tbuckley/cabot-search huggingface dataset:
The subtype 2 (AT2) angiotensin receptor mediates renal production of nitric oxide in conscious rats.
Authors: H M Siragy, R M Carey
Journal: Journal of Clinical Investigation (1997)

The angiotensin AT2 receptor modulates renal production of cyclic guanosine 3',5'-monophosphate (cGMP; J. Clin. Invest. 1996. 97:1978-1982). In the present study, we hypothesized that angiotensin II (Ang II) acts at the AT2 receptor to stimulate renal production of nitric oxide leading to the previously observed increase in cGMP. Using a microdialysis technique, we monitored changes in renal interstitial fluid (RIF) cGMP in response to intravenous infusion of the AT2 receptor antagonist PD 123319 (PD), the AT1 receptor antagonist Losartan, the nitric oxide synthase (NOS) inhibitor nitro--arginine-methyl-ester (-NAME), the specific neural NOS inhibitor 7-nitroindazole (7-NI), or Ang II individually or combined in conscious rats during low or normal sodium balance. Sodium depletion significantly increased RIF cGMP. During sodium depletion, both PD and -NAME caused a similar decrease in RIF cGMP. Combined administration of PD and -NAME decreased RIF cGMP to levels observed with PD or -NAME alone or during normal sodium intake. During normal sodium intake, Ang II caused a twofold increase in RIF cGMP. Neither PD nor -NAME, individually or combined, changed RIF cGMP. Combined administration of Ang II and either PD or -NAME produced a significant decrease in RIF cGMP compared with that induced by Ang II alone. Combined administration of Ang II, PD, and -NAME blocked the increase in RIF cGMP produced by Ang II alone. During sodium depletion, 7-NI decreased RIF cGMP, but the reduction of cGMP in response to PD alone or PD combined with 7-NI was greater than with 7-NI alone. During normal sodium intake, 7-NI blocked the Ang II-induced increase in RIF cGMP. PD alone or combined with 7-NI produced a greater inhibition of cGMP than did 7-NI alone. During sodium depletion, 7-NI (partially) and -NAME (completely) inhibited RIF cGMP responses to -arginine. These data demonstrate that activation of the renin- angiotensin system during sodium depletion increases renal nitric oxide production through stimulation by Ang II at the angiotensin AT2 receptor. This response is partially mediated by neural NOS, but other NOS isoforms also contribute to nitric oxide production by this pathway.
P15.01 * WOUND HEALING COMPLICATIONS IN BRAIN TUMOR PATIENTS ON BEVACIZUMAB
Authors: H. Ladha, T. Pawar, M. R. Gilbert, T. S. Armstrong
Journal: Neuro-Oncology (2014)

Bevacizumab (BV) is a monoclonal antibody against vascular endothelial growth factor A (VEGF-A) and is commonly used for treatment of recurrent glioblastoma (GBM). Wound healing problems are a well-established adverse event, which may be compounded by the concomitant use of corticosteroids. Here, we present two patients with GBM who developed wound healing complications while on chronic corticosteroids following BV treatment. Case 1: 61-year-old male diagnosed with a right frontal GBM in 2009. He was initially treated with standard chemoradiation. At first recurrence, he participated in a trial with cediranib and on second recurrence was started treatment with dexamethasone 4mg daily and BV 10 mg/kg every 2 weeks. After the 31st cycle of BV, he had trauma to left hand with significant bruising and tearing of skin after hitting his hand against a stair railing. Wound continued to expand and developed secondary infection requiring antibiotics (Abx) and debridement. BV was discontinued and wound slowly healed over period of 3 months. Case 2: 29-year-old male diagnosed with a right frontal anaplastic glioma. Initial treatment was external beam radiation and then temozolomide at recurrence 1 year later. A second focus of tumor was found in the cerebellum 3 years later and was treated with XRT requiring the use of chronic corticosteroids. During third recurrence, treatment started with BV 10 mg/kg every 2 weeks and continuation of corticosteroids. After 3 months of treatment with BV, existing abdominal striae that had developed from weight gain dehisced, resulting in a secondary infection with MRSA. Despite local wound care and Abx, the areas did not heal, and patient succumbed to the infection 2 months later. While post-surgical wound healing problems are well known issues with BV use, these cases demonstrate uncommon wound healing adverse events in patients on chronic corticosteroids treated with BV. Clinicians should be aware of the potential for these adverse events and future studies addressing wound care strategies are needed to help prevent this potentially serious complication.
Treatment of Diabetic Ketoacidosis With Subcutaneous Insulin Aspart
Authors: Guillermo E. Umpierrez, Ruben Cuervo, Ana Karabell, Kashif Latif, Amado X. Freire, Abbas E. Kitabchi
Journal: Diabetes Care (2004)

