bluuebunny/crossref_metadata_2025_split huggingface dataset:
Upper limb neuropathy in computer operators? A clinical case study of 21 patients
Authors: Jepsen Jørgen Riis 
Published: August 2004

Abstract
Background
The character of upper limb disorder in computer operators remains obscure and their treatment and prevention have had limited success. Symptoms tend to be mostly perceived as relating to pathology in muscles, tendons or insertions. However, the conception of a neuropathic disorder would be supported by objective findings reflecting the common complaints of pain, subjective weakness, and numbness/tingling. By examining characteristics in terms of symptoms, signs, and course, this study aimed at forming a hypothesis concerning the nature and consequences of the disorder.

Methods
I have studied a consecutive series of 21 heavily exposed and severely handicapped computer-aided designers. Their history was recorded and questionnaire information was collected, encompassing their status 1/2 – 1 1/2 years after the initial clinical contact. The physical examination included an assessment of the following items: Isometric strength in ten upper limb muscles; sensibility in five homonymously innervated territories; and the presence of abnormal tenderness along nerve trunks at 14 locations.

Results
Rather uniform physical findings in all patients suggested a brachial plexus neuropathy combined with median and posterior interosseous neuropathy at elbow level. In spite of reduced symptoms at follow-up, the prognosis was serious in terms of work-status and persisting pain.

Conclusions
This small-scale study of a clinical case series suggests the association of symptoms to focal neuropathy with specific locations. The inclusion of a detailed neurological examination would appear to be advantageous with upper limb symptoms in computer operators.
Analysis of HIV-1 Vpr determinants responsible for cell growth arrest in Saccharomyces cerevisiae
Authors: Yao Xiao-Jian , Rougeau Nicole , Duisit Ghislaine , Lemay Julie , Cohen Éric A 
Published: August 2004

Abstract
Background
The HIV-1 genome encodes a well-conserved accessory gene product, Vpr, that serves multiple functions in the retroviral life cycle, including the enhancement of viral replication in nondividing macrophages, the induction of G2 cell-cycle arrest, and the modulation of HIV-1-induced apoptosis. We previously reported the genetic selection of a panel of di-tryptophan (W)-containing peptides capable of interacting with HIV-1 Vpr and inhibiting its cytostatic activity in Saccharomyces cerevisiae (Yao, X.-J., J. Lemay, N. Rougeau, M. Clément, S. Kurtz, P. Belhumeur, and E. A. Cohen, J. Biol. Chem. v. 277, p. 48816–48826, 2002). In this study, we performed a mutagenic analysis of Vpr to identify sequence and/or structural determinants implicated in the interaction with di-W-containing peptides and assessed the effect of mutations on Vpr-induced cytostatic activity in S. cerevisiae.

Results
Our data clearly shows that integrity of N-terminal α-helix I (17–33) and α-helix III (53–83) is crucial for Vpr interaction with di-W-containing peptides as well as for the protein-induced cytostatic effect in budding yeast. Interestingly, several Vpr mutants, mainly in the N- and C-terminal domains, which were previously reported to be defective for cell-cycle arrest or apoptosis in human cells, still displayed a cytostatic activity in S. cerevisiae and remained sensitive to the inhibitory effect of di-W-containing peptides.

Conclusions
Vpr-induced growth arrest in budding yeast can be effectively inhibited by GST-fused di-W peptide through a specific interaction of di-W peptide with Vpr functional domain, which includes α-helix I (17–33) and α-helix III (53–83). Furthermore, the mechanism(s) underlying Vpr-induced cytostatic effect in budding yeast are likely to be distinct from those implicated in cell-cycle alteration and apoptosis in human cells.
Early Detection and Prognosis of Ovarian Cancer Using Serum YKL-40
Authors: Dupont Jakob , Tanwar Meena K. , Thaler Howard T. , Fleisher Martin , Kauff Noah , Hensley Martee L. , Sabbatini Paul , Anderson Sibyl , Aghajanian Carol , Holland Eric C. , Spriggs David R. 
Published: August 2004

