bluuebunny/crossref_metadata_2025_split huggingface dataset:
Percutaneous Image-Guided Radiofrequency Ablation of Painful Metastases Involving Bone: A Multicenter Study
Authors: Goetz Matthew P. , Callstrom Matthew R. , Charboneau J. William , Farrell Michael A. , Maus Timothy P. , Welch Timothy J. , Wong Gilbert Y. , Sloan Jeff A. , Novotny Paul J. , Petersen Ivy A. , Beres Robert A. , Regge Daniele , Capanna Rodolfo , Saker Mark B. , Grönemeyer Dietrich H.W. , Gevargez Athour , Ahrar Kamran , Choti Michael A. , de Baere Thierry J. , Rubin Joseph 
Published: January 2004

Purpose Few options are available for pain relief in patients with bone metastases who fail standard treatments. We sought to determine the benefit of radiofrequency ablation (RFA) in providing pain relief for patients with refractory pain secondary to metastases involving bone. Patients and Methods Thirty-one US and 12 European patients with painful osteolytic metastases involving bone were treated with image-guided RFA using a multitip needle. Treated patients had ≥ 4/10 pain and had either failed or were poor candidates for standard treatments such as radiation or opioid analgesics. Using the Brief Pain Inventory–Short Form, worst pain intensity was the primary end point, with a 2-unit drop considered clinically significant. Results Forty-three patients were treated (median follow-up, 16 weeks). Before RFA, the mean score for worst pain was 7.9 (range, 4/10 to 10/10). Four, 12, and 24 weeks following treatment, worst pain decreased to 4.5 (P < .0001), 3.0 (P < .0001), and 1.4 (P = .0005), respectively. Ninety-five percent (41 of 43 patients) experienced a decrease in pain that was considered clinically significant. Opioid usage significantly decreased at weeks 8 and 12. Adverse events were seen in 3 patients and included (1) a second-degree skin burn at the grounding pad site, (2) transient bowel and bladder incontinence following treatment of a metastasis involving the sacrum, and (3) a fracture of the acetabulum following RFA of an acetabular lesion. Conclusion RFA of painful osteolytic metastases provides significant pain relief for cancer patients who have failed standard treatments.
Quality of Life Among Disease-Free Survivors of Rectal Cancer
Authors: Rauch Philippe , Miny Joelle , Conroy Thierry , Neyton Lionel , Guillemin Francis 
Published: January 2004

Purpose To identify factors affecting the quality of life (QoL) of disease-free survivors of rectal cancer. Patients and Methods One hundred twenty-one patients in complete remission more than 2 years after diagnosis were asked to complete three QoL questionnaires: the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30; its colorectal module, QLQ-CR38; and the Duke generic instrument. Results Patients reported less pain (P = .002) than did controls drawn from the general population. EORTC QLQ-C30 physical scores were also higher among rectal cancer survivors than in the general Norwegian or German population (P = .0005 and P = .002, respectively). Unexpectedly, stoma patients reported better social functioning than did nonstoma patients (P = .005), with less anxiety (P = .008) and higher self-esteem (P = .0002). In the present authors' experience, the QLQ-CR38 does not discriminate between these groups. Residual abdominal or pelvic pain and constipation had the most negative influence on QoL. Conclusion QoL is high among rectal cancer survivors, including stoma patients. Simultaneous use of several QoL questionnaires appears to have value in follow-up and in monitoring the effects of therapy. The impact of residual pain and constipation on long-term QoL should be considered when establishing a treatment regimen.
Prospective Multicenter Study of Axillary Nodal Staging by Positron Emission Tomography in Breast Cancer: A Report of the Staging Breast Cancer With PET Study Group
Authors: Wahl Richard L. , Siegel Barry A. , Coleman R. Edward , Gatsonis Constantine G. 
Published: January 2004

