tbuckley/cabot-search huggingface dataset:
Noninferiority Trials
Authors: Amy H. Kaji, Roger J. Lewis
Journal: JAMA (2015)

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
Activity of SU11248, a Multitargeted Inhibitor of Vascular Endothelial Growth Factor Receptor and Platelet-Derived Growth Factor Receptor, in Patients With Metastatic Renal Cell Carcinoma
Authors: Robert J. Motzer, M. Dror Michaelson, Bruce G. Redman, Gary R. Hudes, George Wilding, Robert A. Figlin, Michelle S. Ginsberg, Sindy T. Kim, Charles M. Baum, Samuel E. DePrimo, Jim Z. Li, Carlo L. Bello, Charles P. Theuer, Daniel J. George, Brian I. Rini
Journal: Journal of Clinical Oncology (2005)

Renal cell carcinoma (RCC) is characterized by loss of von Hippel Lindau tumor suppressor gene activity, resulting in high expression of pro-angiogenic growth factors: vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF). SU11248 (sunitinib malate), a small molecule inhibitor with high binding affinity for VEGF and PDGF receptors, was tested for clinical activity in patients with metastatic RCC.Patients with metastatic RCC and progression on first-line cytokine therapy were enrolled onto a multicenter phase II trial. SU11248 monotherapy was administered in repeated 6-week cycles of daily oral therapy for 4 weeks, followed by 2 weeks off. Overall response rate was the primary end point, and time to progression and safety were secondary end points. Results Twenty-five (40%) of 63 patients treated with SU11248 achieved partial responses; 17 additional patients (27%) demonstrated stable disease lasting > or = 3 months. Median time to progression in the 63 patients was 8.7 months. Dosing was generally tolerated with manageable toxicities.SU11248, a multitargeted receptor tyrosine kinase inhibitor of VEGF and PDGF receptors, demonstrates antitumor activity in metastatic RCC as second-line therapy, a setting where no effective systemic therapy is presently recognized. The genetics of RCC and these promising clinical results support the hypothesis that VEGF and PDGF receptor-mediated signaling is an effective therapeutic target in RCC.
Heterogeneity of the action potential in isolated rat ventricular myocytes and tissue.
Authors: T Watanabe, L M Delbridge, J O Bustamante, T F McDonald
Journal: Circulation Research (1983)

The objectives of this study were to measure action potential parameters in enzyme-dissociated, adult rat ventricular myocytes stimulated at 1 Hz, to compare these measurements with those obtained from intact ventricular tissue, and to determine myocyte and tissue responses at stimulus frequencies between 0.1 and 5 Hz. Action potentials were characterized in terms of amplitude, overshoot, resting potential, duration at 25% and 75% repolarization (APD25, APD75), and Vmax. Based on statistical differences in APD25 and APD75, myocyte action potentials were classified as type I (3.1 +/- 1.0 and 21.5 +/- 3.6 msec), type II (7.4 +/- 1.1 and 38.2 +/- 6.7 msec), or type III (14.5 +/- 1.9 and 46.0 +/- 4.1 msec). Action potentials corresponding to type I were found in right ventricular endocardium and right papillary muscles, and those corresponding to types II and III in the left ventricular endocardium [apex, middle (II); base (III)] and left papillary muscles (II). Myocytes and papillary muscles responded to increases in driving rate with nearly identical lengthening of APD25 and shortening of APD75. The one exception was at 5 Hz where a lengthening of the APD75 occurred in some myocytes. We conclude that action potential configuration in rat ventricle is heterogeneous, and that this is reflected by the different types of action potentials in isolated myocytes. It is likely that the magnitude of a transient outward current is a determinant of action potential configuration, and that slow reactivation of this current is a significant factor underlying the stimulus frequency response.
Increased respiratory burst and phosphodiesterase activity in alveolar eosinophils in chronic eosinophilic pneumonia
Authors: R Aloui, F Gormand, AF Prigent, M Perrin-Fayolle, Y Pacheco
Journal: European Respiratory Journal (1996)

