bluuebunny/crossref_metadata_2025_split huggingface dataset:
Classical diseases revisited: transient global amnesia
Authors: Owen D , Paranandi B , Sivakumar R , Seevaratnam M 
Published: April 2007

Abstract
Transient global amnesia usually affects patients between the ages of 40 and 80. Patients with this condition are often described – wrongly – as being confused. It presents classically with an abrupt onset of severe anterograde amnesia. It is usually accompanied by repetitive questioning. The patient does not have any focal neurological symptoms. Patients remain alert, attentive, and cognition is not impaired. However, they are disoriented to time and place. Attacks usually last for 1–8 h but should be less than 24 h. It is possible that it may result from different mechanisms such as venous congestion with valsalva-like activities before symptom onset, arterial thromboembolic ischaemia and vasoconstriction due to hyperventilation. Diagnosis may be made safely in the presence of a characteristic collateral history. No specific treatment is indicated for a typical episode.
Vitamin D in childhood and adolescence
Authors: Cashman Kevin D 
Published: April 2007

Abstract
It is well-established that prolonged and severe vitamin D deficiency leads to rickets in children and osteomalacia in adults. More marginal vitamin D deficiency is likely to be a significant contributing factor to osteoporosis risk. However, recent emerging data from studies of adults suggest that low vitamin D status (serum 25-hydroxyvitamin D levels &lt;50 nmol/l) may be contributing to the development of various chronic diseases, including cardiovascular disease, hypertension, diabetes mellitus, some inflammatory and autoimmune diseases, and certain cancers. Adequacy of vitamin D status in children and adolescents has been the focus of a number of recent investigations, and these studies have shown a high prevalence of low vitamin D status during the winter (especially in adolescents), with lower prevalence during the summer. Therefore, consideration of potential corrective strategies to allow children and adolescents to maintain adequate vitamin D status throughout the year, even in the absence of adequate summer sun exposure, is warranted.
Islet cell transplantation
Authors: Srinivasan P , Huang G C , Amiel S A , Heaton N D 
Published: April 2007

Abstract
People with type 1 diabetes have normal exocrine pancreatic function, making islet cell rather than whole organ transplantation an attractive option. Achieving insulin independence in type 1 diabetes was the perceived goal of islet cell transplantation. The success of the Edmonton group in achieving this in a selected group of type 1 patients has led to renewed optimism that this treatment could eventually replace whole organ pancreas transplantation. However the long-term results of this treatment indicate that insulin independence is lost with time in a significant proportion of patients, although they may retain glycaemic stability. In this context, the indications for islet cell transplantation, which have evolved over the last 5 years, indicate that the patients who benefit most are those who experience severe hypoglycaemic reactions despite optimal insulin therapy. This review will summarise the history of islet cell transplantation, islet isolation techniques, the transplant procedure, immunosuppressive therapy, indications for islet cell transplantation, current clinical trials, the early UK islet cell transplant experience using the Edmonton protocol, and some of the challenges that lie ahead.
TRANSDERMAL ANAESTHESIA FOR PERCUTANEOUS TRIGGER FINGER RELEASE
Authors: Yiannakopoulos Christos K. , Ignatiadis Ioannis A. 
Published: April 2007

The purpose of this study was to evaluate the safety and efficiency of transdermal anaesthesia using eutectic mixture of lidocaine and prilocaine (EMLA) in patients undergoing percutaneous trigger finger release and to compare it with lidocaine infiltration. In this prospective, randomised study percutaneous release of the A1 annular pulley was performed to treat stenosing tenosynovitis (trigger finger syndrome) in 50 patients (50 fingers). The procedure was performed either under transdermal anaesthesia using EMLA applied transcutaneously 120 minutes prior to the operation (Group A, n = 25) or using local infiltration anaesthesia using lidocaine (Group B, n = 25). Pain experienced during administration of anaesthesia and during the operation was assessed using a 10-point Visual Analogue Pain Scale (VAPS), while all patients rated the effectiveness of anaesthesia with a 5-point scale. There were no significant differences between the two groups in the VAPS during the operation (1.33 ± 0.52 versus 1.59 ± 0.87) and the satisfaction scores (4.6 ± 0.2 versus 4.4 ± 0.3). The VAPS score during the administration of anaesthesia was statistically significantly less in the EMLA group (0 versus 5.96 ± 2.41). All patients were satisfied with the final result of the operation. Percutaneous trigger finger release can be performed as an office procedure with the use of EMLA avoiding the use of injectable local infiltration anaesthesia.
Selective Killing of Cancer Cells by Leaf Extract of Ashwagandha: Identification of a Tumor-Inhibitory Factor and the First Molecular Insights to Its Effect
Authors: Widodo Nashi , Kaur Kamaljit , Shrestha Bhupal G. , Takagi Yasuomi , Ishii Tetsuro , Wadhwa Renu , Kaul Sunil C. 
Published: April 2007

