tbuckley/cabot-search huggingface dataset:
Aristotle's Champagne
Authors: B. A. St. Andrews
Journal: JAMA (2000)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Implementation of a Pilot Accountable Care Organization Payment Model and the Use of Discretionary and Nondiscretionary Cardiovascular Care
Authors: Carrie H. Colla, Philip P. Goodney, Valerie A. Lewis, Brahmajee K. Nallamothu, Daniel J. Gottlieb, Ellen Meara
Journal: Circulation (2014)

Accountable care organizations (ACOs) seek to reduce growth in healthcare spending while ensuring high-quality care. We hypothesized that accountable care organization implementation would selectively limit the use of discretionary cardiovascular care (defined as care occurring in the absence of indications such as myocardial infarction or stroke), while maintaining high-quality care, such as nondiscretionary cardiovascular imaging and procedures.The intervention group was composed of fee-for-service Medicare patients (n=819 779) from 10 groups participating in a Medicare pilot accountable care organization, the Physician Group Practice Demonstration (PGPD). Matched controls were patients (n=934 621) from nonparticipating groups in the same regions. We compared use of cardiovascular care before (2002-2004) and after (2005-2009) PGPD implementation, studying both discretionary and nondiscretionary carotid and coronary imaging and procedures. Our main outcome measure was the difference in the proportion of patients treated with imaging and procedures among patients of PGPD practices compared with patients in control practices, before and after PGPD implementation (difference-in-difference). For discretionary imaging, the difference-in-difference between PGPD practices and controls was not statistically significant for discretionary carotid imaging (0.17%; 95% confidence interval, -0.51% to 0.85%; P=0.595) or discretionary coronary imaging (-0.19%; 95% confidence interval, -0.73% to 0.35%; P=0.468). Similarly, the difference-in-difference was also minimal for discretionary carotid revascularization (0.003%; 95% confidence interval, -0.008% to 0.002%; P=0.705) and coronary revascularization (-0.02%; 95% confidence interval, -0.11% to 0.07%; P=0.06). The difference-in-difference associated with PGPD implementation was also essentially 0 for nondiscretionary cardiovascular imaging or procedures.Implementation of a pilot accountable care organization did not limit the use of discretionary or nondiscretionary cardiovascular care in 10 large health systems.
Application of Pharmacokinetically Guided Dose Escalation With Respect to Cell Cycle Phase Specificity
Authors: E. Fuse, S. Kobayashi, M. Inaba, H. Suzuki, Y. Sugiyama
Journal: JNCI Journal of the National Cancer Institute (1994)

In 1986, the concept of pharmacokinetically guided dose escalation (PGDE) was proposed to predict the maximum tolerated dose (MTD) of an antitumor drug in humans from animal data. We have previously shown that antitumor drugs can be classified into two types, depending on their cytotoxic mechanisms: type 1 drugs, which are cell cycle phase-nonspecific agents, i.e., area under the curve for drug concentration in the plasma versus time (AUC)-dependent drugs; and type 2 drugs, which are cell cycle phase-specific agents, i.e., those that are time dependent.The validity of the assumption that the AUC at the dose lethal for 10% of mice administered drug (LD10) is equal to the AUC at MTD for humans, the premise on which PGDE is based, was examined for type 1 and 2 drugs.Findings in the literature, including those of Collins and co-workers, were retrospectively analyzed. The human/mouse ratios for the AUC were compared with each other and with the human/mouse dose ratios, based on milligram per meter square of body surface area, the measurement currently used in clinical trials of antitumor drugs. For six of the type 1 drugs, the human/mouse ratio for the AUC of total drug (AUC) and that of unbound drug (AUCu), which has been considered a determinant of pharmacologic and toxicologic effects, were also compared.There was an excellent correlation between log AUC at LD10 for mice and log AUC at MTD for humans for type 1 drugs (r = .898), but not for type 2 drugs (r = .677). For type 1 drugs, the correlation between mouse AUC at LD10 and human AUC at MTD was better for unbound drug (r = .961) than for total drug (r = .892).PGDE is useful for type 1 drugs; differences in protein binding between species should, however, be considered when using this method.
Venous prostaglandin-like activity in diarrhoeal states.
Authors: D W Harris, C H Swan, P R Smith
Journal: Gut (1978)

