tbuckley/cabot-search huggingface dataset:
INFECTIOUS MYXOMATOSIS OF RABBITS
Authors: Joseph E. Smadel, S. M. Ward, Thomas M. Rivers
Journal: The Journal of Experimental Medicine (1940)

A second soluble antigen, separable from the virus, occurs in extracts of infected skin and in the serum of rabbits acutely ill with infectious myxomatosis. Like the first antigen (A), the second (B) is heat labile and has certain characteristics of a globulin. The two antigens precipitate in different concentrations of ammonium sulfate and can be separated by this method. Neither of the antigens after being heated at 56 degrees C. precipitates in the presence of specific antibody but each is capable of inhibiting the activity of its antibody.
Angiotensin II stimulates NADH and NADPH oxidase activity in cultured vascular smooth muscle cells.
Authors: K K Griendling, C A Minieri, J D Ollerenshaw, R W Alexander
Journal: Circulation Research (1994)

The signaling pathways involved in the long-term metabolic effects of angiotensin II (Ang II) in vascular smooth muscle cells are incompletely understood but include the generation of molecules likely to affect oxidase activity. We examined the ability of Ang II to stimulate superoxide anion formation and investigated the identity of the oxidases responsible for its production. Treatment of vascular smooth muscle cells with Ang II for 4 to 6 hours caused a 2.7 +/- 0.4-fold increase in intracellular superoxide anion formation as detected by lucigenin assay. This superoxide appeared to result from activation of both the NADPH and NADH oxidases. NADPH oxidase activity increased from 3.23 +/- 0.61 to 11.80 +/- 1.72 nmol O2-/min per milligram protein after 4 hours of Ang II, whereas NADH oxidase activity increased from 16.76 +/- 2.13 to 45.00 +/- 4.57 nmol O2-/min per milligram protein. The NADPH oxidase activity was stimulated by exogenous phosphatidic and arachidonic acids and was partially inhibited by the specific inhibitor diphenylene iodinium. NADH oxidase activity was increased by arachidonic and linoleic acids, was insensitive to exogenous phosphatidic acid, and was inhibited by high concentrations of quinacrine. Both of these oxidases appear to reside in the plasma membrane, on the basis of migration of the activity after cellular fractionation and their apparent insensitivity to the mitochondrial poison KCN. These observations suggest that Ang II specifically activates enzyme systems that promote superoxide generation and raise the possibility that these pathways function as second messengers for long-term responses, such as hypertrophy or hyperplasia.
Extradural haematoma with sinusitis
Authors: N. R T Pashley
Journal: Journal of the Royal Society of Medicine (2002)

The case report by Papadopoulos et al.1 is a description of complicated frontal sinusitis. This occurs when the infection extends beyond the confines of the bony walls of the sinus involved, and is always the result of an obstructed sinus. It is incorrect to believe that ‘prompt drainage of the [resultant] haematoma and a course of antibiotics should lead to complete recovery’, unless a drainage pathway to the nose is established, in this case through the frontal recess and anterior ethmoid sinus. Currently a transnasal endoscopic approach is used for this, but an external frontoethmoid approach is also safe. Without such a drainage pathway, further complications are very likely to arise from sinusitis sometime in the patient's lifetime.
Five futures for academic medicine
Authors: E Malcolm Symonds, Sir Peter Bell, Jangu Banatvala
Journal: BMJ (2005)

EDITOR—Four factors are responsible for the failure of academic medicine. The first is the research assessment exercise, which, surprisingly, is not discussed in the ICRAM scenarios outlined by Clark for the International Campaign to Revitalise Academic Medicine.1 The second is the inhibition of clinical research by the draconian regulations often inflicted by ethics committees. The third is the formidable problems faced by people wishing to work with …
Phase II Study of Area Under the Plasma-Concentration-Versus-Time Curve–Based Carboplatin Plus Standard-Dose Intravenous Etoposide in Elderly Patients With Small-Cell Lung Cancer
Authors: Hiroaki Okamoto, Koshiro Watanabe, Yutaka Nishiwaki, Kiyoshi Mori, Yuzoh Kurita, Izumi Hayashi, Masayuki Masutani, Koichiro Nakata, Satoshi Tsuchiya, Hiroshi Isobe, Nagahiro Saijo
Journal: Journal of Clinical Oncology (1999)