Abstract
Purpose: Ashwagandha is regarded as a wonder shrub of India and is commonly used in Ayurvedic medicine and health tonics that claim its variety of health-promoting effects. Surprisingly, these claims are not well supported by adequate studies, and the molecular mechanisms of its action remain largely unexplored to date. We undertook a study to identify and characterize the antitumor activity of the leaf extract of ashwagandha.
Experimental Design: Selective tumor-inhibitory activity of the leaf extract (i-Extract) was identified by in vivo tumor formation assays in nude mice and by in vitro growth assays of normal and human transformed cells. To investigate the cellular targets of i-Extract, we adopted a gene silencing approach using a selected small hairpin RNA library and found that p53 is required for the killing activity of i-Extract.
Results: By molecular analysis of p53 function in normal and a variety of tumor cells, we found that it is selectively activated in tumor cells, causing either their growth arrest or apoptosis. By fractionation, purification, and structural analysis of the i-Extract constituents, we have identified its p53-activating tumor-inhibiting factor as withanone.
Conclusion: We provide the first molecular evidence that the leaf extract of ashwagandha selectively kills tumor cells and, thus, is a natural source for safe anticancer medicine.
Preclinical Studies of TW-37, a New Nonpeptidic Small-Molecule Inhibitor of Bcl-2, in Diffuse Large Cell Lymphoma Xenograft Model Reveal Drug Action on Both Bcl-2 and Mcl-1
Authors: Mohammad Ramzi M. , Goustin Anton Scott , Aboukameel Amro , Chen Ben , Banerjee Sanjeev , Wang Guoping , Nikolovska-Coleska Zaneta , Wang Shaomeng , Al-Katib Ayad 
Published: April 2007

Abstract
Purpose: Overexpression of Bcl-2 protein has been observed in more than 80% of B-cell lymphomas, including diffuse large cell lymphoma (DLCL), the most common subtype of non-Hodgkin's lymphoma. We have previously employed the natural product (−)-gossypol to test its therapeutic potential as a small-molecule inhibitor of Bcl-2 for the treatment of B-cell lymphomas.
Experimental Design: Recently, we have used a structure-based strategy to design a new class of potent small-molecule inhibitor acting on Bcl-2. One such lead compound is the benzenesulfonyl derivative TW-37, which was designed to target the BH3-binding groove in Bcl-2 where proapoptotic Bcl-2 proteins, such as Bak, Bax, Bid, and Bim bind.
Results: In our fluorescence polarization–based binding assays using recombinant Bcl-2, Bcl-XL, and Mcl-1 proteins, TW-37 binds to Bcl-2, Bcl-XL, and Mcl-1 with Ki values of 290, 1,110 and 260 nmol/L, respectively. Hence, TW-37 is a potent inhibitor of Bcl-2 and has &gt;3-fold selectivity over Bcl-XL. In vitro, TW-37 showed significant antiproliferative effect in a de novo chemoresistant WSU-DLCL2 lymphoma cell line and primary cells obtained from a lymphoma patient with no effect on normal peripheral blood lymphocytes. Coimmunoprecipitation experiments showed that TW-37 disrupted heterodimer formation between Bax or truncated-Bid and antiapoptotic proteins in the order Mcl-1 &gt; Bcl-2 &gt;&gt; Bcl-XL. As expected, TW-37 caused apoptotic death. Pre-exposure of lymphoma cells to TW-37 significantly enhanced the killing effect of cyclophosphamide-doxorubicin-vincristine-prednisone (CHOP) regimen. The maximum tolerated dose of TW-37 in severe combined immunodeficient (SCID) mice was 40 mg/kg for three i.v. injections when given alone and 20 mg/kg, ×3 when given in combination with CHOP. Using WSU-DLCL2-SCID mouse xenograft model, the addition of TW-37 to CHOP resulted in more complete tumor inhibition compared with either CHOP or TW-37 alone.
Conclusions: We conclude that the administration of TW-37, as a potent Bcl-2 and Mcl-1 inhibitor, to standard chemotherapy may prove an effective strategy in the treatment of B-cell lymphoma.
Effects of the Administration of High-Dose Interleukin-2 on Immunoregulatory Cell Subsets in Patients with Advanced Melanoma and Renal Cell Cancer
Authors: van derVliet Hans J.J. , Koon Henry B. , Yue Simon C. , Uzunparmak Burak , Seery Virginia , Gavin Marc A. , Rudensky Alexander Y. , Atkins Michael B. , Balk Steven P. , Exley Mark A. 
Published: April 2007

