The results obtained in this micellar medium suggest that the system can be used as a model for hydrophobic media.
A New Spray Chamber for Inductively Coupled Plasma Spectrometry
Authors: Wu Min , Hieftje Gary M.
Published: June 2005

A new type of spray chamber is evaluated for inductively coupled plasma emission spectrometry. The new design combines gravitational, centrifugal, turbulent and impact loss mechanisms in one apparatus to efficiently remove large droplets, increase transport efficiency and reduce memory effects. Compared with the commonly used Scott-type spray chamber, the new vertical rotary spray chamber has at least 30% higher sample-utilization efficiency, 2–3 times shorter sample clean-out time, half the cost, and simplified construction. Moreover, it offers somewhat better signal-to-background ratios, detection limits, and precision.
Application of Multivariate Analyses to NIR Spectra of Gelatinized Starch
Authors: Bertrand D. , Scotter C. N. G.
Published: June 2005

This paper describes an approach for studying collections of near-infrared spectra by using multivariate analyses. The method is illustrated with the use of two sets of spectra of gelatinized starch, recorded in the transmission mode between 650 and 1235 nm. The first set consisted of 99 spectra of partly gelatinized samples (from 24.5 to 100% gelatinization). Application of principal component analysis (PCA) made it possible to identify an outlying sample and to identify the importance of spectral variations due to the effect of scattering. Hence, it was possible to eliminate the scatter variations. From principal component regression (PCR), it was shown that the relationship between corrected spectra and gelatinization was not linear. Discriminant analysis was applied to seven classes of starch gelatinization. Only five samples out of 98 were incorrectly identified. The second set of samples was designed for studying the effect of temperature variation on the spectra of fully gelatinized starch samples. It was possible to show from PCR that the relationship between the spectra and temperature was linear. The “spectral patterns” assessed from discriminant analysis of starch gelatinization and from the PCR of temperature were compared.