PURPOSE: The target area under the plasma-concentration-versus-time curve (AUC)–based dosing of carboplatin using Calvert's formula is expected to result in more acceptable toxicity and greater efficacy in elderly patients with small-cell lung cancer (SCLC) than the body surface area–based dosing strategy. This phase II study was designed to determine the toxicity and efficacy of carboplatin based on Calvert's formula plus the standard dose of intravenous etoposide for elderly patients with SCLC. PATIENTS AND METHODS: Carboplatin, dosed to a target AUC of 5 × (24-hour creatinine clearance + 25), was given intravenously on day 1 and etoposide 100 mg/m 2 was given intravenously on days 1, 2, and 3. Patients aged ≥ 70 years old with a performance status of 0 to 2 were eligible. RESULTS: Thirty-six patients were enrolled onto the study. The patient characteristics were as follows: median age, 73 years; limited disease (LD), 16 patients; and extensive disease (ED), 20 patients. Grades 3 and 4 leukopenia occurred in 57% and 3% of patients, and grades 3 and 4 thrombocytopenia occurred in 40% and 11% of patients, respectively. There was one treatment-related death due to hemoptysis. Other toxicities were relatively mild. There were two complete responses and 25 partial responses, for a response rate of 75%. The median survival time was 10.8 months (LD, 11.6 months; ED, 10.1 months), and the 1-year survival rate was 47%. CONCLUSION: This carboplatin/etoposide combination chemotherapy is an active and relatively nontoxic regimen in elderly patients with SCLC, which suggests that the combination may be suitable for randomized controlled trials.
Translational profiles of alpha 1-, alpha 2-, and beta-globin messenger ribonucleic acids in human reticulocytes.
Authors: S H Shakin, S A Liebhaber
Journal: Journal of Clinical Investigation (1986)

In human reticulocytes, the critical balancing of alpha- and beta-globin synthesis may be controlled in part by differential translation of the three major adult globin messenger RNAs (mRNAs), alpha 1, alpha 2, and beta. In this study, we determined, as a parameter of translational efficiency, the relative ribosome loading of these three mRNAs. Using oligonucleotide probes specific for the alpha 1- and alpha 2-globin mRNAs, we find that these two mRNAs have identical translational profiles. Their distribution contrasts with that of beta-globin mRNA, which is present on heavier polyribosomes and is less prevalent in pre-80S messenger ribonucleoprotein fractions. The relative distribution of alpha- vs. beta-globin mRNA is consistent with more efficient beta-globin translation. In contrast, the parallel distributions of alpha 1- and alpha 2-globin mRNAs suggests they are translated with equal efficiencies. Considering the relative concentrations of the two alpha-globin mRNAs in normal reticulocytes, this result predicts a dominant role for the alpha 2-globin locus in human alpha-globin expression.
Gene Expression Profiles of Tumor Biology Provide a Novel Approach to Prognosis and May Guide the Selection of Therapeutic Targets in Multiple Myeloma
Authors: Ariel Anguiano, Sascha A. Tuchman, Chaitanya Acharya, Kelly Salter, Cristina Gasparetto, Fenghuang Zhan, Madhav Dhodapkar, Joseph Nevins, Bart Barlogie, John D. Shaughnessy, Anil Potti
Journal: Journal of Clinical Oncology (2009)

Monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) comprise heterogeneous disorders with incompletely understood molecular defects and variable clinical features. We performed gene expression profiling (GEP) with microarray data to better dissect the molecular phenotypes, sensitivity to particular chemotherapeutic agents, and prognoses of these diseases.Using gene expression and clinical data from 877 patients ranging from normal plasma cells (NPC) to relapsed MM (RMM), we applied gene expression signatures reflecting deregulation of oncogenic pathways and tumor microenvironment to highlight molecular changes that occur as NPCs transition to MM, create a high-risk MGUS gene signature, and subgroup International Staging System (ISS) stages into more prognostically accurate clusters of patients. Lastly, we used gene signatures to predict sensitivity to conventional cytotoxic chemotherapies among identified clusters of patients.Myc upregulation and increasing chromosomal instability (CIN) characterized the evolution from NPC to RMM (P < .0001 for both). Studies of MGUS revealed that some samples shared biologic features with RMM, which comprised the basis for a high-risk MGUS signature. Regarding MM, we subclassified ISS stages into clusters based on shared features of tumor biology. These clusters differentiated themselves based on predictions for prognosis and chemotherapy sensitivity (eg, in ISS stage I, one cluster was characterized by increased CIN, cyclophosphamide resistance, and a poor prognosis).GEP provides insight into the molecular defects underlying plasma cell dyscrasias that may explain their clinical heterogeneity. GEP also may also refine current prognostic and therapeutic models for MGUS and MM.
The effect of carbohydrates on ammonium and ketoacid excretion during starvation
Authors: D. G. Sapir, O. E. Owen, J. T. Cheng, R. Ginsberg, G. Boden, W. G. Walker
Journal: Journal of Clinical Investigation (1972)

The metabolic effects of oral ingestion of minute quantities of carbohydrate during prolonged starvation were studied in nine obese subjects. Measurements were made during a control period of total starvation, during the ingestion of 7.5 g carbohydrate daily, and finally during the ingestion of 15.0 g carbohydrate daily. Daily ketoacid excretion fell after carbohydrate ingestion and was significantly correlated (r = 0.62, P < 0.01) with the amount of carbohydrate administered. Despite this fall in ketoacids, the concentration of blood ketoacids, plasma free fatty acids, and serum insulin remained constant throughout the study. Urinary ammonium excretion, closely correlated with ketoacid output (r = 0.95, P < 0.001), also fell significantly after carbohydrate ingestion. No significant changes were present in extracellular or urinary pH. Urea nitrogen excretion did not change when urinary ammonium output fell. These results indicate that: the excretion of ketoacids and ammonium in starving man is exquisitely sensitive to minute amounts of ingested carbohydrate; the change in ketonuria appears to be due to increased renal ketoacid reabsorption after carbohydrate ingestion; and the nitrogen-sparing effect of reducing renal ammonium output in starvation can be dissociated from nitrogen sparing occurring because of changes in urine urea excretion.
Costs and Cost Effectiveness of a Health Care Provider–Directed Intervention to Promote Colorectal Cancer Screening
Authors: Veena Shankaran, Thanh Ha Luu, Narissa Nonzee, Elizabeth Richey, June M. McKoy, Joshua Graff Zivin, Alfred Ashford, Rafael Lantigua, Harold Frucht, Marc Scoppettone, Charles L. Bennett, Sherri Sheinfeld Gorin
Journal: Journal of Clinical Oncology (2009)

Colorectal cancer (CRC) screening remains underutilized in the United States. Prior studies reporting the cost effectiveness of randomized interventions to improve CRC screening have not been replicated in the setting of small physician practices. We recently conducted a randomized trial evaluating an academic detailing intervention in 264 small practices in geographically diverse New York City communities. The objective of this secondary analysis is to assess the cost effectiveness of this intervention.A total of 264 physician offices were randomly assigned to usual care or to a series of visits from trained physician educators. CRC screening rates were measured at baseline and 12 months. The intervention costs were measured and the incremental cost-effectiveness ratio (ICER) was derived. Sensitivity analyses were based on varying cost and effectiveness estimates.Academic detailing was associated with a 7% increase in CRC screening with colonoscopy. The total intervention cost was $147,865, and the ICER was $21,124 per percentage point increase in CRC screening rate. Sensitivity analyses that varied the costs of the intervention and the average medical practice size were associated with ICERs ranging from $13,631 to $36,109 per percentage point increase in CRC screening rates.A comprehensive, multicomponent academic detailing intervention conducted in small practices in metropolitan New York was clinically effective in improving CRC screening rates, but was not cost effective.
Lewis A. Conner Memorial Lecture. Mechanisms leading to myocardial infarction: insights from studies of vascular biology.
Authors: V Fuster
Journal: Circulation (1994)

