tbuckley/cabot-search huggingface dataset:
Randomized Study of Basal-Bolus Insulin Therapy in the Inpatient Management of Patients With Type 2 Diabetes Undergoing General Surgery (RABBIT 2 Surgery)
Authors: Guillermo E. Umpierrez, Dawn Smiley, Sol Jacobs, Limin Peng, Angel Temponi, Patrick Mulligan, Denise Umpierrez, Christopher Newton, Darin Olson, Monica Rizzo
Journal: Diabetes Care (2011)

The optimal treatment of hyperglycemia in general surgical patients with type 2 diabetes mellitus is not known.This randomized multicenter trial compared the safety and efficacy of a basal-bolus insulin regimen with glargine once daily and glulisine before meals (n = 104) to sliding scale regular insulin (SSI) four times daily (n = 107) in patients with type 2 diabetes mellitus undergoing general surgery. Outcomes included differences in daily blood glucose (BG) and a composite of postoperative complications including wound infection, pneumonia, bacteremia, and respiratory and acute renal failure.The mean daily glucose concentration after the 1st day of basal-bolus insulin and SSI was 145 ± 32 mg/dL and 172 ± 47 mg/dL, respectively (P < 0.01). Glucose readings <140 mg/dL were recorded in 55% of patients in basal-bolus and 31% in the SSI group (P < 0.001). There were reductions with basal-bolus as compared with SSI in the composite outcome [24.3 and 8.6%; odds ratio 3.39 (95% CI 1.50-7.65); P = 0.003]. Glucose <70 mg/dL was reported in 23.1% of patients in the basal-bolus group and 4.7% in the SSI group (P < 0.001), but there were no significant differences in the frequency of BG <40 mg/dL between groups (P = 0.057).Basal-bolus treatment with glargine once daily plus glulisine before meals improved glycemic control and reduced hospital complications compared with SSI in general surgery patients. Our study indicates that a basal-bolus insulin regimen is preferred over SSI in the hospital management of general surgery patients with type 2 diabetes.
International Union of Pharmacology XXXVII. Nomenclature for Leukotriene and Lipoxin Receptors
Authors: Charles Brink, Sven-Erik Dahlén, Jeffrey Drazen, Jilly F. Evans, Douglas W. P. Hay, Simonetta Nicosia, Charles N. Serhan, Takao Shimizu, Takehiko Yokomizo
Journal: Pharmacological Reviews (2003)

The leukotrienes and lipoxins are biologically active metabolites derived from arachidonic acid. Their diverse and potent actions are associated with specific receptors. Recent molecular techniques have established the nucleotide and amino acid sequences and confirmed the evidence that suggested the existence of different G-protein-coupled receptors for these lipid mediators. The nomenclature for these receptors has now been established for the leukotrienes. BLT receptors are activated by leukotriene B<sub>4</sub> and related hydroxyacids and this class of receptors can be subdivided into BLT<sub>1</sub> and BLT<sub>2</sub>. The cysteinyl-leukotrienes (LT) activate another group called CysLT receptors, which are referred to as CysLT<sub>1</sub> and CysLT<sub>2</sub>. A provisional nomenclature for the lipoxin receptor has also been proposed. LXA<sub>4</sub> and LXB<sub>4</sub> activate the ALX receptor and LXB<sub>4</sub> may also activate another putative receptor. However this latter receptor has not been cloned. The aim of this review is to provide the molecular evidence as well as the properties and significance of the leukotriene and lipoxin receptors, which has lead to the present nomenclature.
Neoadjuvant Chemotherapy With Doxorubicin and Cisplatin in Malignant Fibrous Histiocytoma of Bone: A European Osteosarcoma Intergroup Study
Authors: Vivien H.C. Bramwell, William P. Steward, Marianne Nooij, Jeremy Whelan, Alan W. Craft, Robert J. Grimer, Antonie H.M. Taminau, Steven R. Cannon, Archie J. Malcolm, Pancras C.W. Hogendoorn, Barbara Uscinska, Anne L. Kirkpatrick, David Machin, Martine M. Van Glabbeke
Journal: Journal of Clinical Oncology (1999)

