bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnosis and treatment of carotid body paraganglioma: 21 years of experience at a clinical center of Serbia
Authors: Davidovic Lazar B , Djukic Vojko B , Vasic Dragan M , Sindjelic Radomir P , Duvnjak Stevo N 
Published: February 2005

Abstract
Background
The carotid body paraganglioma (chemodectoma) is a relatively rare neoplasm of obscure origin. These are usually benign and commonly present as asymptomatic cervical mass.

Patients and methods
Records of 12 patients (9 female and 3 male) with carotid body tumors treated between 1982 and 2003, treated at our center were retrospectively reviewed. Data on classification, clinical presentation, and surgical treatment were extracted from the case records. Surgical complications and treatment outcome were noted and survival was calculated by actuarial method. The literature on carotid body paraganglioma was reviewed.

Results
The average age of the patients was 52 years (range 30–78 years). Eight of these cases presented as a large asymptomatic non-tender neck mass, and two each presented with dysphagia, and hoarseness of voice. As per Shamblin classification seven of tumors were type II and 5 were types III. In 7 cases subadventitial tumor excision was performed, while in 5 associated resection of both external and internal carotid arteries was carried out. The artery was repaired by end-to-end anastomosis in one case, with Dacron graft in one case, and with saphenous vein graft in 3 cases. There was no operative mortality. After a mean follow-up of 6.2 years (range 6 months to 20 years), there were no signs of tumor recurrence in any of the cases.

Conclusions
Surgical excision is the treatment of choice for carotid body paragangliomas although radiation therapy is an option for patients who are not ideal candidates for surgery. For the tumors that are in intimate contact with carotid arteries, the treatment by vascular surgeon is recommended.
Propagated repolarization of simulated action potentials in cardiac muscle and smooth muscle
Authors: Sperelakis Nicholas , Ramasamy Lakshminarayanan , Kalloor Bijoy 
Published: February 2005

Abstract
Background
Propagation of repolarization is a phenomenon that occurs in cardiac muscle. We wanted to test whether this phenomenon would also occur in our model of simulated action potentials (APs) of cardiac muscle (CM) and smooth muscle (SM) generated with the PSpice program.

Methods
A linear chain of 5 cells was used, with intracellular stimulation of cell #1 for the antegrade propagation and of cell #5 for the retrograde propagation. The hyperpolarizing stimulus parameters applied for termination of the AP in cell #5 were varied over a wide range in order to generate strength / duration (S/D) curves. Because it was not possible to insert a second "black box" (voltage-controlled current source) into the basic units representing segments of excitable membrane that would allow the cells to respond to small hyperpolarizing voltages, gap-junction (g.j.) channels had to be inserted between the cells, represented by inserting a resistor (Rgj) across the four cell junctions.

Results
Application of sufficient hyperpolarizing current to cell #5 to bring its membrane potential (Vm) to within the range of the sigmoidal curve of the Na+ conductance (CM) or Ca++ conductance (SM) terminated the AP in cell #5 in an all-or-none fashion. If there were no g.j. channels (Rgj = ∞), then only cell #5 repolarized to its stable resting potential (RP; -80 mV for CM and -55 mV for SM). The positive junctional cleft potential (VJC) produced only a small hyperpolarization of cell #4. However, if many g.j. channels were inserted, more hyperpolarizing current was required (for a constant duration) to repolarize cell #5, but repolarization then propagated into cells 4, 3, 2, and 1. When duration of the pulses was varied, a typical S/D curve, characteristic of excitable membranes, was produced. The chronaxie measured from the S/D curve was about 1.0 ms, similar to that obtained for muscle membranes.

Conclusions
These experiments demonstrate that normal antegrade propagation of excitation can occur in the complete absence of g.j. channels, and therefore no low-resistance pathways between cells, by the electric field (negative VJC) developed in the narrow junctional clefts. Because it was not possible to insert a second black-box into the basic units that would allow the cells to respond to small hyperpolarizing voltages, only cell #5 (the cell injected with hyperpolarizing pulses) repolarized in an all-or-none manner. But addition of many g.j. channels allowed repolarization to propagate in a retrograde direction over all 5 cells.
Simian immunodeficiency virus (SIV) envelope quasispecies transmission and evolution in infant rhesus macaques after oral challenge with uncloned SIVmac251: increased diversity is associated with neutralizing antibodies and improved survival in previously immunized animals
Authors: Greenier Jennifer L , Van Rompay Koen KA , Montefiori David , Earl Patricia , Moss Bernard , Marthas Marta L 
Published: February 2005