AbstractPurpose: High-dose recombinant human interleukin-2 (IL-2) therapy is of clinical benefit in a subset of patients with advanced melanoma and renal cell cancer. Although IL-2 is well known as a T-cell growth factor, its potential in vivo effects on human immunoregulatory cell subsets are largely unexplored.Experimental Design: Here, we studied the effects of high-dose IL-2 therapy on circulating dendritic cell subsets (DC), CD1d-reactive invariant natural killer T cells (iNKT), and CD4+CD25+ regulatory-type T cells.Results: The frequency of both circulating myeloid DC1 and plasmacytoid DC decreased during high-dose IL-2 treatment. Of these, only a significant fraction of myeloid DC expressed CD1d. Although the proportion of Th1-type CD4− iNKT increased, similarly to DC subsets, the total frequency of iNKT decreased during high-dose IL-2 treatment. In contrast, the frequency of CD4+CD25+ T cells, including CD4+Foxp3+ T cells, which have been reported to suppress antitumor immune responses, increased during high-dose IL-2 therapy. However, there was little, if any, change of expression of GITR, CD30, or CTLA-4 on CD4+CD25+ T cells in response to IL-2. Functionally, patient CD25+ T cells at their peak level (immediately after the first cycle of high-dose IL-2) were less suppressive than healthy donor CD25+ T cells and mostly failed to Th2 polarize iNKT.Conclusions: Our data show that there are reciprocal quantitative and qualitative alterations of immunoregulatory cell subsets with opposing functions during treatment with high-dose IL-2, some of which may compromise the establishment of effective antitumor immune responses.
Systemic CTLA-4 Blockade Ameliorates Glioma-Induced Changes to the CD4+ T Cell Compartment without Affecting Regulatory T-Cell Function
Authors: Fecci Peter E. , Ochiai Hidenobu , Mitchell Duane A. , Grossi Peter M. , Sweeney Alison E. , Archer Gary E. , Cummings Thomas , Allison James P. , Bigner Darell D. , Sampson John H. 
Published: April 2007

AbstractPurpose: Patients with malignant glioma suffer global compromise of their cellular immunity, characterized by dramatic reductions in CD4+ T cell numbers and function. We have previously shown that increased regulatory T cell (Treg) fractions in these patients explain T-cell functional deficits. Our murine glioma model recapitulates these findings. Here, we investigate the effects of systemic CTLA-4 blockade in this model.Experimental Design: A monoclonal antibody (9H10) to CTLA-4 was employed against well-established glioma. Survival and risks for experimental allergic encephalomyelitis were assessed, as were CD4+ T cell numbers and function in the peripheral blood, spleen, and cervical lymph nodes. The specific capacities for anti-CTLA-4 to modify the functions of regulatory versus CD4+CD25− responder T cells were evaluated.Results: CTLA-4 blockade confers long-term survival in 80% of treated mice, without eliciting experimental allergic encephalomyelitis. Changes to the CD4 compartment were reversed, as anti-CTLA-4 reestablishes normal CD4 counts and abrogates increases in CD4+CD25+Foxp3+GITR+ regulatory T cell fraction observed in tumor-bearing mice. CD4+ T-cell proliferative capacity is restored and the cervical lymph node antitumor response is enhanced. Treatment benefits are bestowed exclusively on the CD4+CD25− T cell population and not Tregs, as CD4+CD25− T cells from treated mice show improved proliferative responses and resistance to Treg-mediated suppression, whereas Tregs from the same mice remain anergic and exhibit no restriction of their suppressive capacity.Conclusions: CTLA-4 blockade is a rational means of reversing glioma-induced changes to the CD4 compartment and enhancing antitumor immunity. These benefits were attained through the conferment of resistance to Treg-mediated suppression, and not through direct effects on Tregs.
Microtubule-Associated Protein-tau is a Bifunctional Predictor of Endocrine Sensitivity and Chemotherapy Resistance in Estrogen Receptor–Positive Breast Cancer
Authors: Andre Fabrice , Hatzis Christos , Anderson Keith , Sotiriou Christos , Mazouni Chafika , Mejia Jaime , Wang Bailiang , Hortobagyi Gabriel N. , Symmans W. Fraser , Pusztai Lajos 
Published: April 2007

