tbuckley/cabot-search huggingface dataset:
Assessment of Patients’ and Physicians’ Compliance to an ACE Inhibitor Treatment Based on Urinary <i>N</i>-Acetyl Ser-Asp-Lys-Pro Determination in the Noninsulin-Dependent Diabetes, Hypertension, Microalbuminuria, Proteinuria, Cardiovascular Events, and Ramipril (DIABHYCAR) Study
Authors: Michel Azizi, Joël Ménard, Séverine Peyrard, Michel Lièvre, Michel Marre, Gilles Chatellier
Journal: Diabetes Care (2006)

The purpose of this study was to assess patients' and physicians' compliance with ACE inhibitor treatment, by measuring an endogenous biomarker of ACE inhibition, urinary N-acetyl-Ser-Asp-Lys-Pro (AcSDKP), in the Noninsulin-Dependent Diabetes, Hypertension, Microalbuminuria, Proteinuria, Cardiovascular Events, and Ramipril (DIABHYCAR) trial, which compared ramipril (1.25 mg o.d.) with placebo in 4,912 patients with type 2 diabetes and microalbuminuria/proteinuria.The urine AcSDKP-to-creatinine ratio was measured blind to treatment in all participants who completed follow-up and provided spot urine samples (n = 1,871).The median urinary AcSDKP-to-creatinine ratio was six times higher for ramipril than for placebo. Urinary AcSDKP-to-creatinine ratios displayed a bimodal distribution in both groups, with a very large intergroup overlap. Based on cluster analysis, we defined truly adherent ramipril patients as those with a ratio > or =4 nmol/mmol and truly adherent placebo patients as those with a ratio < 4 nmol/mmol. After excluding patients withdrawing prematurely from the study or known to have used a nonstudy ACE inhibitor, 27.3% of the 597 ramipril patients had ratios <4, indicating poor compliance, and 9.7% of the 621 placebo patients had ratios > or =4, indicating intake of a nonstudy ACE inhibitor. Correcting for compliance by using AcSDKP-guided analysis affected surrogate outcome results (decrease in systolic blood pressure and urinary albumin excretion) only slightly.The systematic use of spot urinary AcSDKP determination facilitated the detection of defects in compliance with ACE inhibitor treatment in both patients and physicians. Urinary AcSDKP measurement could be a useful biomarker for assessing compliance with ACE inhibition in the routine care of diabetic patients.
Paclitaxel and Carboplatin in the Treatment of Small-Cell Lung Cancer Patients Resistant to Cyclophosphamide, Doxorubicin, and Etoposide: A Non–Cross-Resistant Schedule
Authors: Harry J.M. Groen, Eelco Fokkema, Bonne Biesma, Bibi Kwa, John W.G. van Putten, Pieter E. Postmus, Egbert F. Smit
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To evaluate the efficacy of paclitaxel and carboplatin (PC) in small-cell lung cancer (SCLC) patients resistant to cyclophosphamide, doxorubicin, and etoposide (CDE). PATIENTS AND METHODS: We performed a phase II study with PC in SCLC patients who relapsed within 3 months after first-line treatment with CDE. Paclitaxel administration (175 mg/m 2 by a 3-hour intravenous infusion) was followed by a 30-minute infusion of carboplatin (area under the curve 7; Chatelut formula) once every 3 weeks for five cycles. Dexamethasone, clemastine, and ranitidine were standard premedication before every cycle. RESULTS: Included were 35 patients (median age, 59 years; 16 with limited disease and 19 with extensive disease; Eastern Cooperative Oncology Group performance status of ≤ 1; median time off treatment 6 weeks) who were previously treated with CDE (n = 33), oral etoposide (n = 2), and reinduction CDE (n = 15); only one patient had received three CDE treatments of five cycles. The CDE regimen was followed by local thoracic radiotherapy in seven patients. Hematologic toxicity of grade 3 or 4, for leukopenia was 27% and 6%, for thrombocytopenia 21% and 13%, and for anemia 17% and 0%, respectively, for a total of 132 cycles. Two patients had neutropenic fever; no toxic death occurred. Nonhematologic toxicity was paresthesia CTC grade 3, diarrhea grade 4, and myalgia grade 3 in one patient each. Reversible paresthesia (CTC grade 1 and 2) in toes and fingers was reported in 69% of patients. Thirty-four patients were assessable for response: complete response in two patients, partial response in 23 patients, stable disease in eight patients, and progressive disease in one patient (response rate, 73.5%; 95% confidence interval, 59% to 88%). One patient was found to have atypical carcinoid at pathologic review and was excluded. Median time to progression was 21 weeks (range, 3 to 40 weeks). Median survival was 31 weeks (range, 6 to 112 weeks). One-year survival was 9%. CONCLUSION: Second-line PC in CDE-resistant SCLC patients yields a high response rate and seems non–cross-resistant to CDE. Toxicity was mild in these poor-prognosis patients.
Expression of Cyclin-Dependent Kinase Inhibitors in Vascular Disease
Authors: Felix C. Tanner, Zhi-Yong Yang, Eric Duckers, David Gordon, Gary J. Nabel, Elizabeth G. Nabel
Journal: Circulation Research (1998)