Prostaglandin E2-like activity was determined in peripheral venous blood of control subjects and in patients with acute gastroenteritis and active ulcerative colitis, using a bioassay method. No significant diurnal variations of prostaglandin levels were detected in the control group, while significantly raised venous plasma prostaglandin-like activity was detected in acute gastroenteritis and in active ulcerative colitis.
Pioglitazone Decreases Plasma Cholesteryl Ester Transfer Protein Mass, Associated With a Decrease in Hepatic Triglyceride Content, in Patients With Type 2 Diabetes
Authors: Jacqueline T. Jonker, Yanan Wang, Willeke de Haan, Michaela Diamant, Luuk J. Rijzewijk, Rutger W. van der Meer, Hildo J. Lamb, Jouke T. Tamsma, Albert de Roos, Johannes A. Romijn, Patrick C.N. Rensen, Johannes W.A. Smit
Journal: Diabetes Care (2010)

OBJECTIVE Thiazolidinediones reduce hepatic steatosis and increase HDL cholesterol levels. In mice with human-like lipoprotein metabolism (APOE*3-Leiden.CETP transgenic mice), a decrease in hepatic triglyceride content is associated with a decrease in plasma cholesteryl ester transfer protein (CETP) mass and an increase in HDL levels. Therefore, the aim of the present study was to assess the effects of pioglitazone on CETP mass in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS We included 78 men with type 2 diabetes (aged 56.5 ± 0.6 years; HbA1c 7.1 ± 0.1%) who were randomly assigned to treatment with pioglitazone (30 mg/day) or metformin (2000 mg/day) and matching placebo, in addition to glimepiride. At baseline and after 24 weeks of treatment plasma HDL cholesterol levels and CETP mass were measured, and hepatic triglyceride content was assessed by proton magnetic resonance spectroscopy. RESULTS Pioglitazone decreased hepatic triglyceride content (5.9 [interquartile range 2.6–17.4] versus 4.1 [1.9–12.3]%, P &amp;lt; 0.05), decreased plasma CETP mass (2.33 ± 0.10 vs. 2.06 ± 0.10 μg/ml, P &amp;lt; 0.05), and increased plasma HDL cholesterol level (1.22 ± 0.05 vs. 1.34 ± 0.05 mmol/l, P &amp;lt; 0.05). Metformin did not significantly change any of these parameters. CONCLUSIONS A decrease in hepatic triglyceride content by pioglitazone is accompanied by a decrease in plasma CETP mass and associated with an increase in HDL cholesterol levels. These results in patients with type 2 diabetes fully confirm recent findings in mice.
Effect of Second-Phase Duration on the Strength-Duration Relation for Human Transvenous Defibrillation
Authors: Stephen R. Shorofsky, Michael R. Gold
Journal: Circulation (2000)

Background —The mechanism by which biphasic waveforms improve defibrillation efficacy is unclear. In addition, the optimal shape of the biphasic waveforms remains controversial. Animal experiments suggest that prolonging the duration of the second phase longer than the first worsens defibrillation thresholds (DFT). The purpose of this study was to determine the strength-duration relation for the second phase of a biphasic defibrillation waveform in humans. Methods and Results —This was a prospective, randomized study of biphasic DFT in 36 patients; a uniform dual-coil transvenous lead system was used. In each patient, 3 DFTs were determined with the pulse duration for the second phase of the defibrillation waveform varying between 1 and 18 ms. The duration of the first phase was fixed at 6 ms and the capacitance was 150 μF. There was a significant increase in the leading edge voltage at DFT only when the second-phase pulse duration was decreased to 1 ms. There was no increase in DFT voltage even when the second-phase pulse duration was increased from 2 to 18 ms. Similar relations were observed for stored energy, leading edge current, or phase 2 energy. The normalized average current delivered during phase 2 decreased monotonically with increasing phase 2 duration. Conclusions —In humans, the biphasic DFT voltage or energy is increased only when the second phase of the waveform is &lt;2 ms. The DFT voltage is insensitive to increasing the second phase of the defibrillator waveform to as long as 18 ms, or 3 times the duration of the first phase of the waveform.
TGF-β1 Promotes Lymphangiogenesis during Peritoneal Fibrosis
Authors: Hiroshi Kinashi, Yasuhiko Ito, Masashi Mizuno, Yasuhiro Suzuki, Takeshi Terabayashi, Fumiko Nagura, Ryohei Hattori, Yoshihisa Matsukawa, Tomohiro Mizuno, Yukihiro Noda, Hayato Nishimura, Ryosuke Nishio, Shoichi Maruyama, Enyu Imai, Seiichi Matsuo, Yoshifumi Takei
Journal: Journal of the American Society of Nephrology (2013)