OBJECTIVE—In this prospective, randomized, open trial, we compared the efficacy and safety of aspart insulin given subcutaneously at different time intervals to a standard low-dose intravenous (IV) infusion protocol of regular insulin in patients with uncomplicated diabetic ketoacidosis (DKA). RESEARCH DESIGN AND METHODS—A total of 45 consecutive patients admitted with DKA were randomly assigned to receive subcutaneous (SC) aspart insulin every hour (SC-1h, n = 15) or every 2 h (SC-2h, n = 15) or to receive IV infusion of regular insulin (n = 15). Response to medical therapy was evaluated by assessing the duration of treatment until resolution of hyperglycemia and ketoacidosis. Additional end points included total length of hospitalization, amount of insulin administration until resolution of hyperglycemia and ketoacidosis, and number of hypoglycemic events. RESULTS—Admission biochemical parameters in patients treated with SC-1h (glucose: 44 ± 21 mmol/l [means ± SD], bicarbonate: 7.1 ± 3 mmol/l, pH: 7.14 ± 0.09) were similar to those treated with SC-2h (glucose: 42 ± 21 mmol/l, bicarbonate: 7.6 ± 4 mmol/l, pH: 7.15 ± 0.12) and IV regular insulin (glucose: 40 ± 13 mmol/l, bicarbonate 7.1 ± 4 mmol/l, pH: 7.11 ± 0.17). There were no statistical differences in the mean duration of treatment until correction of hyperglycemia (6.9 ± 4, 6.1 ± 4, and 7.1 ± 5 h) or until resolution of ketoacidosis (10 ± 3, 10.7 ± 3, and 11 ± 3 h) among patients treated with SC-1h and SC-2h or with IV insulin, respectively (NS). There was no mortality and no differences in the length of hospital stay, total amount of insulin administration until resolution of hyperglycemia or ketoacidosis, or the number of hypoglycemic events among treatment groups. CONCLUSIONS—Our results indicate that the use of subcutaneous insulin aspart every 1 or 2 h represents a safe and effective alternative to the use of intravenous regular insulin in the management of patients with uncomplicated DKA.
Long-Term Follow-Up of Patients Treated With Paclitaxel/Carboplatin-Based Chemotherapy for Advanced Non–Small-Cell Lung Cancer: Sequential Phase II Trials of the Minnie Pearl Cancer Research Network
Authors: John D. Hainsworth, James R. Gray, Lisa H. Morrissey, Leonard A. Kalman, Jeremy K. Hon, F. Anthony Greco
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To provide long-term follow-up on the survival of patients with advanced non–small-cell lung cancer treated with paclitaxel/carboplatin-based regimens in a multicenter, community-based setting. PATIENTS AND METHODS: Between March 1995 and April 1998, 321 patients with newly diagnosed stage IIIB or IV non–small-cell lung cancer were treated on sequential phase II trials with the following combination regimens: paclitaxel/carboplatin, paclitaxel/carboplatin/gemcitabine, and paclitaxel/carboplatin/vinorelbine. Details of these three regimens and patient populations have been previously reported. Responding and stable patients continued treatment until tumor progression or for a recommended six treatment courses. RESULTS: After a median follow-up of 58 months (minimum follow-up, 40 months), the median survival for the entire group of patients was 8.6 months, with actual 1-, 2-, and 3-year survival rates of 40%, 19%, and 7%, respectively. The actuarial 4-year survival rate for the entire group was 4%. No statistically significant differences in survival were seen among the three regimens. Administration of all three regimens was feasible in a community-based setting; however, myelosuppression and hospitalizations for treatment of neutropenia/fever were more frequent with the three-drug regimens. CONCLUSION: Paclitaxel/carboplatin-based regimens, in addition to prolonging median survival and improving 1-year survival, result in substantial improvements in the 2-year survival of patients with advanced non–small-cell lung cancer when compared retrospectively with supportive care or traditional cisplatin-based regimens. In these sequential phase II trials, we did not demonstrate any advantages of three-drug regimens when compared with paclitaxel/carboplatin. Because few patients remain alive after 4 years with any of these chemotherapy regimens, future treatment improvements will require the introduction of novel agents.
Satisfactory cross cultural equivalence of the Dutch WOMAC in patients with hip osteoarthritis waiting for arthroplasty
Authors: L. D. Roorda, C. A. Jones, M. Waltz, G. J. Lankhorst, L. M. Bouter, J. W. Van Der Eijken, W. J. Willems, I. C. Heyligers, D. C. Voaklander, K. D. Kelly, Maria Suarez-Almazor
Journal: Annals of the Rheumatic Diseases (2003)