PURPOSE: Studies involving small case series have suggested that malignant fibrous histiocytoma of bone (MFH-B) is a chemosensitive tumor and that chemotherapy may improve survival. In this study, we evaluated clinical and pathologic response rates and survival in a series of patients treated with a consistent chemotherapy regimen of doxorubicin and cisplatin (DOX/DDP). PATIENTS AND METHODS: Study patients were required to have biopsy-proven MFH-B, no previous chemotherapy, and primary or metastatic measurable disease and to be ≤ 65 years of age. Treatment consisted of doxorubicin 25 mg/m 2 /d days 1 through 3 and cisplatin 100 mg/m 2 by 4-hour intravenous infusion every 3 weeks for six cycles. In patients with operable primary tumors, chemotherapy was planned to start within 42 days of biopsy, with definitive surgery performed after three cycles. RESULTS: Forty-one patients had operable nonmetastatic limb sarcomas, and 23 (56%) completed six chemotherapy cycles. Limb salvage was possible in 33 patients (80%), and 16 (42%) of 38 assessable specimens showed a good pathologic response (≥ 90% necrosis). Median time to progression was 56 months, and the 5-year progression-free survival rate was 56% (95% confidence interval [CI], 40% to 72%). Median survival time was 63 months, and the 5-year survival rate was 59% (95% CI, 41% to 77%). Patients with a good pathologic response had longer survival times and times to progression than did those with a poor response. Also treated were two patients with locally recurrent and nine with metastatic disease, and these patients had a median survival time of 17.5 months. CONCLUSION: Our study suggests that adjuvant or neoadjuvant chemotherapy with DOX/DDP is beneficial in MFH-B. Good pathologic response rates and survivals are quite comparable with those for osteosarcoma, a related bone tumor for which adjuvant or neoadjuvant chemotherapy is an accepted practice.
Implications of the Prostate Cancer Prevention Trial: A Decision Analysis Model of Survival Outcomes
Authors: Yair Lotan, Jeffrey A. Cadeddu, J. Jack Lee, Claus G. Roehrborn, Scott M. Lippman
Journal: Journal of Clinical Oncology (2005)

To assess the estimated effect of finasteride prevention of prostate cancer on overall survival.Data for our decision tree model came from men in the two arms (finasteride or placebo) of the Prostate Cancer Prevention Trial (PCPT) and from clinically localized prostate cancer patients studied for long-term survival outcomes. Our model compared survival outcomes for men treated with finasteride or placebo. Prostate cancer rates were based on the 7-year period prevalence of prostate cancer detected in the PCPT; survival probabilities were abstracted from the long-term outcome studies. We assessed variability in the PCPT and long-term survival studies to test the variability of our model.Survival advantages for a finasteride-treated (v those not treated with finasteride) population include gains of 1.7 months in 15-year cause-specific survival (assuming finasteride-altered Gleason scores and prostate cancer prevalence rates in the PCPT), of up to 3 months for cancers treated conservatively or surgically (assuming finasteride does not alter Gleason scores), and of 0.35 months (assuming the rate of cancers detected by for-cause biopsies in the PCPT), which increased to 1.7 months when assuming a 30% rate of biopsy-detected cancer in the PCPT placebo group. Model-variability analyses support several survival benefits associated with finasteride (eg, the uniform benefits assuming finasteride does not alter Gleason scores) but question certain others (eg, in 15-year recurrence-free survivals assuming finasteride does alter Gleason scores).Finasteride can impart survival benefits according to our model, especially when we assume that finasteride does not alter Gleason scores.
Metabolic Approach to the Enhancement of Antitumor Effect of Chemotherapy: a Key Role of Acetyl-<scp>l</scp>-Carnitine
Authors: Claudio Pisano, Loredana Vesci, Ferdinando Maria Milazzo, Mario Berardino Guglielmi, Rosanna Foderà, Marcella Barbarino, Maurizio D'Incalci, Massimo Zucchetti, Giovanna Petrangolini, Monica Tortoreto, Paola Perego, Valentina Zuco, Augusto Orlandi, Daniela Passeri, Paolo Carminati, Claudio Cavazza, Franco Zunino
Journal: Clinical Cancer Research (2010)