A 43 year old woman presented with chronic eosinophilic pneumonia characterised by a high alveolar eosinophilic count, which allowed biochemical study of these cells. Alveolar eosinophils spontaneously produced high amounts of oxygen free radicals and exhibited an increased level of cyclic adenosine monophosphate (cAMP) phosphodiesterase (PDE) activity compared to blood eosinophils from control or allergic subjects. This activity was preferentially located in the plasma membrane, whilst the PDE activity of blood eosinophils from asthmatics or controls predominated in the cytosol. Because of the potential role of phosphodiesterase during eosinophil activation and recruitment, phosphodiesterase inhibitors may be useful in the treatment of eosinophilic pneumonia.
Serum concentration of 19 serum proteins in Crohn's disease and ulcerative colitis
Authors: B. Weeke, S. Jarnum
Journal: Gut (1971)

The serum concentration of 19 serum proteins was determined by electrophoresis in 42 patients with Crohn9s disease and 36 patients with ulcerative colitis. The results were compared with 78 healthy persons as matched controls. Distinctive, but similar, changes were present in the two diseases. An increased serum concentration of orosomucoid, α<sub>1</sub>-antitrypsin, easily precipitable glycoprotein, α<sub>1</sub>-antichymotrypsin, haptoglobin, and haemopexin was present. The serum concentration was decreased for prealbumin, albumin, α<sub>2</sub>-HS glycoprotein, caeruloplasmin, α<sub>2</sub>-macro-globulin, and transferrin. No significant difference between the two diseases existed as far as the serum protein pattern was concerned. Certain proteins, `the acute phase reactants9 (orosomucoid, α<sub>1</sub>-antitrypsin, α<sub>1</sub>-antichymotrypsin, and haptoglobin) and the immunoglobulins were clinically useful, since their serum concentration reflected the grade of activity of the disease. A pronounced elevation of haptoglobin compared with that of the other `acute phase reactants9 was present in patients with Crohn9s disease complicated by suppurative fistulas or abscesses. Patients with active Crohn9s disease who responded favourably to medical treatment had significantly higher immunoglobulin levels than patients not responding. A similar observation, though not statistically significant, was made in patients with ulcerative colitis.
Laser therapy in 100 tracheobronchial tumours.
Authors: M R Hetzel, C Nixon, W M Edmondstone, D M Mitchell, F J Millard, E M Nanson, A A Woodcock, C E Bridges, A M Humberstone
Journal: Thorax (1985)

One hundred patients with tracheobronchial tumours were treated with the neodymium YAG (yttrium-aluminium-garnet) or argon laser for symptoms of airways obstruction caused by tumour (59 cases), complete collapse of a lung (17 cases), or recurrent haemoptysis (24 cases). Seventy four of them had relapsed or failed to respond to radiotherapy or chemotherapy and all were inoperable. Objective improvement in results of lung function tests or haemoptysis diary charts was seen in 37 patients with airways obstruction (63%), five (29%) with collapsed lung, and 14 (58%) with haemoptysis. Overall, 68 patients had symptomatic benefit and there was objective improvement in 56. Two deaths occurred in 288 treatment sessions both occurring as a result of asphyxia from minor haemorrhage in patients with advanced cylindromas and critical narrowing of the trachea or single remaining bronchus. In suitable patients with intraluminal tumour laser phototherapy is a valuable addition to conventional treatment.
Marathon related cardiac arrest risk differences in men and women
Authors: William O Roberts, Dana M Roberts, Scott Lunos
Journal: British Journal of Sports Medicine (2012)

To determine the incidence of sudden cardiac arrest (SCA) and sudden cardiac death (SCD) in men and women.Retrospective cohort study.Two popular urban 42 km marathons.1982 to 2009 finishers.Race records were assessed for finishers, age distribution and cardiac events by sex.The SCA/SCD incidence for all (total), male and female finishers.There were 548,092 finishers with women finishers increasing from 10% to 40% over the first 18 years and remaining near 40% for the last decade. There were 14 SCA events (1 woman, 13 men) with seven successful resuscitations yielding an all finishers SCA rate of 2.6 per 100,000 finishers. The SCA rates (per 100,000) for men and women were 3.4 (95% CI: 1.8 to 5.9) and 0.6 (95% CI: 0.0 to 3.3), respectively (p=0.079). The male SCA rate for the 2000-2009 decade was 4.6 per 100,000 finishers (95% CI: 1.8 to 9.5). Eleven of 13 men were >39 years old. The OR of a man experiencing SCA compared with woman was 5.7.As the number of women participating in these two marathons has increased, the difference between the men's and total SCA and SCD incidence has increased for men, especially >39 years old, from coronary artery disease with men's incidence for SCA of 1 in 22,000 and SCD at 1 in 50,000 finishers over past decade.
Bacillus anthracis lethal toxin induces TNF-α–independent hypoxia-mediated toxicity in mice
Authors: Mahtab Moayeri, Diana Haines, Howard A. Young, Stephen H. Leppla
Journal: Journal of Clinical Investigation (2003)