Purpose YKL-40 is a secreted glycoprotein (chitinase family). We compared YKL-40 with two ovarian cancer serum markers, CA125 and CA15-3, for the detection of early-stage ovarian cancer. Materials and Methods Serum YKL-40 levels were assayed by enzyme-linked immunosorbent assay for 46 healthy subjects, 61 high-risk individuals, 33 patients with benign gynecologic processes, and 50 preoperative patients subsequently diagnosed with predominantly early-stage ovarian cancer. Serum CA125 and CA15-3 values were obtained. Results Median YKL-40 level was 28 ng/mL (range, 15 to 166 ng/mL) for healthy subjects, 36 ng/mL (range, 9 to 69 ng/mL) for high-risk individuals without prior cancer, 44.5 ng/mL (range, 5 to 133 ng/mL) for high-risk patients with prior breast cancer, and 38 ng/mL (range, 5 to 67 ng/mL) for individuals with benign gynecologic processes (P = NS). Median preoperative YKL-40 level for ovarian cancer patients was 94 ng/mL (range, 17 to 517 ng/mL; P < .0001 compared with normal and high-risk). YKL-40 was elevated (≥ 62 ng/mL) in 36 (72%) of 50 patients compared with 23 (46%) of 50 and 13 (26%) of 50 patients for CA125 and CA15-3 (P < .008). Twenty (65%) of 31 early-stage patients had elevated serum YKL-40 levels compared with 11 (35%) of 31 and four (13%) of 31 patients for CA125 and CA15-3 (P = .039). YKL-40 levels increased with stage (P < .005), regardless of grade, histology, or patient age. Patients with early-stage tumors with YKL-40 values more than 80 ng/mL had a worse prognosis (71% recurrence v no recurrence [P = .034]). Conclusion YKL-40 may represent a novel marker for the detection of early-stage ovarian cancer. YKL-40 levels in early-stage patients may also predict disease recurrence and survival. The utility of YKL-40 in detection of early-stage ovarian cancer deserves further investigation.
Cytoreductive Surgery Combined With Perioperative Intraperitoneal Chemotherapy for the Management of Peritoneal Carcinomatosis From Colorectal Cancer: A Multi-Institutional Study
Authors: Glehen O. , Kwiatkowski F. , Sugarbaker P.H. , Elias D. , Levine E.A. , De Simone M. , Barone R. , Yonemura Y. , Cavaliere F. , Quenet F. , Gutman M. , Tentes A.A.K. , Lorimier G. , Bernard J.L. , Bereder J.M. , Porcheron J. , Gomez-Portilla A. , Shen P. , Deraco M. , Rat P. 
Published: August 2004

Purpose The three principal studies dedicated to the natural history of peritoneal carcinomatosis (PC) from colorectal cancer consistently showed median survival ranging between 6 and 8 months. New approaches combining cytoreductive surgery and perioperative intraperitoneal chemotherapy suggest improved survival. Patients and Methods A retrospective multicenter study was performed to evaluate the international experience with this combined treatment and to identify the principal prognostic indicators. All patients had cytoreductive surgery and perioperative intraperitoneal chemotherapy (intraperitoneal chemohyperthermia and/or immediate postoperative intraperitoneal chemotherapy). PC from appendiceal origin was excluded. Results The study included 506 patients from 28 institutions operated between May 1987 and December 2002. Their median age was 51 years. The median follow-up was 53 months. The morbidity and mortality rates were 22.9% and 4%, respectively. The overall median survival was 19.2 months. Patients in whom cytoreductive surgery was complete had a median survival of 32.4 months, compared with 8.4 months for patients in whom complete cytoreductive surgery was not possible (P < .001). Positive independent prognostic indicators by multivariate analysis were complete cytoreduction, treatment by a second procedure, limited extent of PC, age less than 65 years, and use of adjuvant chemotherapy. The use of neoadjuvant chemotherapy, lymph node involvement, presence of liver metastasis, and poor histologic differentiation were negative independent prognostic indicators. Conclusion The therapeutic approach combining cytoreductive surgery with perioperative intraperitoneal chemotherapy achieved long-term survival in a selected group of patients with PC from colorectal origin with acceptable morbidity and mortality. The complete cytoreductive surgery was the most important prognostic indicator.
Results of a Phase II Upfront Window of Pharmacokinetically Guided Topotecan in High-Risk Medulloblastoma and Supratentorial Primitive Neuroectodermal Tumor
Authors: Stewart Clinton F. , Iacono Lisa C. , Chintagumpala Murali , Kellie Stewart J. , Ashley David , Zamboni W.C. , Kirstein M.N. , Fouladi Maryam , Seele Louis G. , Wallace Dana , Houghton Peter J. , Gajjar Amar 
Published: August 2004