Peritoneal fibrosis (PF) causes ultrafiltration failure (UFF) and is a complicating factor in long-term peritoneal dialysis. Lymphatic reabsorption also may contribute to UFF, but little is known about lymphangiogenesis in patients with UFF and peritonitis. We studied the role of the lymphangiogenesis mediator vascular endothelial growth factor-C (VEGF-C) in human dialysate effluents, peritoneal tissues, and peritoneal mesothelial cells (HPMCs). Dialysate VEGF-C concentration correlated positively with the dialysate-to-plasma ratio of creatinine (D/P Cr) and the dialysate TGF-β1 concentration. Peritoneal tissue from patients with UFF expressed higher levels of VEGF-C, lymphatic endothelial hyaluronan receptor-1 (LYVE-1), and podoplanin mRNA and contained more lymphatic vessels than tissue from patients without UFF. Furthermore, mesothelial cell and macrophage expression of VEGF-C increased in the peritoneal membranes of patients with UFF and peritonitis. In cultured mesothelial cells, TGF-β1 upregulated the expression of VEGF-C mRNA and protein, and this upregulation was suppressed by a TGF-β type I receptor (TGFβR-I) inhibitor. TGF-β1–induced upregulation of VEGF-C mRNA expression in cultured HPMCs correlated with the D/P Cr of the patient from whom the HPMCs were derived (P<0.001). Moreover, treatment with a TGFβR-I inhibitor suppressed the enhanced lymphangiogenesis and VEGF-C expression associated with fibrosis in a rat model of PF. These results suggest that lymphangiogenesis associates with fibrosis through the TGF-β–VEGF-C pathway.
Reconstruction of Vascular Structure with Multicellular Components using Cell Transfer Printing Methods
Authors: Yu Bin Lee, Indong Jun, Seongwoo Bak, Young Min Shin, Youn‐Mook Lim, Hansoo Park, Heungsoo Shin
Journal: Advanced Healthcare Materials (2014)

Natural vessel has three types of concentric cell layers that perform their specific functions. Here, the fabrication of vascular structure is reported by transfer printing of three different cell layers using thermosensitive hydrogels. Tetronic-tyramine and RGD peptide are co-crosslinked to prepare cell adhesive and thermosensitive hydrogels. The hydrogel increases its diameter by 1.26 times when the temperature reduces from 37 °C to 4 °C. At optimized seeding density, three types of cells form monolayers on the hydrogel, which is then transferred to the target surface within 3 min. Three monolayers are simultaneously transferred on one substrate with controlled shape and arrangement. The same approach is applied onto nanofiber scaffolds that are cultured for more than 5 d. Every type of monolayer shows proliferation and migration on nanofiber scaffolds, and the formation of robust cell-cell contact is revealed by CD31 staining in endothelial cell layer. A vascular structure with multicellular components is fabricated by transfer of three monolayers on nanofibers that are manually rolled with the diameter and length of the tube being approximately 3 mm and 12 mm, respectively. Collectively, it is concluded that the tissue transfer printing is a useful tool for constructing a vascular structure and mimicking natural structure of different types of tissues.
Association of CXCR4 and CCR7 chemokine receptor expression and lymph node metastasis in human cervical cancer
Authors: J. Kodama, None Hasengaowa, T. Kusumoto, N. Seki, T. Matsuo, Y. Ojima, K. Nakamura, A. Hongo, Y. Hiramatsu
Journal: Annals of Oncology (2006)
Comparison of the epidermal growth factor receptor gene and protein in primary non-small-cell-lung cancer and metastatic sites: implications for treatment with EGFR-inhibitors
Authors: A. Italiano, F. Burel Vandenbos, J. Otto, J. Mouroux, D. Fontaine, P.-Y. Marcy, N. Cardot, A. Thyss, F. Pedeutour
Journal: Annals of Oncology (2006)
Phase II Study of the Safety and Antitumor Activity of the Hypoxia-Activated Prodrug TH-302 in Combination With Doxorubicin in Patients With Advanced Soft Tissue Sarcoma
Authors: Sant P. Chawla, Lee D. Cranmer, Brian A. Van Tine, Damon R. Reed, Scott H. Okuno, James E. Butrynski, Douglas R. Adkins, Andrew E. Hendifar, Stew Kroll, Kristen N. Ganjoo
Journal: Journal of Clinical Oncology (2014)