Abstract —Arterial lesions in cardiovascular diseases are characterized by proliferation and migration of smooth muscle cells as well as deposition of connective tissue matrix. Factors that stimulate vascular smooth muscle cell (VSMC) proliferation are well described; however, the role of proteins that limit intimal hyperplasia is not well understood. To examine the function of Kip/Cip and INK cyclin-dependent kinase inhibitors (CKIs) in vascular diseases, the expression of p27 Kip1 and p16 INK was examined in VSMCs in vitro and in porcine arteries and human atherosclerosis in vivo. Western blot and fluorescence activated cell-sorting analysis demonstrated that levels of p27 Kip1 , but not p16 INK , increased during serum deprivation of primary VSMC cultures and caused G 1 arrest. p27 Kip1 inhibited Cdk2 activity, suggesting that Kip CKIs promote G 1 arrest in VSMCs by binding cyclin E/Cdk2. In porcine arteries, p27 Kip1 , but not p16 INK , was constitutively expressed at low levels. Immediately after balloon injury, cell proliferation increased as p27 Kip1 levels declined. Three weeks after injury, p27 Kip1 was strongly expressed in intimal VSMCs when VSMC proliferation was &lt;2%, suggesting that p27 Kip1 functions as an inhibitor of cell proliferation in injured arteries. In contrast, p16 INK expression was detected only transiently early after injury. CKI expression was examined in 35 human coronary arteries, ranging from normal to advanced atherosclerosis. p27 Kip1 expression was abundant in nonproliferating VSMCs and macrophages within normal (7 of 8) and atherosclerotic (25 of 27) arteries. p21 Cip1 levels were undetectable in normal arteries but were elevated in atherosclerotic (19 of 27) arteries. p16 INK could not be detected in normal or atherosclerotic arteries (0 of 35). Thus, the Kip/Cip and INK CKIs have different temporal patterns of expression in VSMCs in vitro and in injured arteries and atherosclerotic lesions in vivo. In contrast to p16 INK , p27 Kip1 likely contributes to the remodeling process in vascular diseases by the arrest of VSMCs in the G 1 phase of the cell cycle.
HEMATOPORPHYRIN AS A THERAPEUTIC AGENT IN THE PSYCHOSES
Authors: Edward A. Strecker, Harold P. Palmer, Francis J. Braceland
Journal: American Journal of Psychiatry (1934)