Abstract
Background
Oral infection of infant macaques with simian immunodeficiency virus (SIV) is a useful animal model to test interventions to reduce postnatal HIV transmission via breast-feeding. We previously demonstrated that immunization of infant rhesus macaques with either modified vaccinia virus Ankara (MVA) expressing SIV Gag, Pol and Env, or live-attenuated SIVmac1A11 resulted in lower viremia and longer survival compared to unimmunized controls after oral challenge with virulent SIVmac251 (Van Rompay et al., J. Virology 77:179–190, 2003). Here we evaluate the impact of these vaccines on oral transmission and evolution of SIV envelope variants.

Results
Limiting dilution analysis of SIV RNA followed by heteroduplex mobility assays of the V1–V2 envelope (env) region revealed two major env variants in the uncloned SIVmac251 inoculum. Plasma sampled from all infants 1 week after challenge contained heterogeneous SIV env populations including one or both of the most common env variants in the virus inoculum; no consistent differences in patterns of env variants were found between vaccinated and unvaccinated infants. However, SIV env variant populations diverged in most vaccinated monkeys 3 to 5 months after challenge, in association with the development of neutralizing antibodies.

Conclusions
These patterns of viral envelope diversity, immune responses and disease course in SIV-infected infant macaques are similar to observations in HIV-infected children, and underscore the relevance of this pediatric animal model. The results also support the concept that neonatal immunization with HIV vaccines might modulate disease progression in infants infected with HIV by breast-feeding.
Psychiatric morbidity of overseas patients in inner London: A hospital based study
Authors: Carranza Fredy J , Parshall Alice M 
Published: February 2005

Abstract
Background
Evaluation of the referral, admission, treatment, and outcome of overseas patients admitted to a psychiatric hospital in central London. Ethical, legal and economic implications, and the involvement of consulates in the admission process, are discussed.

Method
Assessment and review of overseas patients admitted between 1 January 1999 and 31 December 1999. Non-parametric statistical tests were used, and relevant outcomes described.

Results
19% of admissions were overseas patients. Mean age was 38 years. 90% were unattached; 84% were white, 71% from European countries. 45% spoke fluent English. Differences in socio-economic status between home country and England were found. 74% were unwell on arrival; 65% travelled to England as tourists.
65% of admissions came via the police. 32% had been ill for more than one year before admission; 68% had psychiatric history. 77% were admitted and 48% discharged under section of the Mental Health Act. 74% had psychotic disorders, all of them with positive symptoms. 55% showed little to moderate improvement in mental state; 10% were on Enhanced Care Programme Approach. Relatives of 48% of patients were contacted.
The Hospital repatriated 52% of patients; the Mental Health Team followed up 13% of those discharged. The average length of admission was 43.4 days (range 1–365). Total cost of admissions was GBP350, 600 ($577, 490); average individual cost was GBP11, 116 (range GBP200-81, 000).

Conclusions
Mentally ill overseas individuals are a vulnerable group that need recognition by health organisations to adapt current practice to better serve their needs. The involvement of consulates needs further evaluation.
A DNA microarray survey of gene expression in normal human tissues
Authors: Shyamsundar Radha , Kim Young H , Higgins John P , Montgomery Kelli , Jorden Michelle , Sethuraman Anand , van de Rijn Matt , Botstein David , Brown Patrick O , Pollack Jonathan R 
Published: February 2005

Abstract
Background
Numerous studies have used DNA microarrays to survey gene expression in cancer and other disease states. Comparatively little is known about the genes expressed across the gamut of normal human tissues. Systematic studies of global gene-expression patterns, by linking variation in the expression of specific genes to phenotypic variation in the cells or tissues in which they are expressed, provide clues to the molecular organization of diverse cells and to the potential roles of the genes.