Purpose To assess the antitumor efficacy of pharmacokinetically guided topotecan dosing in previously untreated patients with medulloblastoma and supratentorial primitive neuroectodermal tumors, and to evaluate plasma and CSF disposition of topotecan in these patients. Patients and Methods After maximal surgical resection, 44 children with previously untreated high-risk medulloblastoma were enrolled, of which 36 were assessable for response. The topotecan window consisted of two cycles, administered initially as a 30-minute infusion daily for 5 days, lasting 6 weeks. Pharmacokinetic studies were conducted on day 1 to attain a topotecan lactone area under the plasma concentration-time curve (AUC) of 120 to 160 ng/mL·h. After 10 patients were enrolled, the infusion was modified to 4 hours, with dosage individualization. Results Of 36 assessable patients, four patients (11.1%) had a complete response and six (16.6%) showed a partial response, and disease was stable in 17 patients (47.2%). Toxicity was mostly hematologic, with only one patient experiencing treatment delay. The target plasma AUC was achieved in 24 of 32 studies (75%) in the 30-minute infusion group, and in 58 of 93 studies (62%) in the 4-hour infusion group. The desired CSF topotecan exposure was achieved in seven of eight pharmacokinetic studies when the topotecan plasma AUC was within target range. Conclusion Topotecan is an effective agent against pediatric medulloblastoma in patients who have received no therapy other than surgery. Pharmacokinetically guided dosing achieved the target plasma AUC in the majority of patients. This drug warrants testing as part of standard postradiation chemotherapeutic regimens. Furthermore, these results emphasize the importance of translational research in drug development, which in this case identified an effective drug.
Positron Emission Tomography in Limited-Stage Small-Cell Lung Cancer: A Prospective Study
Authors: Bradley Jeffrey D. , Dehdashti Farrokh , Mintun Mark A. , Govindan Ramaswamy , Trinkaus Kim , Siegel Barry A. 
Published: August 2004

Purpose To determine how often positron emission tomography with [18F]fluoro-2-deoxy-D-glucose (FDG-PET) detects extensive-stage small-cell lung cancer (SCLC) in patients considered to have limited-stage disease based on conventional staging procedures, and to determine the impact of PET on treatment planning for presumed limited-stage SCLC. Patients and Methods We prospectively performed pretreatment FDG-PET on 24 patients determined by conventional staging methods to have limited-stage SCLC (defined as disease that could be encompassed within a reasonable radiotherapy portal, excluding bilateral supraclavicular disease). PET images were evaluated for evidence of extensive-stage disease. Tumor-node-metastasis system staging was also assigned for each patient, with and without PET information. Results FDG-PET demonstrated findings consistent with extensive-stage SCLC in three of 24 patients. FDG-PET correctly upstaged two (8.3%) of 24 patients to extensive-stage disease (95% CI, 1.03% to 27.0%). PET correctly identified tumor in each SCLC mass (primary or nodal) that was suspected on computed tomography (CT) imaging, thus giving a lesion-based sensitivity relative to CT of 100%. PET identified unsuspected regional nodal metastasis in six (25%) of 24 patients, and the radiation therapy plan was significantly altered to include the PET-positive/CT-negative nodes within the high-dose region in each of these patients. Brain PET images in 23 patients disclosed no evidence of brain metastasis. Conclusion FDG-PET has high sensitivity for SCLC and appears to be of value for initial staging and treatment planning of patients with presumed limited-stage disease.
Preoperative F-18 Fluorodeoxyglucose-Positron Emission Tomography Maximal Standardized Uptake Value Predicts Survival After Lung Cancer Resection
Authors: Downey Robert J. , Akhurst Timothy , Gonen Mithat , Vincent Alain , Bains Manjit S. , Larson Steven , Rusch Valerie 
Published: August 2004