Purpose To determine the accuracy of positron emission tomography with fluorine-18–labeled 2-fluoro-2-deoxy-d-glucose (FDG-PET) in detecting axillary nodal metastases in women with primary breast cancer. Patients and Methods In this prospective multicenter study, 360 women with newly diagnosed invasive breast cancer underwent FDG-PET. Images were blindly interpreted by three experienced readers for abnormally increased axillary FDG uptake. Imaging results from 308 assessable axillae were compared with axillary node pathology. Results For detecting axillary nodal metastasis, the mean estimated area under the receiver operator curve for the three readers was 0.74 (range, 0.70 to 0.76). If at least one probably or definitely abnormal axillary focus was considered positive, the mean (and range) sensitivity, specificity, and positive and negative predictive values for PET were 61% (54% to 67%), 80% (79% to 81%), 62% (60% to 64%), and 79% (76% to 81%), respectively. False-negative axillae on PET had significantly smaller and fewer tumor-positive lymph nodes (2.7) than true-positive axillae (5.1; P < .005). Semiquantitative analysis of axillary FDG uptake showed that a nodal standardized uptake value (lean body mass) more than 1.8 had a positive predictive value of 90%, but a sensitivity of only 32%. Finding two or more intense foci of tracer uptake in the axilla was highly predictive of axillary metastasis (78% to 83% positive predictive value), albeit insensitive (27%). Conclusion FDG-PET has moderate accuracy for detecting axillary metastasis but often fails to detect axillae with small and few nodal metastases. Although highly predictive for nodal tumor involvement when multiple intense foci of tracer uptake are identified, FDG-PET is not routinely recommended for axillary staging of patients with newly diagnosed breast cancer.
Phase III Randomized Trial of Docetaxel Plus Cisplatin Versus Vindesine Plus Cisplatin in Patients With Stage IV Non-Small-Cell Lung Cancer: The Japanese Taxotere Lung Cancer Study Group
Authors: Kubota Kaoru , Watanabe Koshiro , Kunitoh Hideo , Noda Kazumasa , Ichinose Yukito , Katakami Nobuyuki , Sugiura Takahiko , Kawahara Masaaki , Yokoyama Akira , Yokota Soichiro , Yoneda Shuichi , Matsui Kaoru , Kudo Shinzo , Shibuya Masahiko , Isobe Takeshi , Segawa Yoshihiko , Nishiwaki Yutaka , Ohashi Yasuo , Niitani Hisanobu 
Published: January 2004

Purpose Few randomized trials have demonstrated survival benefit of combination chemotherapy involving new agents plus cisplatin compared with classic combination chemotherapy in advanced non-small-cell lung cancer (NSCLC). The primary aim of this study was to test whether docetaxel plus cisplatin (DC) improves survival compared with vindesine plus cisplatin (VdsC) in patients with previously untreated stage IV NSCLC. Patients and Methods Eligible, stage IV, chemotherapy-naive patients (n = 311) were randomly assigned to receive docetaxel 60 mg/m2 intravenously on day 1 plus cisplatin 80 mg/m2 intravenously on day 1 of a 3- or 4-week cycle, or vindesine 3 mg/m2 intravenously on days 1, 8, and 15 plus cisplatin 80 mg/m2 intravenously on day 1 of a 4-week cycle. Cross-over administration of docetaxel and vindesine was prohibited for both treatment groups. Results Overall, 302 patients were eligible for evaluation. The DC arm demonstrated significant improvements compared with the VdsC arm in overall response rates (37% v 21%, respectively; P < .01) and median survival times (11.3 v 9.6 months, respectively; P = .014). Two-year survival rates were 24% for the DC arm compared with 12% for the VdsC arm. The physical domain of the Quality of Life for Cancer Patients Treated with Anticancer Drugs measure was significantly better in the DC arm than in the VdsC arm (P = .020). Toxicity was predominantly hematologic and was more severe in the VdsC arm. Conclusion As first-line treatment for stage IV NSCLC, DC resulted in greater clinical benefit in terms of response rate (with marked improvements in overall and 2-year survival rates) and quality of life than did treatment with VdsC.
BRAF Gene Is Somatically Mutated but Does Not Make a Major Contribution to Malignant Melanoma Susceptibility: The Italian Melanoma Intergroup Study
Authors: Casula Milena , Colombino Maria , Satta Maria P. , Cossu Antonio , Ascierto Paolo A. , Bianchi-Scarrà Giovanna , Castiglia Daniele , Budroni Mario , Rozzo Carla , Manca Antonella , Lissia Amelia , Carboni Annangela , Petretto Elisabetta , Satriano Sabrina M.R. , Botti Gerardo , Mantelli Michela , Ghiorzo Paola , Stratton Michael R. , Tanda Francesco , Palmieri Giuseppe 
Published: January 2004