Acetyl-L-carnitine (ALC) plays a relevant role in energy metabolism and stress response because of its function in the complex metabolic system regulating the acetyl-CoA levels that provide a source of acetyl groups for metabolic and acetylation-regulated processes. Because acetylation may influence p53 activity/stability and, therefore, the response to platinum compounds, this study was designed to investigate the effect of ALC in combination with platinum compounds.The antiproliferative and antitumor activity studies were done in a panel of human tumor cell lines with functional or defective p53. The antimetastatic drug efficacy was investigated in the s.c. growing H460/M tumor subline, which is able to generate lung metastases.ALC enhanced the sensitivity to cisplatin of tumor cells with functional p53. The sensitization by ALC was reflected in an improved in vivo antitumor efficacy of the combination over cisplatin alone in wild-type p53 lung tumors. ALC did not increase the cisplatin efficacy in the p53-mutant SW620 tumor. ALC exhibited a significant antimetastatic activity, and this effect was better exploited in combination with the histone deacetylase inhibitor, ST3595. The in vivo ALC/cisplatin combination caused the activation of p53, associated with protein acetylation and induction of target genes.ALC was effective in enhancing the antitumor potential of platinum compounds in wild-type p53 tumors. ALC, alone and in combination with a histone deacetylase inhibitor, exhibited an outstanding antimetastatic activity. Both effects, likely mediated by protein acetylation, may have implications for platinum-based therapy and combinations with histone deacetylase inhibitors.
Prophylactic antibiotics after acute stroke for reducing pneumonia in patients with dysphagia (STROKE-INF): a prospective, cluster-randomised, open-label, masked endpoint, controlled clinical trial
Authors: Lalit Kalra, Saddif Irshad, John Hodsoll, Matthew Simpson, Martin Gulliford, David Smithard, Anita Patel, Irene Rebollo-Mesa
Journal: The Lancet (2015)
Association of Methylphenidate-Induced Craving With Changes in Right Striato-orbitofrontal Metabolism in Cocaine Abusers: Implications in Addiction
Authors: Nora D. Volkow, Gene-Jack Wang, Joanna S. Fowler, Robert Hitzemann, Burton Angrist, Samuel J. Gatley, Jean Logan, Yu-Shin Ding, Naomi Pappas
Journal: American Journal of Psychiatry (1999)

The authors have shown that decreases in dopamine D2 receptors in cocaine abusers were associated with decreased metabolism in the cingulate and prefrontal and orbitofrontal cortices. To assess whether increasing dopamine would reverse these metabolic decrements, they measured the effects of methylphenidate, a drug that increases dopamine, on brain glucose metabolism in 20 cocaine abusers.The subjects underwent two [18F]fluorodeoxyglucose positron emission tomography scans, one after two sequential placebo injections and one after two intravenous doses of methylphenidate. D2 receptors were measured with [11C]raclopride to evaluate their relation to methylphenidate-induced metabolic changes.Methylphenidate induced variable changes in brain metabolism: subjects with the higher D2 measures tended to increase metabolism, whereas those with the lower D2 measures tended to decrease metabolism. Methylphenidate's effects were significant for increases in metabolism in the superior cingulate, right thalamus, and cerebellum. Methylphenidate-induced changes in the right orbitofrontal cortex and right striatum were associated with craving, and those in the prefrontal cortex were associated with mood.Although methylphenidate increased metabolism in the superior cingulate, it only increased metabolism in orbitofrontal or prefrontal cortices in the subjects in whom it enhanced craving and mood, respectively. This indicates that dopamine enhancement is not sufficient per se to increase metabolism in these frontal regions. Activation of the right orbitofrontal cortex and right striatum (brain regions found to be abnormal in compulsive disorders) in the subjects reporting craving may be one of the mechanisms underlying compulsive drug administration in addicted persons. The predominant correlation of craving with right but not left brain regions suggests laterality of reinforcing and/or conditioned responses.
New Strategies for Treatment of KRAS Mutant Metastatic Colorectal Cancer
Authors: Hans Prenen, Sabine Tejpar, Eric Van Cutsem
Journal: Clinical Cancer Research (2010)