TH-302, a prodrug of the cytotoxic alkylating agent bromo-isophosphoramide mustard, is preferentially activated in hypoxic conditions. This phase II study investigated TH-302 in combination with doxorubicin, followed by single-agent TH-302 maintenance therapy in patients with first-line advanced soft tissue sarcoma (STS) to assess progression-free survival (PFS), response rate, overall survival, safety, and tolerability.In this open-label phase II study, TH-302 300 mg/m(2) was administered intravenously on days 1 and 8 with doxorubicin 75 mg/m(2) on day 1 of each 21-day cycle. After six cycles, patients with stable and/or responding disease could receive maintenance monotherapy with TH-302.Ninety-one patients initiated TH-302 plus doxorubicin induction treatment. The PFS rate at 6 months (primary efficacy measure) was 58% (95% CI, 46% to 68%). Median PFS was 6.5 months (95% CI, 5.8 to 7.7 months); median overall survival was 21.5 months (95% CI, 16.0 to 26.2 months). Best tumor responses were complete response (n = 2 [2%]) and partial response (n = 30 [34%]). During TH-302 maintenance (n = 48), five patients improved from stable disease to partial response, and one patient improved from partial to complete response. The most common adverse events during induction were fatigue, nausea, and skin and/or mucosal toxicities as well as anemia, thrombocytopenia, and neutropenia. These were less severe and less frequent during maintenance. There was no evidence of TH-302-related hepatic, renal, or cardiac toxicity.PFS, overall survival, and tumor response compared favorably with historical outcomes achieved with other first-line chemotherapies for advanced STS. A phase III study of TH-302 is ongoing (NCT01440088).
Fanca deficiency reduces A/T transitions in somatic hypermutation and alters class switch recombination junctions in mouse B cells
Authors: Thuy Vy Nguyen, Lydia Riou, Saïd Aoufouchi, Filippo Rosselli
Journal: The Journal of Experimental Medicine (2014)

Fanconi anemia is a rare genetic disorder that can lead to bone marrow failure, congenital abnormalities, and increased risk for leukemia and cancer. Cells with loss-of-function mutations in the FANC pathway are characterized by chromosome fragility, altered mutability, and abnormal regulation of the nonhomologous end-joining (NHEJ) pathway. Somatic hypermutation (SHM) and immunoglobulin (Ig) class switch recombination (CSR) enable B cells to produce high-affinity antibodies of various isotypes. Both processes are initiated after the generation of dG:dU mismatches by activation-induced cytidine deaminase. Whereas SHM involves an error-prone repair process that introduces novel point mutations into the Ig gene, the mismatches generated during CSR are processed to create double-stranded breaks (DSBs) in DNA, which are then repaired by the NHEJ pathway. As several lines of evidence suggest a possible role for the FANC pathway in SHM and CSR, we analyzed both processes in B cells derived from Fanca−/− mice. Here we show that Fanca is required for the induction of transition mutations at A/T residues during SHM and that despite globally normal CSR function in splenic B cells, Fanca is required during CSR to stabilize duplexes between pairs of short microhomology regions, thereby impeding short-range recombination downstream of DSB formation.
Meta-analyses of Observational and Genetic Association Studies of Folate Intakes or Levels and Breast Cancer Risk
Authors: Sarah J. Lewis, Roger M. Harbord, Ross Harris, George Davey Smith
Journal: JNCI Journal of the National Cancer Institute (2006)