Abstract
Purpose: The clinical outcome for patients with breast cancer is influenced by the metastatic competence of the cancer and its sensitivity to endocrine therapy and chemotherapy. A molecular marker may be prognostic of outcome or predictive of response to therapy, or a combination of both.
Experimental Design: We examined separately the prognostic and predictive values of tau mRNA expression in estrogen receptor (ER)–positive primary breast cancers in three patient cohorts. We used gene expression data from 209 untreated patients to assess the pure prognostic value of tau, data from 267 patients treated with adjuvant tamoxifen to assess predictive value for endocrine therapy, and data from 82 patients treated with preoperative paclitaxel followed by 5-fluorouracil, doxorubicin, and cyclophosphamide (paclitaxel/FAC) to assess predictive value for chemotherapy response. Wilcoxon rank sum test was used to compare tau expression between different outcome groups.
Results: Higher tau mRNA expression showed borderline nonsignificant association with better prognosis in the absence of systemic adjuvant therapy. Higher tau mRNA expression was significantly associated with no recurrence (at 5 and 10 years, P = 0.005 and P = 0.05, respectively) in patients treated with tamoxifen, indicating a predictive value for endocrine therapy. Tau expression was significantly lower in patients who achieved pathologic complete response to paclitaxel/FAC chemotherapy (P &lt; 0.001).
Conclusion: This study suggests that high tau mRNA expression in ER-positive breast cancer indicates an endocrine-sensitive but chemotherapy-resistant disease. In contrast, low tau expression identifies a subset of ER-positive cancers that have poor prognosis with tamoxifen alone and may benefit from taxane-containing chemotherapy.
The Potential of Antiangiogenic Therapy in Non–Small Cell Lung Cancer
Authors: Giaccone Giuseppe 
Published: April 2007

AbstractThe long-term prognosis for patients with advanced non–small cell lung cancer (NSCLC) remains poor despite the availability of several cytotoxic chemotherapy regimens. The use of targeted therapies, particularly those against the key mediator of angiogenesis vascular endothelial growth factor (VEGF), has the potential to improve outcomes for NSCLC patients. Bevacizumab, a recombinant humanized monoclonal anti-VEGF antibody, is the most clinically advanced antiangiogenic agent in NSCLC. In a phase III study, bevacizumab showed significantly improved overall and progression-free survival when used in combination with standard first-line chemotherapy in patients with advanced NSCLC. Bevacizumab was generally well tolerated in patients with NSCLC; however, tumor-related bleeding adverse events have been noted in some patients, predominantly those with squamous cell histology or centrally located tumors. Several small-molecule VEGF receptor tyrosine kinase inhibitors have also shown promise in phase I and II trials in NSCLC. This review summarizes the most important findings of angiogenesis inhibitors in NSCLC and discusses the potential for the use of these novel agents in different settings of NSCLC.
Population-Based Molecular Prognosis of Breast Cancer by Transcriptional Profiling
Authors: Ma Yan , Qian Yong , Wei Liang , Abraham Jame , Shi Xianglin , Castranova Vincent , Harner E. James , Flynn Daniel C. , Guo Lan 
Published: April 2007

Abstract
Purpose: The purpose of this study is to predict breast cancer recurrence and metastases and to identify gene signatures indicative of clinicopathologic characteristics using gene expression patterns derived from cDNA microarray.
Experimental Design: Expression profiles of 7,650 genes were investigated on an unselected group of 99 node-negative and node-positive breast cancer patients to identify prognostic gene signature of recurrence and metastases. The identified gene signature was validated on independent 78 patients with primary invasive carcinoma (T1/T2 and N0) and on 58 patients with locally advanced breast cancer (T3/T4 and/or N2). The gene predictors were identified using a combination of random forests and linear discriminant analysis function.
Results: This study identified a new 28-gene signature that achieved highly accurate disease-free survival and overall survival (both at P &lt; 0.001, time-dependent receiver operating characteristic analysis) in individual breast cancer patients. Patients categorized into high-risk, intermediate-risk, and low-risk groups had distinct disease-free survival (P &lt; 0.005, Kaplan-Meier analysis, log-rank test) in three patient cohorts. A strong association (P &lt; 0.05) was identified between risk groups and tumor size, tumor grade, estrogen receptor and progesterone receptor status, and HER2/neu overexpression in the studied cohorts. We also identified 14-gene predictors of nodal status and 9-gene predictors of tumor grade.
Conclusions: This study has established a population-based approach to predicting breast cancer outcomes at the individual level exclusively based on gene expression patterns. The 28-gene recurrence signature has been validated as quantifying the probability of recurrence and metastases in patients with heterogeneous histology and disease stage.
Evaluation of Plasma Insulin-like Growth Factor Binding Protein 2 and Her-2 Extracellular Domain as Biomarkers for 17-Allylamino-17-Demethoxygeldanamycin Treatment of Adult Patients with Advanced Solid Tumors
Authors: Eiseman Julie L. , Guo Jianxia , Ramanathan Ramesh K. , Belani Chandra P. , Solit David B. , Scher Howard I. , Ivy S. Percy , Zuhowski Eleanor G. , Egorin Merrill J. 
Published: April 2007