The introduction of new cytotoxic agents and new targeted therapies has significantly broadened the therapeutic options for and the outcomes of patients with metastatic colorectal cancer (CRC). The introduction of the anti-epidermal growth factor receptor (EGFR) antibodies, cetuximab and panitumumab, has clearly contributed to this development. The concept of KRAS as a marker for resistance to anti-EGFR antibodies has been validated. However, new challenges have emerged: the complete understanding of the crucial and central role of KRAS in processes of tumor growth and the development of new treatment strategies for KRAS mutant tumors. KRAS seems to be so crucial that a further classification and description in KRAS wild-type and mutant may be warranted. Testing for KRAS mutations marks, therefore, a paradigm shift in the management of metastatic CRC. This testing also highlights the unmet need for new treatment options in KRAS mutant metastatic CRC. In this review we will focus on possible new treatment options for these patients.
MTDH-SND1 Interaction Is Crucial for Expansion and Activity of Tumor-Initiating Cells in Diverse Oncogene- and Carcinogen-Induced Mammary Tumors
Authors: Liling Wan, Xin Lu, Salina Yuan, Yong Wei, Feng Guo, Minhong Shen, Min Yuan, Rumela Chakrabarti, Yuling Hua, Heath A. Smith, Mario Andres Blanco, Marina Chekmareva, Hao Wu, Roderick T. Bronson, Bruce G. Haffty, Yongna Xing, Yibin Kang
Journal: Cancer Cell (2014)
Peripheral Arterial Disease and Risk of Cardiac Death in Type 2 Diabetes
Authors: Paul E. Norman, Wendy A. Davis, David G. Bruce, Timothy M.E. Davis
Journal: Diabetes Care (2006)