Bacillus anthracis lethal toxin (LT) is the major virulence factor of anthrax and reproduces most of the laboratory manifestations of the disease in animals. We studied LT toxicity in BALB/cJ and C57BL/6J mice. BALB/cJ mice became terminally ill earlier and with higher frequency than C57BL/6J mice. Timed histopathological analysis identified bone marrow, spleen, and liver as major affected organs in both mouse strains. LT induced extensive hypoxia. Crisis was due to extensive liver necrosis accompanied by pleural edema. There was no evidence of disseminated intravascular coagulation or renal dysfunction. Instead, analyses revealed hepatic dysfunction, hypoalbuminemia, and vascular/oxygenation insufficiency. Of 50 cytokines analyzed, BALB/cJ mice showed rapid but transitory increases in specific factors including KC, MCP-1/JE, IL-6, MIP-2, G-CSF, GM-CSF, eotaxin, FasL, and IL-1β. No changes in TNF-α occurred. The C57BL/6J mice did not mount a similar cytokine response. These factors were not induced in vitro by LT treatment of toxin-sensitive macrophages. The evidence presented shows that LT kills mice through a TNF-α–independent, FasL-independent, noninflammatory mechanism that involves hypoxic tissue injury but does not require macrophage sensitivity to toxin.
Biological function of Presenilin and its role in AD pathogenesis
Authors: Shuting Zhang, Mingming Zhang, Fang Cai, Weihong Song
Journal: Translational Neurodegeneration (2013)

Presenilins (PSs) are the catalytic core of γ-secretase complex. However, the mechanism of FAD-associated PS mutations in AD pathogenesis still remains elusive. Here we review the general biology and mechanism of γ-secretase and focus on the catalytic components - presenilins and their biological functions and contributions to the AD pathogenesis. The functions of presenilins are divided into γ-secretase dependent and γ-secretase independent ones. The γ-secretase dependent functions of presenilins are exemplified by the sequential cleavages in the processing of APP and Notch; the γ-secretase independent functions of presenilins include stabilizing β-catenin in Wnt signaling pathway, regulating calcium homeostasis and their interaction with synaptic transmission.
Avulsion fracture of the anterior superior iliac spine following apophysitis
Authors: H Pointinger, P Munk, G P Poeschl
Journal: British Journal of Sports Medicine (2003)

The case of an avulsion fracture occurring in an 18 year old athlete after repeated running is presented. The fracture involved the tensor fascia lata muscle and the external oblique abdominal muscle. It was treated by open reduction and internal fixation with two screws. The patient returned to full training, including long distance running, only four weeks after the operation.
Randomized Trial of Postoperative Adjuvant Therapy in Stage II and III Rectal Cancer to Define the Optimal Sequence of Chemotherapy and Radiotherapy: A Preliminary Report
Authors: Jung-Hee Lee, Je-Hwan Lee, Jin-Hee Ahn, Hyeseung Bahng, Tae-Won Kim, Yoon-Koo Kang, Kyoo-Hyung Lee, Jin-Cheon Kim, Chang-Sik Yu, Jong-Hoon Kim, Seung-Do Ahn, Woo-Kun Kim, Sang-Hee Kim, Jung-Shin Lee
Journal: Journal of Clinical Oncology (2002)