Purpose Oncogenic activation of the BRAF gene has been demonstrated to be involved in the pathogenesis of malignant melanoma (MM). In this study, we investigated the contribution of BRAF to melanoma susceptibility, also making a comparison with frequency of CDKN2A germline mutations in MM patients from different areas in Italy. Patients and Methods Using a combination of denaturing high-performance liquid chromatography analysis and automated sequencing on genomic DNA from peripheral blood or tumor tissue samples, 569 MM patients (211 from northern Italy and 358 from southern Italy) were screened for BRAF mutations. Results Three BRAF germline sequence variants (M116R, V599E, and G608H) were identified in four (0.7%) of 569 MM patients. The most common BRAF mutation, V599E, was detected in one germline DNA sample only; M116R and G608H were newly described mutations. A high frequency (59%) of BRAF mutations was instead observed in tumor samples from patients also undergoing germline DNA analysis; at the somatic level, substitution of valine 599 was found to account for the majority (88%) of BRAF mutations. We then estimated the germline mutation rates in BRAF and CDKN2A among 358 consecutively collected patient samples originating in southern Italy; a low (2.5%) or very low (0.29%) prevalence of CDKN2A and BRAF mutations, respectively, was detected. Conclusion Mutation analysis of either blood DNA from a large collection of MM patients or matched MM tissues from a subset of such patients revealed that BRAF is somatically mutated and does not play a major role in melanoma susceptibility. The present study further suggests that patient origin may account for different mutation rates in candidate genes.
Trends in the Aggressiveness of Cancer Care Near the End of Life
Authors: Earle Craig C. , Neville Bridget A. , Landrum Mary Beth , Ayanian John Z. , Block Susan D. , Weeks Jane C. 
Published: January 2004

Purpose To characterize the aggressiveness of end-of-life cancer treatment for older adults on Medicare, and its relationship to the availability of healthcare resources. Patients and Methods We analyzed Medicare claims of 28,777 patients 65 years and older who died within 1 year of a diagnosis of lung, breast, colorectal, or other gastrointestinal cancer between 1993 and 1996 while living in one of 11 US regions monitored by the Surveillance, Epidemiology, and End Results Program. Results Rates of treatment with chemotherapy increased from 27.9% in 1993 to 29.5% in 1996 (P = .02). Among those who received chemotherapy, 15.7% were still receiving treatment within 2 weeks of death, increasing from 13.8% in 1993 to 18.5% in 1996 (P < .001). From 1993 to 1996, increasing proportions of patients had more than one emergency department visit (7.2% v 9.2%; P < .001), hospitalization (7.8% v 9.1%; P = .008), or were admitted to an intensive care unit (7.1% v 9.4%; P = .009) in the last month of life. Although fewer patients died in acute-care hospitals (32.9% v 29.5%; P < .001) and more used hospice services (28.3% v 38.8%; P < .001), an increasing proportion of patients who received hospice care initiated this service only within the last 3 days of life (14.3% v 17.0%; P = .004). Black patients were more likely than white patients to experience aggressive intervention in nonteaching hospitals but not in teaching hospitals. Greater local availability of hospices was associated with less aggressive treatment near death on multivariate analysis. Conclusion The treatment of cancer patients near death is becoming increasingly aggressive over time.
Different Modes of Gonadotropin-Releasing Hormone (GnRH) Release from Multiple GnRH Systems as Revealed by Radioimmunoassay Using Brain Slices of a Teleost, the Dwarf Gourami (Colisa lalia)
Authors: Ishizaki Mami , Iigo Masayuki , Yamamoto Naoyuki , Oka Yoshitaka 
Published: January 2004

Abstract
It has become a general notion that there are multiple GnRH systems in the vertebrate brains. To measure GnRH release activities from different GnRH systems, we conducted a static incubation of brain-pituitary slices under various conditions, and GnRH released into the incubation medium was measured by RIA. The slices were divided into two parts, one containing GnRH neurons in the preoptic area and axon terminals in the pituitary (POA-GnRH slices), and the other containing the cell bodies and fibers of terminal nerve-GnRH neurons and midbrain tegmentum-GnRH neurons (TN-TEG-GnRH slices). We demonstrated that GnRH release was evoked by high [K+]o depolarizing stimuli (in both POA-GnRH and TN-TEG-GnRH slices) via Ca2+ influx through voltage-gated Ca2+ channels. The most prominent result was the presence of conspicuous sexual difference in the amount of GnRH release in the POA-GnRH slices. The GnRH release from TN-TEG-GnRH slices also showed a small sexual difference, which was by far more inconspicuous than that of POA-GnRH slices. Immunohistochemical analysis using an antiserum specific to the seabream GnRH (sbGnRH; suggested to be specific to POA-GnRH neurons) revealed the presence of a much larger number of POA-GnRH neurons in males than in females. This clear morphological sexual difference is suggested to underlie that of GnRH release in the POA-GnRH slices.
Insulin-Like Growth Factor-Binding Protein-3 in Porcine Ovarian Granulosa Cells: Gene Cloning, Promoter Mapping, and Follicle-Stimulating Hormone Regulation
Authors: Ongeri E. Moige , Zhu Qin , Verderame Michael F. , Hammond James M. 
Published: January 2004