<b>Background:</b> Cross cultural validity is of vital importance for international comparisons. <b>Objective:</b> To investigate the validity of international Dutch-English comparisons when using the Dutch translation of the Western Ontario and McMaster Universities osteoarthritis index (WOMAC). <b>Patients and Methods:</b> The dimensionality, reliability, construct validity, and cross cultural equivalence of the Dutch WOMAC in Dutch and Canadian patients waiting for primary total hip arthroplasty was investigated. Unidimensionality and cross cultural equivalence was quantified by principal component and Rasch analysis. Intratest reliability was quantified with Cronbach's α, and test-retest reliability with the intraclass correlation coefficient. Construct validity was quantified by correlating sum scores of the Dutch WOMAC, Arthritis Impact Measurement Scales (Dutch AIMS2), Health Assessment Questionnaire (Dutch HAQ), and Harris Hip Score (Dutch HHS). <b>Results:</b> The WOMAC was completed by 180 Dutch and 244 English speaking Canadian patients. Unidimensionality of the Dutch WOMAC was confirmed by principal component and Rasch analysis (good fit for 20/22 items). The intratest reliability of the Dutch WOMAC for pain and physical functioning was 0.88 and 0.96, whereas the test-retest reliability was 0.77 and 0.92, respectively. Dutch WOMAC pain sum score correlated 0.69 with Dutch HAQ pain, and 0.39 with Dutch HHS pain. Dutch WOMAC physical functioning sum score correlated 0.46 with Dutch AIMS2 mobility, 0.62 with Dutch AIMS2 walking and bending, 0.67 with Dutch HAQ disability, and 0.49 with Dutch HHS function. Differential item functioning (DIF) was shown for 6/22 Dutch items. <b>Conclusions:</b> The Dutch WOMAC permits valid international Dutch-English comparisons after correction for DIF.
Percutaneous Endoscopic Gastrostomy (PEG): Comparison of Push and Pull Methods and Evaluation of Antibiotic Prophylaxis
Authors: W. L. Akkersdijk, J. D. van Bergeijk, T. van Egmond, C. J. J. Mulder, G. P. van Berge Henegouwen, C. van der Werken, K. J. van Erpecum
Journal: Endoscopy (1995)