Results
Here we describe a systematic survey of gene expression in 115 human tissue samples representing 35 different tissue types, using cDNA microarrays representing approximately 26,000 different human genes. Unsupervised hierarchical cluster analysis of the gene-expression patterns in these tissues identified clusters of genes with related biological functions and grouped the tissue specimens in a pattern that reflected their anatomic locations, cellular compositions or physiologic functions. In unsupervised and supervised analyses, tissue-specific patterns of gene expression were readily discernable. By comparative hybridization to normal genomic DNA, we were also able to estimate transcript abundances for expressed genes.

Conclusions
Our dataset provides a baseline for comparison to diseased tissues, and will aid in the identification of tissue-specific functions. In addition, our analysis identifies potential molecular markers for detection of injury to specific organs and tissues, and provides a foundation for selection of potential targets for selective anticancer therapy.
Phase I Pharmacokinetic and Pharmacodynamic Study of Weekly 1-Hour and 24-Hour Infusion BMS-214662, a Farnesyltransferase Inhibitor, in Patients With Advanced Solid Tumors
Authors: Tabernero Josep , Rojo Fredy , Marimón Irene , Voi Maurizio , Albanell Joan , Guix Marta , Vázquez Federico , Carulla Joan , Cooper Michael , Andreu Jordi , Van Vreckem Anne , Bellmunt Joaquim , Manne Veeraswamy , Manning James A. , Garrido Carmen , Felip Enriqueta , del Campo Josep Maria , García Mónica , Valverde Sonia , Baselga José 
Published: February 2005

Purpose BMS-214662 is a potent, nonpeptide, small molecule inhibitor of human farnesyltransferase (FT). We have conducted a phase I pharmacokinetic (PK) and pharmacodynamic study of BMS-214662 administered intravenously weekly with 1- and 24-hour infusions. The objectives were to determine the dose-limiting toxicities and the recommended dose (RD), to describe PKs, and to evaluate the relationships between BMS-214662 exposure, FT inhibition, downstream signaling, and induction of apoptosis in tumor samples. Patients and Methods Patients with advanced solid tumors and adequate organ function were eligible. The dose was escalated according to a modified Fibonacci schedule. Results BMS-214662 was escalated from 56 to 278 mg/m2 in 37 patients in the 1-hour schedule, and from 84 to 492 mg/m2 in 31 patients in the 24-hour schedule. Dose-limiting toxicities included gastrointestinal and renal events. The RDs were 209 mg/m2 and 275 mg/m2 in the 1- and 24-hour schedules, respectively. Five patients (three with breast, one with gastric, and one with renal cell cancer) had clinical benefit from treatment. BMS-214662 exhibited linear PKs with area under the concentration-time curves at the RDs of 27 and 32 μM × h in the 1- and 24-hour schedules, respectively. The pattern of FT inhibition in peripheral-blood mononuclear cells at the RDs was different in the two schedules: high (> 80%) but short-lived (≤ 6 hours) in the 1-hour infusion and moderate (> 40%) but long-lived (24 hours) in the 24-hour infusion. BMS-214662 induced apoptosis in tumors but did not inhibit MAPK signaling. Conclusion BMS-214662 can be safely delivered in both the 1-hour and 24-hour infusions at biologically active doses, with the preclinical, PK, and pharmacodynamic profiles favoring the 24-hour schedule.
Neoadjuvant Trastuzumab Induces Apoptosis in Primary Breast Cancers
Authors: Mohsin Syed K. , Weiss Heidi L. , Gutierrez M. Carolina , Chamness Gary C. , Schiff Rachel , DiGiovanna Michael P. , Wang Chun-Xia , Hilsenbeck Susan G. , Osborne C. Kent , Allred D. Craig , Elledge Richard , Chang Jenny C. 
Published: February 2005