AbstractThe role and regulation of IGF-binding protein-3 (IGFBP-3) in the ovary is not fully understood. We cloned and determined the sequence of 12,257 bp of the pig IGFBP-3 gene that includes 4,296 bp of the flanking promoter sequence. The porcine IGFBP-3 promoter sequence shares two highly conserved regions with the human and bovine IGFBP-3 promoters and a mouse DNA clone. The first is a 38 bp region between −1095 and −1058, whereas the second is a 73-bp region between −63 and +10 of the pig sequence. Projected translation of the open reading frame of our sequence gave a peptide sequence identical to that determined by peptide sequencing, but with 27 additional amino acids upstream of this sequence and is highly similar to the human, bovine, rat, and mouse IGFBP-3 peptides. Using RT-PCR we demonstrated that FSH regulates IGFBP-3 mRNA expression in a biphasic manner, with an early induction (maximal at 3 h) and an inhibition at 24 h after FSH treatment. The inhibition at 24 h was not due to changes in IGFBP-3 mRNA stability. A similar pattern of FSH modulation of the IGFBP-3 gene transcription was demonstrated by the reporter activity of granulosa cells transiently transfected with IGFBP-3 promoter constructs. The site for FSH stimulation of the IGFBP-3 gene was localized to the sequence between −61 and −48 relative to the transcription start site. Regulation of IGFBP-3 transcription by FSH suggests a role for IGFBP-3 in follicular development that may be independent of IGF-I.
In-vitro and in-vivo studies of cefpirom using bile salts as absorption enhancers
Authors: Mrestani Yahya , Bretschneider Beate , Härtl Albert , Neubert Reinhard H H 
Published: January 2004

Abstract
Cephalosporins have to be administered by injection because of the poor intestinal absorption of the orally delivered drugs. Because of the obvious drawbacks of drug delivery by injection, the development of alternatives with enhanced oral bioavailability is receiving much attention in pharmaceutical research. Cefpirom (Cp) is a new semi-synthetic amino-2-thiazolyl-methoxyimino cephalosporin that has been substituted in position 3 with a cyclopenteno-pyridinium group in order to create a zwitterionic compound. It exhibits highly hydrophilic properties, as shown from its extremely low partition coefficient, and therefore its lipophilicity was increased using bile salts. The effect of this on the partition coefficients determined in the n-octanol/buffer system was confirmed using an in-vitro transport model with artificial and biological membranes. The pharmacokinetic properties of Cp were investigated in rabbits after intraduodenal administration with and without bile salts. Furthermore, the physiological compatibility of the bile salts was investigated using active D-glucose transport.
Floating microspheres bearing acetohydroxamic acid for the treatment of Helicobacter pylori
Authors: Umamaheshwari R B , Jain Subheet , Bhadra Dipankar , Jain N K 
Published: January 2004

Abstract
This investigation is part of our ongoing effort to develop effective drug delivery systems for the treatment of Helicobacter pylori infection using polycarbonate (PC) floating microspheres as drug carriers. In an effort to augment the anti-H. pylori effect of acetohydroxamic acid (AHA), floating PC microspheres, which have the ability to reside in the gastrointestinal (GI) tract for an extended period, were prepared by emulsion (O/W) solvent evaporation technique. The effect of PC concentration on the morphology, particle size, entrapment efficiency and drug release rate was studied. In-vitro studies confirmed the excellent floating properties of PC microspheres. In-vitro and in-vivo growth inhibition studies were performed on developed system(s) taking isolated cultures of H. pylori and H. pylori-infected Mongolian gerbils, respectively. The drug and PC microspheres both showed anti-H. pylori activity in vivo, but the required dose of AHA was effectively reduced by a factor of 10 in the case of PC microspheres. In conclusion, the floating microspheres more effectively cleared H. pylori from the GI tract than the drug because of the prolonged gastric residence time resulting from the excellent buoyancy of the PC.
Use of a cholesterol-rich microemulsion that binds to low-density lipoprotein receptors as vehicle for etoposide
Authors: Valduga Claudete J , Fernandes Denise C , Prete Ana C Lo , Azevedo Carolina H M , Rodrigues Debora G , Maranhão Raul C 
Published: January 2004