Background and Study Aims: Infection of the gastrostomy opening after placement of a percutaneous endoscopic gastrostomy (PEG) catheter has been reported to occur quite often, especially when the pull method is used. We therefore compared complications occurring with the pull and push methods, and evaluated the role of antibiotic prophylaxis.
Genetic and Non-genetic Predictors of LINE-1 Methylation in Leukocyte DNA
Authors: Salman M. Tajuddin, André F. S. Amaral, Agustín F. Fernández, Sandra Rodríguez-Rodero, Ramón María Rodríguez, Lee E. Moore, Adonina Tardón, Alfredo Carrato, Montserrat García-Closas, Debra T. Silverman, Brian P. Jackson, Reina García-Closas, Ashley L. Cook, Kenneth P. Cantor, Stephen Chanock, Manolis Kogevinas, Nathaniel Rothman, Francisco X. Real, Mario F. Fraga, Núria Malats
Journal: Environmental Health Perspectives (2013)

Altered DNA methylation has been associated with various diseases.We evaluated the association between levels of methylation in leukocyte DNA at long interspersed nuclear element 1 (LINE-1) and genetic and non-genetic characteristics of 892 control participants from the Spanish Bladder Cancer/EPICURO study.We determined LINE-1 methylation levels by pyrosequencing. Individual data included demographics, smoking status, nutrient intake, toenail concentrations of 12 trace elements, xenobiotic metabolism gene variants, and 515 polymorphisms among 24 genes in the one-carbon metabolism pathway. To assess the association between LINE-1 methylation levels (percentage of methylated cytosines) and potential determinants, we estimated beta coefficients (βs) by robust linear regression.Women had lower levels of LINE-1 methylation than men (β = -0.7, p = 0.02). Persons who smoked blond tobacco showed lower methylation than nonsmokers (β = -0.7, p = 0.03). Arsenic toenail concentration was inversely associated with LINE-1 methylation (β = -3.6, p = 0.003). By contrast, iron (β = 0.002, p = 0.009) and nickel (β = 0.02, p = 0.004) were positively associated with LINE-1 methylation. Single nucleotide polymorphisms (SNPs) in DNMT3A (rs7581217-per allele, β = 0.3, p = 0.002), TCN2 (rs9606756-GG, β = 1.9, p = 0.008; rs4820887-AA, β = 4.0, p = 4.8 × 10-7; rs9621049-TT, β = 4.2, p = 4.7 × 10-9), AS3MT (rs7085104-GG, β = 0.7, p = 0.001), SLC19A1 (rs914238, TC vs. TT: β = 0.5 and CC vs. TT: β = -0.3, global p = 0.0007) and MTHFS (rs1380642, CT vs. CC: β = 0.3 and TT vs. CC; β = -0.8, global p = 0.05) were associated with LINE-1 methylation.We identified several characteristics, environmental factors, and common genetic variants that predicted DNA methylation among study participants.
THE RELATION OF THE VITAMINS TO THE REACTION INDUCED BY COAL TAR IN THE TISSUES OF ANIMALS
Authors: Louis H. Jorstad
Journal: The Journal of Experimental Medicine (1925)

Drops of coal tar introduced into the subcutaneous tissue attract the fibroblasts, endothelial and other cells to them. These cells suffer degenerative changes through this action of the tar and the animal suffers cachectic-like changes and death from large doses of it introduced into the subcutaneous tissue. This action of the coal tar is limited to a short period of time, after which it becomes inert. The cells which have been drawn to it and which have not completely degenerated then slowly recover. Where large numbers of these cells are drawn to the tar they grow and divide after recovering from the initial effects of the tar. Cancer may develop. Where only a few cells are drawn to the tar they lay down intercellular fibrils and a scar eventually develops. Vitamin A fed in more than ample quantities to these animals protects the animals and the cells against the toxic action of the tar and stimulates and prolongs their secondary growth. Vitamin B stimulates the secondary growth of these cells. This action is limited in extent and time. It is followed by an early degeneration and hyalinization of the tissue.
iNKT cell development is orchestrated by different branches of TGF-β signaling
Authors: Jean-Marc Doisne, Laurent Bartholin, Kai-Ping Yan, Céline N. Garcia, Nadia Duarte, Jean-Benoît Le Luduec, David Vincent, Farhan Cyprian, Branka Horvat, Sylvie Martel, Ruth Rimokh, Régine Losson, Kamel Benlagha, Julien C. Marie
Journal: The Journal of Experimental Medicine (2009)