Background: Evidence from case–control studies suggests that increasing dietary folate intake is associated with a reduced risk of breast cancer. However, large cohort studies have found no such association, and animal studies suggest that folate supplementation may promote tumorigenesis. We conducted a meta-analysis to summarize the available evidence from observational studies on this issue and a meta-analysis of the association between a common polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, a key enzyme in folate metabolism, and breast cancer risk. Methods: We searched Medline and ISI Web of Knowledge databases for relevant studies that were published through May 31, 2006. We used random-effects analysis to calculate odds ratios (ORs) for case–control studies or relative risks (RRs) for cohort studies for a 100-μg/d increase in folate intake. Unadjusted odds ratios were calculated for the studies of MTHFR genotype based on published genotype frequencies. Results: A total of 13 case–control studies and nine cohort studies were included in the meta-analysis of folate intake and breast cancer risk. We found a summary OR of 0.91 (95% confidence interval [CI] = 0.87 to 0.96) from the case–control studies and a summary RR of 0.99 (95% CI = 0.98 to 1.01) from the cohort studies for a 100-μg/d increase in folate intake. We found evidence that the case–control studies may have suffered from substantial publication bias. The case–control and cohort studies may have been subject to measurement error, confounding, and possibly spurious associations arising from subgroup analyses; in addition, the case–control studies were potentially subject to recall bias and publication bias. Seventeen studies were included in the meta-analysis of MTHFR C677T genotype and breast cancer risk. We found no difference in breast cancer risk between MTHFR 677 TT homozygotes and CC homozygotes (OR = 1.05, 95% CI = 0.88 to 1.25), and there was no evidence of an interaction between folate intake and MTHFR genotype on breast cancer risk. Conclusion: A lack of dietary folate intake is not associated with the risk of breast cancer.
Toward Gene Therapy for Cystic Fibrosis Using a Lentivirus Pseudotyped With Sendai Virus Envelopes
Authors: Katsuyuki Mitomo, Uta Griesenbach, Makoto Inoue, Lucinda Somerton, Cuixiang Meng, Eiji Akiba, Toshiaki Tabata, Yasuji Ueda, Gad M Frankel, Raymond Farley, Charanjit Singh, Mario Chan, Felix Munkonge, Andrea Brum, Stefania Xenariou, Sara Escudero-Garcia, Mamoru Hasegawa, Eric WFW Alton
Journal: Molecular Therapy (2010)

Gene therapy for cystic fibrosis (CF) is making encouraging progress into clinical trials. However, further improvements in transduction efficiency are desired. To develop a novel gene transfer vector that is improved and truly effective for CF gene therapy, a simian immunodeficiency virus (SIV) was pseudotyped with envelope proteins from Sendai virus (SeV), which is known to efficiently transduce unconditioned airway epithelial cells from the apical side. This novel vector was evaluated in mice in vivo and in vitro directed toward CF gene therapy. Here, we show that (i) we can produce relevant titers of an SIV vector pseudotyped with SeV envelope proteins for in vivo use, (ii) this vector can transduce the respiratory epithelium of the murine nose in vivo at levels that may be relevant for clinical benefit in CF, (iii) this can be achieved in a single formulation, and without the need for preconditioning, (iv) expression can last for 15 months, (v) readministration is feasible, (vi) the vector can transduce human air–liquid interface (ALI) cultures, and (vii) functional CF transmembrane conductance regulator (CFTR) chloride channels can be generated in vitro. Our data suggest that this lentiviral vector may provide a step change in airway transduction efficiency relevant to a clinical programme of gene therapy for CF. Gene therapy for cystic fibrosis (CF) is making encouraging progress into clinical trials. However, further improvements in transduction efficiency are desired. To develop a novel gene transfer vector that is improved and truly effective for CF gene therapy, a simian immunodeficiency virus (SIV) was pseudotyped with envelope proteins from Sendai virus (SeV), which is known to efficiently transduce unconditioned airway epithelial cells from the apical side. This novel vector was evaluated in mice in vivo and in vitro directed toward CF gene therapy. Here, we show that (i) we can produce relevant titers of an SIV vector pseudotyped with SeV envelope proteins for in vivo use, (ii) this vector can transduce the respiratory epithelium of the murine nose in vivo at levels that may be relevant for clinical benefit in CF, (iii) this can be achieved in a single formulation, and without the need for preconditioning, (iv) expression can last for 15 months, (v) readministration is feasible, (vi) the vector can transduce human air–liquid interface (ALI) cultures, and (vii) functional CF transmembrane conductance regulator (CFTR) chloride channels can be generated in vitro. Our data suggest that this lentiviral vector may provide a step change in airway transduction efficiency relevant to a clinical programme of gene therapy for CF.
General Considerations respecting Fever
Authors: C. H. Jones
Journal: BMJ (1858)

IN the following propositions and remarks, an attempt is made to take a general view of the principal phenomena of the febrile state, regarding their pathology from the point of view so well indicated by Parkes and Virchow.I must suppose the wound is closing, with slight discharge.CASE ii.Gun-shot wound of the Chest; Ball Lodged.W.