OBJECTIVE—The purpose of this study was to examine the natural history of peripheral arterial disease (PAD) complicating type 2 diabetes, in particular the influence of PAD on the risk of cardiac death and the adequacy of PAD risk factor management. RESEARCH DESIGN AND METHODS—The Fremantle Diabetes Study (FDS) was a prospective community-based observational study of diabetic patients recruited between 1993 and 1996. The present sample comprised the 1,294 FDS type 2 diabetic patients and a subgroup of 531 of these who had valid data at baseline and five or more subsequent consecutive annual reviews. Assessments consisted of a range of clinical and biochemical variables including the ankle/brachial index (ABI). PAD was defined as an ABI ≤0.90 at two consecutive reviews or any PAD-related lower-extremity amputation. RESULTS—The prevalence of PAD at study entry was 13.6% and the incidence of new PAD was 3.7 per 100 patient-years. Both prevalent and incident PAD was strongly and independently associated with increasing age, systolic blood pressure, total serum cholesterol, and especially smoking. Risk factor management improved but remained suboptimal during follow-up. An ABI of ≤0.90 was independently associated with an increased risk of cardiac death of 67%. CONCLUSIONS—Measurement of the ABI is a simple means of identifying PAD in diabetic patients. PAD is common in diabetic patients and predicts cardiac death. These data further support the role of regular screening for PAD in diabetes so that intensive management of vascular risk factors can be pursued.
Membranous Expression of Secreted Frizzled-Related Protein 4 Predicts for Good Prognosis in Localized Prostate Cancer and Inhibits PC3 Cellular Proliferation <b> <i>in Vitro</i> </b>
Authors: Lisa G. Horvath, Susan M. Henshall, James G. Kench, Darren N. Saunders, C.-Soon Lee, David Golovsky, Phillip C. Brenner, Gordon F. O’Neill, Raji Kooner, Phillip D. Stricker, John J. Grygiel, Robert L. Sutherland
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Activation of the Wnt-signaling pathway is implicated in aberrant cellular proliferation in a variety of cancers. Secreted frizzled-related protein 4 (sFRP4) is a secreted protein with putative inhibitory activity of the Wnt-signaling cascade through binding and sequestering Wnt ligands. Because sFRP4 mRNA is overexpressed in prostate cancers (PCs), the aim of this study was to define the pattern of sFRP4 protein expression in normal and malignant human prostate tissue and to determine whether changes in expression were associated with disease progression and prognosis, as well as to define the phenotype of sFRP4-overexpression in an in vitro model of PC. Experimental Design: Polyclonal antibodies were raised against a COOH-terminal peptide of sFRP4, characterized and used to assess sFRP4 protein expression in benign prostate tissue and 229 patients with clinically localized PC (median follow-up 77 months, range 1–156). In vitro studies of the function of sFRP4 overexpression were performed using PC3 cells transfected with sFRP4. Results: Benign and malignant prostate tissue demonstrated cytoplasmic sFRP4 immunoreactivity, but there was a decrease in the expression of membranous sFRP4 in PCs compared with the hyperplastic lesions (P &amp;lt; 0.0001). Kaplan-Meier analysis revealed that patients whose PC expressed membranous sFRP4 in &amp;gt;20% of cells had improved relapse-free survival compared with those with ≤20% membranous expression (P = 0.002). Moreover, membranous sFRP4 expression (P = 0.04) was an independent predictor of relapse when modeled with Gleason score (P = 0.006), pathological stage (P = 0.002), and pre-operative prostate-specific antigen levels (P = 0.004). In addition, in vitro studies demonstrated a decrease in the proliferation rate of PC3 cells transfected with sFRP4 when compared with the control PC3-empty vector cells (P &amp;lt; 0.0001). Decreased levels of phosphorylated glycogen synthase kinase 3β in PC3-sFRP4 cells suggested that this phenotype is mediated by the “Wnt/β-catenin” pathway. Conclusions: These data suggest that sFRP4 expression may be prognostic for localized PC, potentially as a consequence of an inhibitory effect on PC cell proliferation.
Relationship Between Cingulo-Insular Functional Connectivity and Autistic Traits in Neurotypical Adults
Authors: Adriana Di Martino, Zarrar Shehzad, Clare Kelly, Amy Krain Roy, Dylan G. Gee, Lucina Q. Uddin, Kristin Gotimer, Donald F. Klein, F. Xavier Castellanos, Michael P. Milham
Journal: American Journal of Psychiatry (2009)

The Social Responsiveness Scale-Adult Version (SRS-A) measures autistic traits that are continuously distributed in the general population. Based on increased recognition of the dimensional nature of autistic traits, the authors examined the neural correlates of these traits in neurotypical individuals using the SRS-A and established a novel approach to assessing the neural basis of autistic characteristics, attempting to directly relate SRS-A scores to patterns of functional connectivity observed in the pregenual anterior cingulate cortex, a region commonly implicated in social cognition.Resting state functional magnetic resonance imaging scans were collected for 25 neurotypical adults. All participants provided SRS-A ratings completed by an informant who had observed them in natural social settings. Whole brain-corrected connectivity analyses were then conducted using SRS-A scores as a covariate of interest.Across participants, a significant negative relationship between SRS-A scores and the functional connectivity of the pregenual anterior cingulate cortex with the anterior portion of the mid-insula was found. Specifically, low levels of autistic traits were observed when a substantial portion of the anterior mid-insula showed positive connectivity with the pregenual anterior cingulate cortex. In contrast, elevated levels of autistic traits were associated with negative connectivity between these two regions.Resting state functional connectivity of the pregenual anterior cingulate cortex-insula social network was related to autistic traits in neurotypical adults. Application of this approach in samples with autism spectrum disorders is needed to confirm whether this circuit is dimensionally related to the severity of autistic traits in clinical populations.
Tedizolid for 6 days versus linezolid for 10 days for acute bacterial skin and skin-structure infections (ESTABLISH-2): a randomised, double-blind, phase 3, non-inferiority trial
Authors: Gregory J Moran, Edward Fang, G Ralph Corey, Anita F Das, Carisa De Anda, Philippe Prokocimer
Journal: The Lancet Infectious Diseases (2014)
Immune modulating effects of cyclophosphamide and treatment with tumor lysate/CpG synergize to eliminate murine neuroblastoma
Authors: Jill A. Gershan, Kristen M. Barr, James J. Weber, Weiqing Jing, Bryon D. Johnson
Journal: Journal for ImmunoTherapy of Cancer (2015)