Invariant natural killer T (iNKT) cells constitute a distinct subset of T lymphocytes exhibiting important immune-regulatory functions. Although various steps of their differentiation have been well characterized, the factors controlling their development remain poorly documented. Here, we show that TGF-β controls the differentiation program of iNKT cells. We demonstrate that TGF-β signaling carefully and specifically orchestrates several steps of iNKT cell development. In vivo, this multifaceted role of TGF-β involves the concerted action of different pathways of TGF-β signaling. Whereas the Tif-1γ branch controls lineage expansion, the Smad4 branch maintains the maturation stage that is initially repressed by a Tif-1γ/Smad4-independent branch. Thus, these three different branches of TGF-β signaling function in concert as complementary effectors, allowing TGF-β to fine tune the iNKT cell differentiation program.
Stable occurrence of knee and hip total joint replacement in Central Finland between 1986 and 2003: an indication of improved long-term outcomes of rheumatoid arthritis
Authors: T. Sokka, H. Kautiainen, P. Hannonen
Journal: Annals of the Rheumatic Diseases (2006)

<b>Background:</b> Total joint replacement (TJR) surgery is an important severe long-term outcome of rheumatoid arthritis, but relatively little is known about changes of its incidence in patients with rheumatoid arthritis over the past two decades. <b>Methods:</b> A population-based, retrospective, incidence case review was conducted to analyse the frequency of primary TJR surgery of the knee and hip in all patients, and specifically in patients with rheumatoid arthritis in Central Finland between 1986 and 2003. Patients with TJR surgery of the knee and hip were identified in hospital databases over the 18-year period. Age-standardised incidence rate ratios for the primary TJR of the knee and hip were calculated, stratified to sex and diagnosis, with 1986 as the reference value. <b>Results:</b> In patients without rheumatoid arthritis the age-adjusted incidence rate ratios (with 95% CI) for TJR of the knee increased 9.8-fold from 1986 to 2003 in women and men, and for TJR of the hip 1.8-fold in women and 2-fold in men. By contrast, no meaningful change was seen over this period, in age-adjusted incidence rate ratios for TJR of the knee or hip in patients with rheumatoid arthritis, ranging from 0.7 to 1.2 in 2003 compared with 1986. <b>Conclusion:</b> The prevalence of TJR surgery has increased 2–10-fold in patients without rheumatoid arthritis patients, associated with an ageing population, but has not increased in patients with rheumatoid arthritis between 1986 and 2003. These data are consistent with emerging evidence that long-term outcomes of rheumatoid arthritis have improved substantially, even before the availability of biological agents.
Phosphorylation of connexin-43 at serine 262 promotes a cardiac injury-resistant state
Authors: Wattamon Srisakuldee, Maya M. Jeyaraman, Barbara E. Nickel, Stéphane Tanguy, Zhi-Sheng Jiang, Elissavet Kardami
Journal: Cardiovascular Research (2009)

AimsThe cardioprotective agent fibroblast growth factor 2 (FGF-2) was found previously to promote phosphorylation of connexin-43 (Cx43) at protein kinase C (PKC) sites such as serine (S) 262 at levels above those of non-stimulated hearts. We asked if other PKC-dependent cardioprotective treatments cause a similar effect, and if Cx43 phosphorylation at S262 mediates resistance to injury.
Randomized Phase III Study of Gemcitabine and Vinorelbine Versus Gemcitabine, Vinorelbine, and Cisplatin in the Treatment of Advanced Non-Small-Cell Lung Cancer: From the German and Swiss Lung Cancer Study Group
Authors: E. Laack, N. Dickgreber, T. Müller, A. Knuth, J. Benk, C. Lorenz, F. Gieseler, H. Dürk, W. Engel-Riedel, K. Dalhoff, C. Kortsik, U. Graeven, M. Burk, T. Dierlamm, T. Welte, I. Burkholder, L. Edler, D.K. Hossfeld
Journal: Journal of Clinical Oncology (2004)