Myocardial infarction is the most frequent cause of mortality in the United States as well as in most western countries. In this review, the processes leading to myocardial infarction are described based on the most recent studies of vascular biology; in addition, evolving strategies for prevention are outlined. The following was specifically discussed. (1) Five phases of the progression of coronary atherosclerosis (phases 1 to 5) and eight morphologically different lesions (types I, II, III, IV, Va, Vb, Vc, and VI) in the various phases are defined. (2) The present understanding of the pathogenesis of each of the phases of progression and of the various lesion types preceding myocardial infarction is described; particular emphasis is placed on the physical, structural, cellular, and chemical characteristics of the "vulnerable or unstable plaques" prone to disruption (types IV and Va lesions). (3) The fate of plaque disruption (type VI lesion) in the genesis of the various coronary syndromes and especially acute myocardial infarction is defined; particular emphasis is placed on the combination of plaque disruption and a high thrombogenic risk profile--local factors (ie, degree of plaque disruption, exposure of lipid-macrophage-rich plaque, etc) and systemic factors (ie, catecholamines, RAS, fibrinogen, etc)--in the genesis of myocardial infarction. (4) Strategies of regression or stabilization of "vulnerable or unstable plaques" for prevention of myocardial infarction are presented within the context of recent favorable experience with risk factor modification and lipid-modifying angiographic trials, beta-blockade and angiotensin-converting enzyme inhibition, antithrombotic strategies, and the possible role of estrogens. The recent past has been very fruitful in yielding a better understanding of the processes leading to myocardial infarction, and the near future appears very promising in terms of preventing the number 1 killer in the western world.
Digital Medical Tools and Sensors
Authors: Eric J. Topol, Steven R. Steinhubl, Ali Torkamani
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
Sore throats and antibiotics
Authors: C. Del Mar
Journal: BMJ (2000)

General practice p 150 

The liberal use of antibiotics for sore throats is increasingly frowned on.1 There are three reasons why a clinician might use antibiotics for sore throat: to reduce the risk of complications, to shorten (or reduce the severity of) symptoms, and because of factors related to the consultation (perceived patient demand, ways of terminating the consultation, and so on). Nearly 30 years ago Howie showed a huge variation in different general practitioners' use of antibiotics for sore throat.2 Have general practitioners been thirsting for information on which to base their management? The notion that summarising evidence about an area of care will result in a sort of regulation of doctors' management appears to be naive. A Cochrane review summarising the advantages of antibiotics for sore throat has been available for several years.3 But there is nothing to suggest that there is less variation in practice. General …
Anti-invasive and Antimetastatic Activities of Ribosomal Protein S6 Kinase 4 in Breast Cancer Cells
Authors: Archana Thakur, Yuan Sun, Aliccia Bollig, Jack Wu, Hector Biliran, Sanjeev Banerjee, Fazlul H. Sarkar, D. Joshua Liao
Journal: Clinical Cancer Research (2008)

Abstract Purpose: We have previously shown that p90 ribosomal protein S6 kinase 4 (RSK4), an X-linked gene, is highly up-regulated in mammary tumors of MMTV-c-Myc transgenic mice. In this study, we further investigated whether RSK4 inhibits or promotes breast tumor growth and progression. Experimental Design: Stable overexpression or small interfering RNA–mediated knockdown of RSK4 was done in the MDA-MB-231 cell line. Stable clones were tested for cell proliferation, anchorage-independent growth in soft agar, invasive and metastatic ability of these clones in vitro and tumorigenesis, invasive and metastatic ability in vivo in severe combined immunodeficient mice. Results: Here, we show that exogenous expression of RSK4 resulted in decreased cell proliferation and increased accumulation of cells in G0-G1 phase, which paralleled with enhanced expression of tumor suppressor genes: retinoblastoma protein, retinobl astoma-associated 46 kDa protein, and p21 protein. Overexpression of RSK4 resulted in reduced colony formation in soft agar and suppressed invasive and migratory activities of MDA-MB-231 cells both in vitro and in vivo. Importantly, RSK4-overexpressing cells showed up-regulation of claudin-2 and down-regulation of CXCR4, both of these play roles in invasion and chemotaxis. Conclusions: These results indicate that RSK4 expression may limit the oncogenic, invasive, and metastatic potential of breast cancer cells. Anti-invasive and antimetastatic activities of RSK4 may be, in part, due to its regulation of claudin-2. Increased expression of RSK4 in c-Myc-overexpressing cells and a dose-dependent induction of luciferase reporter gene activity suggest that c-Myc may regulate RSK4 expression.
Independent and incremental prognostic value of doppler-derived mitral deceleration time of early filling in both symptomatic and asymptomatic patients with left ventricular dysfunction
Authors: Pantaleo Giannuzzi, Pier L. Temporelli, Enzo Bosimini, Pedro Silva, Alessandro Imparato, Ugo Corrà, Michele Galli, Amerigo Giordano
Journal: Journal of the American College of Cardiology (1996)
Eligibility and Outcomes Reporting Guidelines for Clinical Trials for Patients in the State of a Rising Prostate-Specific Antigen: Recommendations From the Prostate-Specific Antigen Working Group
Authors: Howard I. Scher, Mario Eisenberger, Anthony V. D'Amico, Susan Halabi, Eric J. Small, Michael Morris, Michael W. Kattan, Mack Roach, Philip Kantoff, Kenneth J. Pienta, Michael A. Carducci, David Agus, Susan F. Slovin, Glenn Heller, William Kevin Kelly, Paul H. Lange, Daniel Petrylak, William Berg, Celestra Higano, George Wilding, Judd W. Moul, Alan N. Partin, Christopher Logothetis, Howard R. Soule
Journal: Journal of Clinical Oncology (2004)