Purpose Greater understanding of the cellular response in trastuzumab-treated patients will provide insight into the clinical management of patients. Patients and Methods We performed a neoadjuvant trial in 35 patients with locally advanced HER-2/neu overexpressing breast cancers who received weekly trastuzumab given as a single agent for the first 3 weeks, followed by a combination of trastuzumab and docetaxel for 12 weeks before surgery. Sequential core biopsies were taken at baseline and within weeks 1 and 3 after the first dose of trastuzumab. Clinical response to trastuzumab was assessed by tumor measurements on day 22 before chemotherapy. Core biopsies were assessed by immunohistochemistry for cell cycle and proliferation (Ki67, p27, phosphorylated [p] -MAPK), apoptosis and survival (apoptotic index, p-Akt), epidermal growth factor receptor, and total and p-HER-2. Results There was early tumor regression with a median decrease of −20.0% (range. 0% to 60.4%) after only 3 weeks of trastuzumab, and eight patients (23%) had a partial response. Consistent with the clinical regressions, apoptosis was significantly induced (median increase from 3.5% to 4.7%; P = .006) within week 1, a 35% increase above baseline. No significant change in epidermal growth factor receptor score was observed in week 1, without changes in total or p-HER-2 expression. Tumors with high baseline Ki67 were less likely to respond (P = .02). Conclusion In primary breast cancers, trastuzumab substantially induces apoptosis, providing a molecular explanation for both its therapeutic efficacy and its successful combination with cytotoxic chemotherapy.
Randomized Phase II Study of Two Gemcitabine Schedules for Patients With Impaired Performance Status (Karnofsky performance status ≤ 70) and Advanced Non–Small-Cell Lung Cancer
Authors: Baka S. , Ashcroft L. , Anderson H. , Lind M. , Burt P. , Stout R. , Dowd I. , Smith D. , Lorigan P. , Thatcher N. 
Published: February 2005

PurposeThis randomized phase II study compared two treatment schedules of gemcitabine in patients with non–small-cell lung cancer (NSCLC) and impaired Karnofsky performance status (KP). Primary objectives were to record changes from baseline KP and to assess symptom palliation. Secondary objectives were overall survival, tumor response, and toxicity.Patients and MethodsPatients with stage IIIb and IV NSCLC and KP ≤ 70 were randomly assigned to receive gemcitabine 1,000 mg/m2on days 1, 8, and 15 of each 28-day cycle (3w4) or gemcitabine 1,500 mg/m2on days 1 and 8 of each 21-day cycle (2w3), both for up to six cycles. KP, toxicity, and SS14 lung cancer specific questions were recorded before each cycle of treatment. Response was evaluated 4 weeks after the last cycle.ResultsOne hundred seventy-four patients were enrolled. There was significant early attrition due to disease progression; only 61.5% of patients were alive at 2 months. There was a significant improvement in KP from baseline to pre–cycle 3 in both arms, with a trend in favor of the 3w4 regimen for duration and faster onset of improvement. Eight of the 17 quality-of-life (QOL) variables assessed showed an improvement of more than 10% between baseline and the start of the third cycle of treatment. Response rate, survival, and duration were similar in both arms.ConclusionThere was no significant difference between the two schedules examined in terms of improvement in KP or QOL, but there seemed to be a trend in favor of the 3w4 schedule.
Predictive and Prognostic Impact of Epidermal Growth Factor Receptor Mutation in Non–Small-Cell Lung Cancer Patients Treated With Gefitinib
Authors: Han Sae-Won , Kim Tae-You , Hwang Pil Gyu , Jeong Soohyun , Kim Jeongmi , Choi In Sil , Oh Do-Youn , Kim Jee Hyun , Kim Dong-Wan , Chung Doo Hyun , Im Seock-Ah , Kim Young Tae , Lee Jong Seok , Heo Dae Seog , Bang Yung-Jue , Kim Noe Kyeong 
Published: February 2005

Purpose This study was undertaken to investigate the effects of epidermal growth factor receptor (EGFR) mutation and its downstream signaling on response and survival in non–small-cell lung cancer (NSCLC) patients treated with gefitinib. Patients and Methods For 90 consecutive NSCLC patients who had received gefitinib, EGFR mutation was analyzed by DNA sequencing of exons 18, 19, 21, and 23 in the EGFR tyrosine kinase domain. Expressions of phosphorylated (p) -Akt and p-Erk were determined via immunohistochemistry. Response rate, time to progression (TTP), and overall survival were compared between each group according to EGFR mutation, as well as p-Akt and p-Erk expression. Results Seventeen patients (18.9%; 95% CI, 10.8 to 27.0) harbored EGFR mutations. These mutations include deletions in exon 19 in seven patients, L858R in six patients, G719A in three patients, and a novel A859T in one patient. Response rate in patients with EGFR mutation was 64.7% (11 of 17 patients; 95% CI, 42.0 to 87.4), in contrast to 13.7% (10 of 73 patients; 95% CI, 5.8 to 21.6) in patients without mutation (P < .001). Moreover, these 17 patients with EGFR mutation had significantly prolonged TTP (21.7 v 1.8 months; P < .001) and overall survival (30.5 v 6.6 months; P < .001) compared with the remaining 73 patients without mutation. Although no significant correlation was detected between EGFR mutation and expressions of p-Akt or p-Erk, p-Akt overexpression was associated with prolonged TTP in patients with EGFR mutation. Conclusion Our data further support the importance of EGFR mutation with regard to gefitinib sensitivity. In addition to its predictive role, EGFR mutation confers significant survival benefits on NSCLC patients treated with gefitinib.
Safety and Efficacy of Two Different Doses of Capecitabine in the Treatment of Advanced Breast Cancer in Older Women
Authors: Bajetta Emilio , Procopio Giuseppe , Celio Luigi , Gattinoni Luca , Della Torre Silvia , Mariani Luigi , Catena Laura , Ricotta Riccardo , Longarini Raffaella , Zilembo Nicoletta , Buzzoni Roberto 
Published: February 2005