Purpose A retrospective review of surgically treated lung cancer patients imaged preoperatively by F-18 fluorodeoxyglucose–positron emission tomography ([18F]FDG-PET) to determine if the primary tumor standardized uptake value (SUV) predicts survival. Patients and Methods Non–small-cell lung cancer or carcinoid pT1–4, N0–2, M0 patients treated by R0 surgical resection alone were imaged with computed tomography scan and PET within 90 days before surgery. Prognostic variables were assessed by log-rank test; survival was assessed by the method of Kaplan and Meier. Results One hundred consecutive patients (48 men, 52 women) were retrospectively reviewed. Median follow-up for surviving patients was 28 months (range, 16 to 81 months). Median maximal SUV (SUVMAX) was 9. The 2-year survival for patients with SUVMAX more than 9 was 68% and for those with SUVMAX less than 9, it was 96% (P < .01, log-rank test). In a multivariate analysis including pathologic tumor size, involved nodes, histology, and SUVMAX, only tumor size (T) more than 3 cm and SUVMAX more than 9 and their interaction were significant predictors of survival (P = .01, 0.02, and < 0.01, respectively). The 3-year survivals for patients with both T less than 3 cm and SUVMAX less than 9 was 97%; for those with T less than 3 cm and SUVMAX more than 9, it was 94%; for those with T more than 3 cm and SUVMAX less than 9, it was 93%; and for those with T more than 3 cm and SUVMAX more than 9, it was 47% (P < .01). Conclusion In surgically managed lung cancer patients, SUV is a predictor of overall survival after resection. The addition of SUVMAX to pathologic tumor size identifies a subgroup of patients at highest risk for death as a result of recurrent disease after resection.
Phase II Study of Cisplatin and Vinorelbine in Squamous Cell Carcinoma of the Cervix: A Gynecologic Oncology Group Study
Authors: Morris Mitchell , Blessing John A. , Monk Bradley J. , McGehee Ramon , Moore David H. 
Published: August 2004

Purpose To evaluate the efficacy and toxicity of intravenous cisplatin and vinorelbine as combination chemotherapy in patients with advanced or recurrent squamous cell carcinoma of the cervix. Patients and Methods Between August 1997 and January 2001, 73 patients with advanced or recurrent squamous cell carcinoma of the cervix were entered onto this study. Eligible patients had received no prior therapeutic chemotherapy, except when administered concurrent with primary radiation therapy. The initial doses administered were cisplatin 75 mg/m2 every 4 weeks and vinorelbine 30 mg/m2 weekly. Subsequent doses were unchanged, reduced, escalated, or omitted according to observed toxicity and protocol guidelines. Patients were evaluated for response and toxicity using standard Gynecologic Oncology Group criteria. Results Of 73 patients, 67 were eligible and assessable. The overall response rate was 30% (five complete and 15 partial responses). The overall median response duration was 5.5+ months. The major toxicity was neutropenia, with 16% grade 3 and 67% grade 4 reported. Gastrointestinal and neurotoxicity were infrequent and mild. Conclusion The combination of cisplatin and vinorelbine has moderate activity in advanced or recurrent squamous cell carcinoma of the cervix. Additional study of this regimen in a phase III setting is justified in this patient population.
Oil-based formulations for oral delivery of insulin
Authors: Li Chun-Lei , Deng Ying-Jie 
Published: August 2004

Abstract
Several oil-based solution formulations of insulin were prepared, in which insulin was solubilized in the form of anhydrous reverse micelles. The preparation process involved micellar dissolution of insulin followed by freeze drying, then reconstitution of lyophilized product with an oil phase. These formulations were stable at room temperature for up to 12 months. No significant changes in the appearance were observed and no degradation products of insulin were detected during the course of the stability study. The efficacy of these formulations was evaluated in-vivo using diabetic Wistar rat as an animal model and then a specific formulation was chosen for further study in non-diabetic New Zealand rabbits. It was found that the efficacy of insulin oil solution was dose dependent and insulin oil solution had the same efficacy as insulin emulsion with the same formulation composition. If ethylene-diaminetetraacetic acid (EDTA) was pre-delivered 40 min before the delivery of insulin oil solution, the hypoglycaemic effect of insulin oil solution was greatly enhanced, with an AUC (% glucose reduced) value increase from 28.5 ± 14.7 to 167.1 ± 72.3. The improvement of oral absorption induced by pre-delivery of EDTA might be attributed to enzyme inhibition, reduced gut mobility and the opening of paracellular routes.
LSox5 regulates RhoB expression in the neural tube and promotes generation of the neural crest
Authors: Perez-Alcala Siro , Nieto M. Angela , Barbas Julio A. 
Published: August 2004