Abstract
A cholesterol-rich microemulsion (LDE) that binds to low-density lipoprotein (LDL) receptors is selectively taken up by malignant cells that overexpress those receptors and may be used as vehicle for antineoplastic agents. This study aimed to develop the association of etoposide with LDE. It was firstly observed that etoposide poorly associates with the microemulsion, therefore the experiments were performed with a lipophilic fatty acid derivative of the drug. The association of etoposide oleate with LDE was almost 100% and was tested for physical and chemical stability, as well as for cellular uptake, toxicity in mice and cytotoxic activity against a neoplastic cell line (NCI-H292). Uptake and cytotoxic activity of LDE-etoposide oleate by NCI-H292 cells was mediated by LDL receptors. The anti-proliferative activity of LDE-etoposide oleate against the neoplastic cells was smaller than that of etoposide oleate (IC50 (drug concentration required to inhibit 50% of the cell growth) = 0.48 and 0.19 mm, respectively). This difference, however, can be ascribed to the activity of the commercially used vehicle and not the drug itself because when this vehicle was added to the cultures with LDE-etoposide oleate, the IC50 decreased. On the other hand, the tolerability of LDE-etoposide oleate to mice was remarkable, such that its lethal dose (LD50) was about five-fold that of the commercial formulation (LD50=315 and 58 mg kg−1, respectively). In conclusion, LDE-etoposide oleate association is stable and the cytostatic activity of the drug is preserved while its toxicity to animals is small. By diminishing the side effects and directing etoposide to neoplastic tissues, LDE may be regarded as an advance in chemotherapy with this drug.
Pharmacokinetics of thalidomide in patients with impaired renal function and while on and off dialysis
Authors: Eriksson T , Höglund P , Turesson I , Waage A , Don B R , Vu J , Scheffler M , Kaysen G A 
Published: January 2004

Abstract
There is a renewed interest in thalidomide for use in malignancies and systemic inflammatory diseases. Reduced renal function is not uncommon among patients with these disease states but the pharmacokinetics has not been fully investigated. The aim of this study was to investigate the pharmacokinetics of thalidomide in haemodialysis patients while on and off dialysis and in myeloma patients with varying degrees of renal function.
Two studies were performed. To establish the pharmacokinetics of thalidomide in patients with mild to moderate renal failure, blood samples were taken over 12 weeks from 40 patients with multiple myeloma. A second study was performed in six patients with end-stage renal disease both on a non-dialysis day and before and during a haemodialysis session. Thalidomide concentration was determined by HPLC. A one-compartment open model with first-order absorption and elimination was used to fit total thalidomide concentration to population pharmacokinetics and statistical models using the NONMEM program. Clearance and volumes were slightly below 10 L h−1 and 1 L kg−1, respectively, in both patient groups. The inter- and intra-patient variability was low. Clearance was doubled during dialysis. There was no correlation between thalidomide clearance and renal function. In conclusion, the pharmacokinetics of thalidomide in patients with renal failure are very similar to values reported by others for patients with normal renal function. Although clearance during dialysis is doubled, thalidomide dose need not be changed for patients with decreased kidney function. There is also no need for a supplementary dose due to haemodialysis.
Free radical scavenging and antioxidative activity of melatonin derivatives
Authors: Tsia Pen-Lin , Hu Ming-Kuan 
Published: January 2004

Abstract
This article describes the synthesis and antioxidative properties of melatonin derivatives. Tryptamines and cysteinyl or mercaptopropionyl derivatives were deliberately condensed with coupling reagents to give melatonin derivatives 4a–d and 5a, b. The preliminary evaluation indicated that compound 4c showed improved scavenging activity compared with vitamin C (IC50 43 μm vs 65 μm, where IC50 is the concentration of the test compound that induced a change of 50% in absorbance during the 30 min observation) on diphenyl-p-picrylhydrazyl (DPPH) tests. Derivative 5b, which possesses the thiolactyl moiety, showed moderate potency compared with melatonin (IC50 235 μm vs 690 μm) in the H2O2 scavenging test. Intriguingly, 4c displayed 2-fold more potency than melatonin (IC50 51 μm vs 125 μm) in scavenging NO in the macrophage model. These results suggested that the cysteinyl-conjugated derivative 4c may be a suitable lead to further optimize potent antioxidants for certain oxidative stress conditions.