To define methodology to show clinical benefit for patients in the state of a rising prostate-specific antigen (PSA).A clinical states framework was used to address the hypothesis that definitive phase III trials could not be conducted in this patient population.The Group focused on men with systemic (nonlocalized) recurrence and a defined risk of developing clinically detectable metastases. Models to define systemic versus local recurrence, and risk of metastatic progression were discussed.Therapies that have shown favorable effects in more advanced clinical states; meaningful biologic surrogates of activity linked with efficacy in other tumor types; and/or effects on a target or pathway known to contribute to prostate cancer progression in this state can be considered for evaluation.An intervention-specific posttherapy PSA-based outcome definition that would justify further testing should be described at the outset. Reporting: Trial reports should include a table showing the number of patients who achieve a specific PSA-based outcome, the number who remain enrolled onto the trial, and the number who came off study at different time points. The term PSA response should be abandoned.The phases of drug development for this state are optimizing dose and schedule, demonstration of a treatment effect, and clinical benefit. To move a drug forward should require a high bar that includes no rise in PSA in a defined proportion of patients for a specified period of time at a minimum. Agents that do not produce this effect can only be tested in combination. The preferred end point of clinical benefit is prostate cancer-specific survival; the time to development of metastatic disease is an alternative.Methodology to show that an intervention alters the natural history of prostate cancer is described. At each stage of development, only agents with sufficient activity should be moved forward.
A 20-year experience of electron microscopy in the diagnosis of primary ciliary dyskinesia
Authors: J. F. Papon, A. Coste, F. Roudot-Thoraval, M. Boucherat, G. Roger, A. Tamalet, A. M. Vojtek, S. Amselem, E. Escudier
Journal: European Respiratory Journal (2009)

Transmission electron microscopy (TEM) analysis of ciliary ultrastructure is classically used for the diagnosis of primary ciliary dyskinesia (PCD). We report our extensive experience of TEM analysis in a large series of patients in order to evaluate its feasibility and results. TEM analysis performed in 1,149 patients with suspected PCD was retrospectively reviewed. Biopsies (1,450) were obtained from nasal (44%) or bronchial (56%) mucosa in children (66.5%) and adults (33.5%). TEM analysis was feasible in 71.4% of patients and showed a main defect suggestive of PCD in 29.9%. TEM was more feasible in adults than in children, regardless of the biopsy site. Main defects suggestive of PCD were found in 76.9% of patients with sinopulmonary symptoms and in only 0.4% of patients with isolated upper and 0.4% with isolated lower respiratory tract infections. The defect pattern was similar in children and adults, involving dynein arms (81.2%) or central complex (CC) (18.8%). Situs inversus was never observed in PCD patients with CC defect. Kartagener syndrome with normal ciliary ultrastructure was not an exceptional condition (10.2% of PCD). In conclusion, TEM analysis is feasible in most patients and is particularly useful for PCD diagnosis in cases of sinopulmonary syndrome of unknown origin.