(1) Hematoporphyrin has a marked photosensitizing power when injected into the human body. The synthetic product, hematoporphyrin hydrochloride (" Photodyn ") has been demonstrated to possess greater photosensitizing power than the compound endogenously produced through disease. (2) Experimentally the drug has been shown to produce alteration in the blood electrolyte values—chiefly calcium. The only one of our patients in whom blood calcium studies were made showed a definite fall in blood calcium during and after hematoporphyrin therapy. (3) Results of animal experimentation seem to show that increased physiologic and psychologic drive results from enteral and parenteral administration of synthetic hematoporphyrin. (4) Hematoporphyrin as a therapeutic agent in the depressive psychoses is reported in foreign literature to be successful in a large majority of cases. So far as we know, no carefully controlled study has yet been done in any substantial number of cases. (5) Thirty-seven patients were studied in our series to determine their responses to hematoporphyrin administration. Twenty-three patients with manic-depressive reactions were treated during the depressed phase with intramuscular and oral administration of hematoporphyrin hydrochloride for an average period of 50 to 6o days. Of this number five showed marked sustained improvement, six showed moderate sustained improvement, and six were generally benefited but the course of the psychosis did not seem to be positively affected. Six gave no favorable response. Seventeen patients of 23 can be said to have been definitely helped by the treatment. (6) Four of eight patients suffering from involutional melancholia showed marked improvement which has been maintained after the treatment was terminated. One was moderately improved and has maintained this gain. Two were generally better during and after treatment but have not made complete recoveries. Only one failed to respond favorably. (7) One schizophrenic of six treated made substantial physical gains, remains generally better and has adjusted his life at a considerably lower level but is working steadily. Definite stimulation ınd animation were evident in all of the schizophrenics treated but in five of these patients the reaction was not of constructive nature. These five subsided into passive states after the treatment was discontinued. (8) It is evident from our experience with hematoporphyrin that when administered to psychotic patients the substance in some way increases the available energy of the individual. The explanation of the mechanism of improvement will have to await more detailed studies. It is significant, however, whatever the physiologic action, that actual somatic and psychic benefits seem to be derived from its administration.
Use in routine clinical practice of two commercial blood tests for diagnosis of infection with Mycobacterium tuberculosis: a prospective study
Authors: Giovanni Ferrara, Monica Losi, Roberto D'Amico, Pietro Roversi, Roberto Piro, Marisa Meacci, Barbara Meccugni, Ilaria Marchetti Dori, Alessandro Andreani, Barbara Maria Bergamini, Cristina Mussini, Fabio Rumpianesi, Leonardo M Fabbri, Luca Richeldi
Journal: The Lancet (2006)
Cytokine regulation of human lung fibroblast hyaluronan (hyaluronic acid) production. Evidence for cytokine-regulated hyaluronan (hyaluronic acid) degradation and human lung fibroblast-derived hyaluronidase.
Authors: P M Sampson, C L Rochester, B Freundlich, J A Elias
Journal: Journal of Clinical Investigation (1992)

We characterized the mechanisms by which recombinant (r) tumor necrosis factor (TNF), IFN-gamma, and IL-1, alone and in combination, regulate human lung fibroblast hyaluronic acid (HA) production. Each cytokine stimulated fibroblast HA production. The combination of rTNF and rIFN-gamma resulted in a synergistic increase in the production of high molecular weight HA. This was due to a synergistic increase in hyaluronate synthetase activity and a simultaneous decrease in HA degradation. In contrast, when rTNF and rIL-1 were combined, an additive increase in low molecular weight HA was noted. This was due to a synergistic increase in hyaluronate synthetase activity and a simultaneous increase in HA degradation. Human lung fibroblasts contained a hyaluronidase that, at pH 3.7, depolymerized high molecular weight HA to 10-40 kD end products of digestion. However, hyaluronidase activity did not correlate with fibroblast HA degradation. Instead, HA degradation correlated with fibroblast-HA binding, which was increased by rIL-1 plus rTNF and decreased by rIFN-gamma plus rTNF. Recombinant IL-1 and rTNF weakly stimulated and rIL-1 and rTNF in combination further augmented the levels of CD44 mRNA in lung fibroblasts. In contrast, rIFN-gamma did not significantly alter the levels of CD44 mRNA in unstimulated or rTNF stimulated cells. These studies demonstrate that rIL-1, rTNF, and rIFN-gamma have complex effects on biosynthesis and degradation which alter the quantity and molecular weight of the HA produced by lung fibroblasts. They also show that fibroblast HA degradation is mediated by a previously unrecognized lysosomal-type hyaluronidase whose function may be regulated by altering fibroblast-HA binding. Lastly, they suggest that the CD44 HA receptor may be involved in this process.
Agonist Antibodies to TNFR Molecules That Costimulate T and NK Cells
Authors: Ignacio Melero, Daniel Hirschhorn-Cymerman, Aizea Morales-Kastresana, Miguel F. Sanmamed, Jedd D. Wolchok
Journal: Clinical Cancer Research (2013)

Abstract Therapy for cancer can be achieved by artificially stimulating antitumor T and natural killer (NK) lymphocytes with agonist monoclonal antibodies (mAb). T and NK cells express several members of the TNF receptor (TNFR) family specialized in delivering a costimulatory signal on their surface. Engagement of these receptors is typically associated with proliferation, elevated effector functions, resistance to apoptosis, and differentiation into memory cells. These receptors lack any intrinsic enzymatic activity and their signal transduction relies on associations with TNFR-associated factor (TRAF) adaptor proteins. Stimulation of CD137 (4-1BB), CD134 (OX40), and glucocorticoid-induced TNFR (GITR; CD357) promotes impressive tumor-rejecting immunity in a variety of murine tumor models. The mechanisms of action depend on a complex interplay of CTL, T-helper cells, regulatory T cells, dendritic cells, and vascular endothelium in tumors. Agonist mAbs specific for CD137 have shown signs of objective clinical activity in patients with metastatic melanoma, whereas anti-OX40 and anti-GITR mAbs have entered clinical trials. Preclinical evidence suggests that engaging TNFR members would be particularly active with conventional cancer therapies and additional immunotherapeutic approaches. Indeed, T-cell responses elicited to tumor antigens by means of immunogenic tumor cell death are amplified by these immunostimulatory agonist mAbs. Furthermore, anti-CD137 mAbs have been shown to enhance NK-mediated cytotoxicity elicited by rituximab and trastuzumab. Combinations with other immunomodulatory mAb that block T-cell checkpoint blockade receptors such as CTLA-4 and PD-1 are also promising. Clin Cancer Res; 19(5); 1044–53. ©2013 AACR.
Use of Fibrates in the United States and Canada
Authors: Cynthia A. Jackevicius
Journal: JAMA (2011)