Neuroblastoma is a pediatric cancer of neural crest origin. Despite aggressive treatment, mortality remains at 40 % for patients with high-risk disseminated disease, underscoring the need to test new combinations of therapies. In murine tumor models, our laboratory previously showed that T cell-mediated anti-tumor immune responses improve in the context of lymphopenia. The goal of this study was to incorporate lymphodepletion into an effective immune therapy that can be easily translated into neuroblastoma standard of care. Based on the lymphodepleting effects of cyclophosphamide, we hypothesized that cyclophosphamide would synergize with the TLR9 agonist, CpG oligodeoxynucleotide (ODN), to produce a T cell-mediated anti-neuroblastoma effect.To test this hypothesis, we used the AgN2a aggressive murine model of neuroblastoma. Mice bearing subcutaneous tumors were treated with cyclophosphamide followed by treatment with tumor cell lysate mixed with CpG ODN injected at the tumor site.Subcutaneous neuroblastoma regressed only in mice that were treated with 100 mg/kg cyclophosphamide prior to receiving treatments of tumor lysate mixed with CpG ODN. The anti-neuroblastoma response was T cell-mediated. Synergy between cyclophosphamide and the tumor lysate/CpG ODN treatment influenced the production of anti-tumor CD8 T cell effectors, and dendritic cell homeostasis. For clinical consideration, an allogeneic tumor lysate was used effectively with this protocol to eliminate AgN2a tumor in vivo.Synergistic immune modulating effects of cyclophosphamide and a treatment containing tumor cell lysate and CpG ODN provide T cell-mediated anti-tumor activity against murine neuroblastoma.
Osteoarthrosis in runners with knee pain.
Authors: M. McDermott, P. Freyne
Journal: British Journal of Sports Medicine (1983)

A clinical and radiological study of the knee joints of twenty middle and long distance runners, complaining of knee pain, was carried out. Osteoarthrosis of varying degree was found in six of the runners. A torn meniscus requiring surgery was found in one athlete, and another had considerable ligamentous laxity - both of these conditions predispose to the development of degenerative changes. Degenerative changes were significantly associated with the presence of genu varum (p less than 0.01) and history of severe injury (p less than 0.05). The number of years spent training was significantly greater in the affected group than in the unaffected group (p less than 0.05).
Comparative effectiveness of less commonly used systemic monotherapies and common combination therapies for moderate to severe psoriasis in the clinical setting
Authors: Junko Takeshita, Shuwei Wang, Daniel B. Shin, Kristina Callis Duffin, Gerald G. Krueger, Robert E. Kalb, Jamie D. Weisman, Brian R. Sperber, Michael B. Stierstorfer, Bruce A. Brod, Stephen M. Schleicher, Andrew D. Robertson, Kristin A. Linn, Russell T. Shinohara, Andrea B. Troxel, Abby S. Van Voorhees, Joel M. Gelfand
Journal: Journal of the American Academy of Dermatology (2014)