PURPOSE: We conducted a prospective randomized trial to define the optimal sequence of chemotherapy and radiotherapy of postoperative adjuvant treatment in stage II and III rectal cancer. PATIENTS AND METHODS: Three hundred eight patients were enrolled onto the study. We randomly assigned 155 to arm I (early radiotherapy group) and 153 to arm II (late radiotherapy group). Treatment included eight cycles of chemotherapy at 4-week intervals and pelvic radiotherapy of 45 Gy in 25 fractions. Radiotherapy started on day 1 of the first chemotherapy cycle in arm I and on day 1 of the third chemotherapy cycle in arm II. The chemotherapy regimen consisted of fluorouracil 375 mg/m 2 /d and leucovorin 20 mg/m 2 /d. Chemotherapy was administered for 3 days per cycle in two cycles during the period of radiotherapy and for 5 days per cycle in the remaining six cycles. RESULTS: Twenty patients in arm I and 14 in arm II were not eligible. We included 274 patients in the analysis. With a median follow-up of 37 months for surviving patients, disease-free survival was significantly prolonged in arm I compared with arm II (81% v 70% at 4 years; P = .043). Twenty-three recurrences occurred in arm I and 38 in arm II (P = .047). Overall survival was not significantly different between arms I and II (84% v 82% at 4 years; P = .387). CONCLUSION: Early radiotherapy with concurrent chemotherapy after resection of stage II and III rectal cancer demonstrated a statistically significant advantage for disease-free survival compared with late radiotherapy with chemotherapy.
Characteristics of Invasive and Noninvasive Human Colorectal Adenocarcinoma Cells
Authors: S. Aznavoorian, L. A. Liotta, H. Z. Kupchik
Journal: JNCI Journal of the National Cancer Institute (1990)

Journal Article Characteristics of Invasive and Noninvasive Human Colorectal Adenocarcinoma Cells Get access Sadie Aznavoorian, Sadie Aznavoorian Department of Microbiology, Boston University School of MedicineBoston, Mass. Search for other works by this author on: Oxford Academic PubMed Google Scholar Lance A. Liotta, Lance A. Liotta Laboratory of Pathology, National Cancer InstituteBethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar Herbert Z. Kupchik Herbert Z. Kupchik * Department of Microbiology, Boston University School of MedicineBoston, Mass.Department of Pathology, Boston University School of MedicineBoston, Mass. *Correspondence to : Herbert Z. Kupchik, M.D., Department of Microbiology, Boston University School of Medicine, 80 E. Concord St., Boston, MA 02118. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 18, 19 September 1990, Pages 1485–1492, https://doi.org/10.1093/jnci/82.18.1485 Published: 19 September 1990 Article history Received: 14 February 1990 Revision received: 25 June 1990 Accepted: 28 June 1990 Published: 19 September 1990
Female-to-Male Transmission of AIDS
Authors: B. Frank Polk
Journal: JAMA (1985)

To the Editor.—  Drs Haverkos and Edelman 1 have addressed perhaps the most important unanswered epidemiologic question regarding human T-cell lymphotropic virus type III (HTLV-III) / lymphadenopathy - associated virus (LAV) transmission. The answer to it will determine the ultimate magnitude of the current pandemic of the acquired immunodeficiency syndrome (AIDS). Fortunately for human society, these authors are probably incorrect in suggesting frequent female-to-male transmission of HTLV-III/LAV. No data are currently available to support the contention that this virus is spread sexually from women to men, at least with other than low frequency/efficiency. Reducing sexual promiscuity—heterosexual and homosexual—may be a sensible public health goal, but this should be achieved with appropriate interventions based on valid data. With the exception of pregnancy, we are accustomed to thinking of sexually transmitted conditions as bidirectional. It has been amply documented that infected men can and do transmit HTLV-III/LAV to susceptible women through various sexual practices,
Effectiveness of bevacizumab added to standard chemotherapy in metastatic colorectal cancer: final results for first-line treatment from the ITACa randomized clinical trial
Authors: A. Passardi, O. Nanni, D. Tassinari, D. Turci, L. Cavanna, A. Fontana, S. Ruscelli, C. Mucciarini, V. Lorusso, A. Ragazzini, G.L. Frassineti, D. Amadori
Journal: Annals of Oncology (2015)
Factors Affecting Cytochrome P-450 3A Activity in Cancer Patients
Authors: Sharyn D. Baker, Ron H. N. van Schaik, Laurent P. Rivory, Albert J. ten Tije, Kimberly Dinh, Wilfried J. Graveland, Paul W. Schenk, Kellie A. Charles, Stephen J. Clarke, Michael A. Carducci, William P. McGuire, Fitzroy Dawkins, Hans Gelderblom, Jaap Verweij, Alex Sparreboom
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The purpose is to identify the demographic, physiologic, and inheritable factors that influence CYP3A activity in cancer patients Experimental Design: A total of 134 patients (62 females; age range, 26 to 83 years) underwent the erythromycin breath test as a phenotyping probe of CYP3A. Genomic DNA was screened for six variants of suspected functional relevance in CYP3A4 (CYP3A4*1B, CYP3A4*6, CYP3A4*17, and CYP3A4*18) and CYP3A5 (CYP3A5*3C and CYP3A5*6). Results: CYP3A activity (AUC0–40min) varied up to 14-fold in this population. No variants in the CYP3A4 and CYP3A5 genes were a significant predictor of CYP3A activity (P &amp;gt; 0.2954). CYP3A activity was reduced by ∼50% in patients with concurrent elevations in liver transaminases and alkaline phosphatase or elevated total bilirubin (P &amp;lt; 0.001). In a multivariate analysis, CYP3A activity was not significantly influenced by age, sex, and body size measures (P &amp;gt; 0.05), but liver function combined with the concentration of the acute-phase reactant, α-1 acid glycoprotein, explained ∼18% of overall variation in CYP3A activity (P &amp;lt; 0.001). Conclusions: These data suggest that baseline demographic, physiologic, and chosen genetic polymorphisms have a minor impact on phenotypic CYP3A activity in patients with cancer. Consideration of additional factors, including the inflammation marker C-reactive protein, as well as concomitant use of other drugs, food constituents, and complementary and alternative medicine with inhibitory and inducible effects on CYP3A, is needed to reduce variation in CYP3A and treatment outcome to anticancer therapy.
In vivo activation of macrophage C3 receptors for phagocytosis.
Authors: F M Griffin, P J Mullinax
Journal: The Journal of Experimental Medicine (1985)