Purpose To evaluate whether cisplatin-based chemotherapy (gemcitabine, vinorelbine, and cisplatin [GVP]) prolongs overall survival in comparison to cisplatin-free chemotherapy (gemcitabine and vinorelbine [GV]) as first-line treatment in patients with advanced non-small-cell lung cancer (NSCLC). Patients and Methods Between September 1999 and June 2001, 300 patients with NSCLC stage IIIB with malignant pleural effusion or stage IV disease were randomly assigned to receive GV (gemcitabine 1000 mg/m 2 + vinorelbine 25 mg/m 2 on days 1 and 8 every 3 weeks) or GVP (gemcitabine 1000 mg/m 2 + vinorelbine 25 mg/m 2 on days 1 and 8 + cisplatin 75 mg/m 2 on day 2 every 3 weeks). Primary end point of the study was overall survival. Results Two hundred eighty-seven patients (GV, 143 patients; GVP, 144 patients) were eligible for analysis. At the time of analysis, April 15, 2002, 209 patients (GV, 103 patients; GVP, 106 patients) of 287 patients had died (73%). No statistically significant difference was observed for overall survival (P = .73; median survival, 35.9 versus 32.4 weeks; 1-year survival rate, 33.6% versus 27.5%) as well as for event-free survival (P = .35; median time-to-event, 19.3 versus 22.3 weeks) between GV and GVP. Two hundred fourteen patients were assessable for best response. The overall response rates were 13.0% for GV versus 28.3% for GVP (P = .004; complete responders, 0% versus 3.8%; partial responders, 13.0% versus 24.5%). Hematologic and nonhematologic toxicity was significantly lower in the GV treatment arm compared with GVP. No statistically significant difference in quality of life was observed. Conclusion In this phase III study, the cisplatin-based GVP regimen showed no survival benefit as first-line chemotherapy in advanced NSCLC when compared with the cisplatin-free GV regimen, which was substantially better tolerated.
Serum antibody responses to <i>Clostridium difficile</i> toxin A: predictive and protective?
Authors: C PHILLIPS
Journal: Gut (2001)

BackgroundWe have reported that symptom-free carriers of Clostridium diYcile have a systemic anamnestic immune response to toxin A. The aim of this study was to determine whether an acquired immune response to toxin A, during an episode of C. diYcile diarrhoea, influences risk of recurrence. MethodsWe prospectively studied 63 patients with nosocomial C. diYcile diarrhoea.Serial serum IgA, IgG, and IgM concentrations against C. diYcile toxin A, toxin B, or non-toxin antigens were measured by ELISA.Individuals were followed for 60 days.Findings 19 patients died (30%).Of the 44 who survived, 22 had recurrent C. diYcile diarrhoea.Patients with a single episode of C. diYcile diarrhoea (n=22) had higher concentrations of serum IgM against toxin A on day 3 of their first episode of diarrhoea than those with recurrent diarrhoea (n=22, p=0.004).On day 12, serum IgG values against toxin A were higher in patients who had a single episode of diarrhoea (n=7) than in those who subsequently had recurrent diarrhoea (n=9, p=0.009).The odds ratio for recurrence associated with a low concentration of serum IgG against toxin A, measured 12 days after onset of C. difficile diarrhoea, was 48.0 (95% CI 3.5-663). InterpretationA serum antibody response to toxin A, during an initial episode of C. diYcile diarrhoea, is associated with protection against recurrence.
Hydronephrosis associated with retroperitoneal fibrosis and sclerosing pancreatitis
Authors: Hideaki Hamanou, Shigeyuki Kawa, Yasuhide Ochi, Hiroshi Unno, Nobuhiko Shiba, Masahisa Wajiki, Koh Nakazawa, Hisashi Shimojo, Kendo Kiyosawa
Journal: The Lancet (2002)