Abstract
Purpose: Interaction of 17-allylamino-17-demethoxygeldanamycin (17-AAG) with heat shock protein 90 results in proteasomal degradation of many proteins, including Her-2-neu, with subsequent decreased expression of insulin-like growth factor binding protein-2 (IGFBP-2). Concentrations of both IGFBP-2 and Her-2 extracellular domain (Her-2 ECD) in sera of mice bearing BT474 human breast cancer xenografts decrease after 17-AAG treatment. We investigated whether this phenomenon occurred in patients.
Materials and Methods: Eight to 15 plasma samples were obtained between 0 and 72 h from 27 patients treated with single-agent 17-AAG at doses between 10 and 307 mg/m2 and 18 patients treated with 17-AAG at doses between 220 and 450 mg/m2 combined with 70 to 75 mg/m2 of docetaxel. Pretreatment plasma samples were also obtained from 12 healthy volunteers. Plasma IGFBP-2 and Her-2 ECD concentrations were quantitated by ELISA.
Results: Pretreatment plasma IGFBP-2 concentrations in patients (171 ± 116 ng/mL) were 2-fold higher than those in healthy volunteers (85 ± 44 ng/mL; P &lt; 0.05). Following 17-AAG treatment, there were no consistent dose-dependent or time-dependent changes in plasma IGFBP-2 and Her-2 ECD concentrations. IGFBP-2 concentrations decreased by ≥40% in 8 patients, increased 2- to 5-fold in 8 patients, and remained essentially unchanged in 29 patients. Her-2 ECD concentrations decreased by ≥40% in 10 patients, increased 1.5- to 5-fold in 2 patients, and remained essentially unchanged in 25 patients.
Conclusions: As previously reported, IGFBP-2 concentrations in plasma of cancer patients are significantly higher than those in healthy volunteers. In contrast to a mouse model, 17-AAG treatment was not consistently associated with decreases in IGFBP-2 or Her-2 ECD concentrations in patient plasma.
Adrenal Androgen Levels as Predictors of Outcome in Prostate Cancer Patients Treated with Ketoconazole Plus Antiandrogen Withdrawal: Results from a Cancer and Leukemia Group B Study
Authors: Ryan Charles J. , Halabi Susan , Ou San-San , Vogelzang Nicholas J. , Kantoff Philip , Small Eric J. ,   for the Cancer and Leukemia Group B
Published: April 2007

Abstract
Purpose: Adrenal androgens activate the androgen receptor and stimulate prostate cancer growth. Ketoconazole is used as an inhibitor of adrenal androgen synthesis in men with androgen-independent prostate cancer. This study analyzes the relationship between pretreatment androgen levels and outcome following ketoconazole treatment.
Experimental Design: Baseline levels of three adrenal androgens (androstenedione, dehydroepiandrostenedione, and dehydroepiandrostenedione-sulfate) and testosterone were measured. Regression models (logistic and proportional hazard) were used to assess the prognostic significance of these levels in predicting overall survival and prostate-specific antigen (PSA) response defined by Consensus Criteria.
Results: In 103 patients with available levels, PSA response rate was 28% and median response duration was 4.8 months. The median baseline androstenedione level was 0.64 ng/mL and was 0.88 ng/mL versus 0.53 ng/mL for those with and without a PSA response, respectively (P = 0.034). In univariate analysis, elevation of baseline androstenedione levels was predictive of PSA response [odds ratio, 2.26; 95% confidence interval (95% CI), 1.03-4.96; P = 0.043]. In multivariate analysis, both the uppermost and the middle tertile of baseline androstenedione level were associated with an improved overall survival compared with those in the lower tertile (hazard ratio, 0.59; 95% CI, 0.36-0.98; P = 0.40; hazard ratio, 0.53; 95% CI, 0.32-0.90; P = 0.018, respectively). A linear correlation was observed among all androgen levels.
Conclusions: Higher androstenedione levels predict likelihood of response to ketoconazole and improved survival compared with patients with lower levels. These data suggest that therapy with ketoconazole is less effective in patients with low levels of androgen at baseline.