2][3] The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial recently showed that fenofibrate plus statins in patients with type 2 diabetes did not reduce cardiovascular events more than use of statins alone. 4he only other fenofibrate study, Fenofibrate Intervention and Event Lowering in Diabetes (FIELD), also failed to show reduced cardiovascular morbidity and mortality. 5These negative studies raise questions about a medication with more than $1 billion in sales in the United States. 6vidence that fibrates have clinical benefit is mixed, with most studies focusing on lipid effects. 7,8Fibrates primarily reduce levels of triglycerides with only modest effects on levels of low-density and high-density lipoprotein cholesterol. 7,8The main evidence for clinical benefit comes from placebocontrolled trials with the older fibrates such as gemfibrozil (for which some safety concerns were raised primarily when used with cerivastatin) and clofibrate (which is no longer available due to safety concerns). 9-13These trials exert substantial influence in metaanalyses that show that fibrates in aggregate significantly reduce cardiac events but not overall mortality. 7,8The relevance of this older evidence to contemporary practice is uncertain, particularly given that the only trial to assess fibrates in a population taking statins yielded negative results. 4 A subgroup analysis in a post-ACCORD metaanalysis found that fenofibrate use did not reduce coronary events compared with placebo. 8ttle is known about how fibrates are used in practice.Gemfibrozil and fenofibrate are available in the United States and Canada, bezafibrate is only avail-
The Clinical Spectrum of Severe Imported Falciparum Malaria in the Intensive Care Unit
Authors: Fabrice Bruneel, Laurent Hocqueloux, Corinne Alberti, Michel Wolff, Sylvie Chevret, Jean-Pierre Bédos, Rémy Durand, Jacques Le Bras, Bernard Régnier, François Vachon
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Little is known about severe imported malaria in nonendemic industrialized countries. The purpose of this retrospective study was to describe the clinical spectrum of severe imported malaria in adults and to determine factors that were present at admission and were associated with in-intensive care unit mortality. This retrospective study evaluated the 188 patients who were admitted to our intensive care unit in 1988-1999 with severe and/or complicated imported malaria. Among them, 93 had strictly defined severe malaria, and 95 had less severe malaria. The mean age was 38 years, 51% of patients were nonimmune whites, 94% acquired Plasmodium falciparum in sub-Saharan Africa, and 96% had taken inadequate antimalarial chemoprophylaxis. Mortality was 11% (10 patients) in the severe malaria group, whereas no patients died in the less severe malaria group (p = 0.002). In the bivariable analysis, the main factors associated with death in the severe malaria group were the Simplified Acute Physiology Score, shock, acidosis, coma, pulmonary edema (p < 0.001 for each), and coagulation disorders (p = 0.002). Bacterial coinfection is not infrequent and may contribute to death. Severe imported malaria remains a major threat to travelers. In our population, the most relevant World Health Organization major defining criteria were coma, shock, pulmonary edema, and acidosis.
A new rat model of diabetic macrovascular complication
Authors: C BOUVET, W PEETERS, S MOREAU, D DEBLOIS, P MOREAU
Journal: Cardiovascular Research (2006)

Objectives: Age-related medial calcification (elastocalcinosis) of large arteries is accelerated in diabetes and appears mainly in distal arteries. The aim was to devise a rat model of elastocalcinosis in association with diabetes to examine the hypothesis that diabetes accelerates vascular calcification experimentally.
Predictive value of normal sperm morphology: a structured literature review
Authors: K Coetzee
Journal: Human Reproduction Update (1998)