Purpose To evaluate the safety and efficacy of capecitabine in older women with advanced breast cancer. Patients and Methods Seventy-three eligible patients (median age, 73 years; range, 65 to 89 years) were enrolled. The first 30 patients received oral capecitabine 1,250 mg/m2 twice daily on days 1 to 14 every 21 days. Due to the occurrence of two toxic deaths, capecitabine 1,000 mg/m2 twice daily was given to the subsequent 43 patients. Results All patients were assessable for safety and efficacy. A total of 351 treatment cycles were administered (median, six per patient; range, one to eight cycles). Dose reductions due to toxicities were required in 30% of patients in the standard-dose group, but capecitabine was given without a dose reduction to 95% of patients in the low-dose group. Capecitabine demonstrated a favorable safety profile. The overall incidence of grade 3/4 toxicities was low: the most common events reported in ≤ 10% of the patients were fatigue, diarrhea, dyspnea, and nausea. In the standard-dose group, the response rate was 36.7% (95% CI, 19.9% to 56.1%). An additional seven patients had disease stabilization at ≥ 24 weeks. In the low-dose group, the response rate was 34.9% (95% CI, 21% to 50.9%). An additional 15 patients had prolonged stabilization. The median time to disease progression was 4 months in either group. Conclusion This study shows that capecitabine is safe and effective in the elderly breast cancer patient. Based on the overall results, the capecitabine dose of 1,000 mg/m2 twice daily merits consideration as “standard” for older patients who do not have severely impaired renal function.
Vascular and Neoplastic Risk in a Large Cohort of Patients With Polycythemia Vera
Authors: Marchioli Roberto , Finazzi Guido , Landolfi Raffaele , Kutti Jack , Gisslinger Heinz , Patrono Carlo , Marilus Raphael , Villegas Ana , Tognoni Gianni , Barbui Tiziano 
Published: February 2005

Purpose The clinical course of polycythemia vera is often complicated by thrombosis as well as by the possible transition to myeloid metaplasia with myelofibrosis or acute myeloid leukemia. The aim of this study was to assess the rate of these complications in subjects receiving currently recommended treatments. Patients and Methods Overall, 1,638 patients from 12 countries were enrolled onto a large, prospective multicenter project aimed at describing the clinical history of polycythemia vera for the following outcomes: survival, the cumulative rate of cardiovascular death and thrombosis, the cumulative rate of leukemia, myelodysplasia, and myelofibrosis. The mean duration of the disease at entry and the duration of the follow-up were 4.9 and 2.7 years, respectively. Results The overall mortality rate of 3.7 deaths per 100 persons per year resulted from a moderate risk of cardiovascular death and a high risk of death from noncardiovascular causes (mainly hematologic transformations). Age older than 65 years and a positive history of thrombosis were the most important predictors of cardiovascular events. Antiplatelet therapy, but not cytoreductive treatment, was significantly associated with a lower risk of cardiovascular events. We found a consistent association between age and risk of leukemia, and between duration of the disease with risk of myelofibrosis. Conclusion The European Collaboration on Low-Dose Aspirin in Polycythemia Vera study documents that large international collaborative studies are feasible in this field, in which few epidemiologic data are available. The persistently high mortality rate from hematologic malignancies characterizes the unmet therapeutic need of polycythemic patients and suggests a priority for future studies in this disease.