We assessed the effects of exposure to immune complexes in vivo on macrophages' Fc receptor function and C3 receptor function. Peritoneal macrophages from mice injected intraperitoneally with immune complexes were markedly impaired in their ability to phagocytize via their Fc receptors but had acquired the ability to phagocytize via their C3 receptors. In vivo activation of macrophages' C3 receptors for phagocytosis required T lymphocytes, because macrophages from athymic mice could not be activated by injection of immune complexes. The requirement for both T lymphocytes and immune complexes for activation of macrophages' C3 receptors in vivo is identical to the requirements for activation of macrophages' C3 receptors in vitro, suggesting that the mechanisms we have identified for activation of these receptors in vitro are the same mechanisms by which the receptors are activated for phagocytosis in vivo. The susceptibility of macrophages' Fc receptors to blockade by immune complexes and the activation of their C3 receptors for phagocytosis in a milieu containing immune complexes suggest that it may be macrophages' C3 receptors, not their Fc receptors, that are primarily responsible for promoting phagocytosis of opsonized microorganisms in immune hosts.
Risk Factors and Individual Probabilities of Melanoma for Whites
Authors: Eunyoung Cho, Bernard A. Rosner, Diane Feskanich, Graham A. Colditz
Journal: Journal of Clinical Oncology (2005)

Incidence and mortality of cutaneous melanoma is rising rapidly in the United States; therefore, identifying risk factors for melanoma and integrating them into a clinical and population risk estimation tool may help guide prevention efforts and identify participants for preventive interventions.We examined risk factors for melanoma in three large prospective studies of women and men. We observed 152,949 women and 25,206 men free of cancer at baseline for up to 14 years.A total of 535 incident cases of invasive melanoma (444 women and 91 men) were included in the analysis. We combined the three studies to examine risk factors and to build a risk model to calculate melanoma risk score. Older age, male sex, family history of melanoma, higher number of nevi, history of severe sunburn, and light hair color were each associated with significantly elevated risk of melanoma and were included in the final risk prediction. Participants at the highest decile of risk had a more than three-fold increase in risk of melanoma compared with those in the lowest decile (observed relative risk, 3.61; expected relative risk, 4.20). The measure of discriminatory accuracy as summarized by an age-and sex-adjusted concordance statistic of 0.62 (95% CI, 0.58 to 0.65) indicated that the model had reasonable ability to differentiate those who will develop melanoma and those who will remain free from the disease.We identified several risk factors for melanoma and developed statistical models with adequate performance and discriminatory accuracy.