The aim of the study was to conduct a structured review of the literature published on the use of normal sperm morphology, as an indicator of male fertility potential in the in-vitro fertilization (IVF) situation, and to establish the universal predictive value of this semen parameter. Published literature in which normal sperm morphology was used to predict fertilization and pregnancy, during the period 1978-1996, was reviewed. A total of 216 articles were identified by the sourcing methodology, but only 49 provided data that could be tabulated and analysed. Of these, only 18 provided sufficient data for statistical analysis. Fifteen studies used the strict criteria to evaluate sperm morphology, two used World Health Organization (WHO) guidelines and one used both the strict criteria and the WHO guidelines. All the studies (n=10) using the 5 and 14% normal sperm morphology thresholds (strict criteria) produced positive predictive values for IVF success. In the prediction of pregnancy, 82% (9/11) and 75% (6/8) of the studies produced positive predictive values when using the 5% and 14% thresholds respectively. Aggregating the data produced around the 5% normal sperm morphology threshold (strict criteria), the overall fertilization rates were 59.3% (1979/3337; per oocyte) for the ⩽4% group and 77.6% (10345/13327; per oocyte) for the >4% group, and the overall pregnancy rates were 15.2% (60/395; per cycle) and 26.0% (355/1368; per cycle) respectively. The no-transfer rates across the 5% threshold were 24.0% (86/359; per cycle) in the ⩽4% group compared to 7.4% (80/1088; per cycle) in the >4% group. The inclusion of an accurately evaluated normal sperm morphology count as an integral part of the standard semen analysis makes this analysis still the most cost-effective means of evaluating the male factor.
EORTC study of non-Hodgkin's lymphoma: Phase III study comparing CHVmP-VB and ProMACE-MOPP in patients with stage II, III, and IV intermediate- and high-grade lymphoma
Authors: R. Somers, P. Carde, J. Thomas, U. Tirelli, J.J. Keunig, D. Bron, A. Delmer, R. De bock, C. De Wolf-Peeters, M. van Glabbeke, N. Duez
Journal: Annals of Oncology (1994)
Randomized Phase III Study of Panitumumab With Fluorouracil, Leucovorin, and Irinotecan (FOLFIRI) Compared With FOLFIRI Alone As Second-Line Treatment in Patients With Metastatic Colorectal Cancer
Authors: Marc Peeters, Timothy Jay Price, Andrés Cervantes, Alberto F. Sobrero, Michel Ducreux, Yevhen Hotko, Thierry André, Emily Chan, Florian Lordick, Cornelis J.A. Punt, Andrew H. Strickland, Gregory Wilson, Tudor-Eliade Ciuleanu, Laslo Roman, Eric Van Cutsem, Valentina Tzekova, Simon Collins, Kelly S. Oliner, Alan Rong, Jennifer Gansert
Journal: Journal of Clinical Oncology (2010)

Purpose Panitumumab is a fully human anti–epidermal growth factor receptor (EGFR) monoclonal antibody that improves progression-free survival (PFS) in chemotherapy-refractory metastatic colorectal cancer (mCRC). This trial evaluated the efficacy and safety of panitumumab plus fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone after failure of initial treatment for mCRC by tumor KRAS status. Patients and Methods Patients with mCRC, one prior chemotherapy regimen for mCRC, Eastern Cooperative Oncology Group performance status 0 to 2, and available tumor tissue for biomarker testing were randomly assigned 1:1 to panitumumab 6.0 mg/kg plus FOLFIRI versus FOLFIRI every 2 weeks. The coprimary end points of PFS and overall survival (OS) were independently tested and prospectively analyzed by KRAS status. Results From June 2006 to March 2008, 1,186 patients were randomly assigned 1:1 and received treatment. KRAS status was available for 91% of patients: 597 (55%) with wild-type (WT) KRAS tumors, and 486 (45%) with mutant (MT) KRAS tumors. In the WT KRAS subpopulation, when panitumumab was added to chemotherapy, a significant improvement in PFS was observed (hazard ratio [HR] = 0.73; 95% CI, 0.59 to 0.90; P = .004); median PFS was 5.9 months for panitumumab-FOLFIRI versus 3.9 months for FOLFIRI. A nonsignificant trend toward increased OS was observed; median OS was 14.5 months versus 12.5 months, respectively (HR = 0.85, 95% CI, 0.70 to 1.04; P = .12); response rate was improved to 35% versus 10% with the addition of panitumumab. In patients with MT KRAS, there was no difference in efficacy. Adverse event rates were generally comparable across arms with the exception of known toxicities associated with anti-EGFR therapy. Conclusion Panitumumab plus FOLFIRI significantly improved PFS and is well-tolerated as second-line treatment in patients with WT KRAS mCRC.