Members of the Sox family of transcription factors are involved in a number of crucial developmental processes, including sex determination, neurogenesis and skeletal development. LSox5 is a member of the group D Sox factors that,in conjunction with Sox6 and Sox9, promotes chondrogenesis by activating the expression of cartilage-specific extracellular matrix molecules. We have cloned the chicken homologue of LSox5 and found that it is initially expressed in the premigratory and migratory neural crest after Slugand FoxD3. Subsequently, the expression of LSox5 is maintained in cephalic crest derivatives, and it appears to be required for the development of the glial lineage, the Schwann cells and satellite glia in cranial ganglia.Misexpression of LSox5 in the cephalic neural tube activated RhoB expression throughout the dorsoventral axis. Furthermore, the prolonged forced expression of LSox5 enlarged the dorsal territory in which the neural crest is generated, extended the `temporal window' of neural crest segregation, and led to an overproduction of neural crest cells in cephalic regions. In addition to HNK-1, the additional neural crest cells expressed putative upstream markers (Slug, FoxD3) indicating that a regulatory feedback mechanism may operate during neural crest generation. Thus, our data show that in addition to the SoxE genes(Sox9 and Sox10) a SoxD gene (Sox5) also participates in neural crest development and that a cooperative interaction may operate during neural crest generation, as seen during the formation of cartilage.
On the Jump of Buckling Capacity of Beams via Piezoelectric Layers
Authors: Wang Q. 
Published: August 2004

The paper presents research on the effect of a follower tensile force on the buckling capacity of beam structures subjected to non-follower compression. The potential of the research is for the application of smart materials on the buckling enhancement of beams, since the follower force is always and properly modelled at the interaction between the smart materials and the substrate. The buckling capacities of beams with different boundary conditions are obtained analytically. The phenomenon of a jump in buckling capacity for beams with one end fixed and the other end restrained by a translational spring is found. This observation indicates that by properly applying a follower force through the use of smart materials, the buckling capacities of a beam can be enhanced dramatically. The voltage, needed for the jump in the buckling capacity, applied to a pair of piezoelectric layers is hence studied and properly made. It is hoped that this work will enable designers to capitalise on the effectiveness of piezoelectric actuators or Shape Memory Alloy (SMA) in enhancing the buckling capacities of beams.
Sensitivity and Specificity of Single-Nucleotide Polymorphism Scanning by High-Resolution Melting Analysis
Authors: Reed Gudrun H , Wittwer Carl T 
Published: August 2004

Abstract
Background: Screening for heterozygous sequence changes in PCR products, also known as “mutation scanning”, is an important tool for genetic research and clinical applications. Conventional methods require a separation step.
Methods: We evaluated the sensitivity and specificity of homogeneous scanning, using a saturating DNA dye and high-resolution melting. Heterozygous single-nucleotide polymorphism (SNP) detection was studied in three different sequence backgrounds of 40%, 50%, and 60% GC content. PCR products of 50–1000 bp were generated in the presence of LCGreen™ I. After fluorescence normalization and temperature overlay, melting curve shape was used to judge the presence or absence of heterozygotes among 1632 cases.
Results: For PCR products of 300 bp or less, all 280 heterozygous and 296 wild-type cases were correctly called without error. In 672 cases between 400 and 1000 bp with the mutation centered, the sensitivity and specificity were 96.1% and 99.4%, respectively. When the sequence background and product size with the greatest error rate were used, the sensitivity of off-center SNPs (384 cases) was 95.6% with a specificity of 99.4%. Most false negatives occurred with SNPs that were compared with an A or T wild type sequence.
Conclusions: High-resolution melting analysis with the dye LCGreen I identifies heterozygous single-base changes in PCR products with a sensitivity and specificity comparable or superior to nonhomogeneous techniques. The error rate of scanning depends on the PCR product size and the type of base change, but not on the position of the SNP. The technique requires only PCR reagents, the dye LCGreen I, and 1–2 min of closed-tube, post-PCR analysis.