tbuckley/cabot-search huggingface dataset:
Characterization of Hemodynamic Events Following Intravascular Infusion of Recombinant Adenovirus Reveals Possible Solutions for Mitigating Cardiovascular Responses
Authors: Todd Machemer, Heidrun Engler, Van Tsai, Seoju Lee, Susan Cannon-Carlson, Marcio Voloch, Thomas Schluep, Sundari Ravindran, Gary Vellekamp, Elena Brin, Douglas Cornell, Suganto Sutjipto, Shu Fen Wen, Mark Horn, Nico Van Rooijen, Dan Maneval, Beth Hutchins, Drake LaFace
Journal: Molecular Therapy (2005)

Intravascular administration of recombinant adenovirus (rAd) in cancer patients has been well tolerated. However, dose-limiting hemodynamic responses associated with suppression of cardiac output have been observed at doses of 7.5 x 10(13) particles. While analysis of hemodynamic responses induced by small-molecule pharmaceuticals is well established, little is known about the cardiovascular effects of rAd. Telemetric cardiovascular (CV) monitoring in mice was utilized to measure hemodynamic events following intravascular rAd administration. Electrocardiogram analysis revealed a block in the SA node 3-4 min postinfusion, resulting in secondary pacemaking initiated at the AV node. This was associated with acute bradycardia, reduced blood pressure, and hypothermia followed by gradual recovery. Adenovirus-primed murine sera with high neutralizing antibody (nAb) titers could inhibit CV responses, whereas human sera with equivalent nAb titers induced by natural infection were, surprisingly, not inhibitory. Interestingly, repeat dosing within 2-4 h of the primary injection resulted in desensitization, resembling tachyphylaxis, for subsequent CV responses. Last, depletion of Kupffer cells prior to rAd infusion precluded induction of CV responses. These inhibitory effects suggest that rAd interactions with certain cells of the reticular endothelial system are associated with induction of CV responses. Significantly, these studies may provide insight into management of acute adverse effects following rAd systemic delivery, enabling a broadening of therapeutic index.
Breast Cancer in Postmenopausal Women After Hormone Therapy
Authors: Rod Baber
Journal: JAMA (2011)

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 Journals 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
The aged epidermal permeability barrier. Structural, functional, and lipid biochemical abnormalities in humans and a senescent murine model.
Authors: R Ghadially, B E Brown, S M Sequeira-Martin, K R Feingold, P M Elias
Journal: Journal of Clinical Investigation (1995)

Aged epidermis displays altered drug permeability, increased susceptibility to irritant contact dermatitis, and often severe xerosis, suggesting compromise of the aged epidermal barrier. To delineate the functional, structural, and lipid biochemical basis of epidermal aging, we compared barrier function in young (20-30 yr) vs aged (> 80 yr) human subjects, and in a murine model. Baseline transepidermal water loss in both aged humans and senescent mice was subnormal. However, the aged barrier was perturbed more readily with either acetone or tape stripping (18 +/- 2 strippings vs 31 +/- 5 strippings in aged vs young human subjects, respectively). Moreover, after either acetone treatment or tape stripping, the barrier recovered more slowly in aged than in young human subjects (50 and 80% recovery at 24 and 72 h, respectively, in young subjects vs 15% recovery at 24 h in aged subjects), followed by a further delay over the next 6 d. Similar differences in barrier recovery were seen in senescent vs young mice. Although the total lipid content was decreased in the stratum corneum of aged mice (approximately 30%), the distribution of ceramides (including ceramide 1), cholesterol, and free fatty acids was unchanged. Moreover, a normal complement of esterified, very long-chain fatty acids was present. Finally, stratum corneum lamellar bilayers displayed normal substructure and dimensions, but were focally decreased in number, with decreased secretion of lamellar body contents. Thus, assessment of barrier function in aged epidermis under basal conditions is misleading, since both barrier integrity and barrier repair are markedly abnormal. These functional changes can be attributed to a global deficiency in all key stratum corneum lipids, resulting in decreased lamellar bilayers in the stratum corneum interstices. This constellation of findings may explain the increased susceptibility of intrinsically aged skin to exogenous and environmental insults.
Effects of Long-Acting Thyroid Stimulator on Thyrotropin Stimulation of Adenyl Cyclase Activity in Thyroid Plasma Membranes
Authors: Kamejiro Yamashita, James B. Field
Journal: Journal of Clinical Investigation (1972)

Both thyroid-stimulating hormone (TSH) and long-acting thyroid stimulator (LATS) stimulated adenyl cyclase activity in plasma membranes obtained from bovine thyroid glands. The stimulation induced by LATS was much less than that obtained with maximal amounts of TSH. LATS inhibited TSH stimulation of adenyl cyclase activity while an equivalent amount of normal human γ-globulin did not influence basal or TSH-stimulated activity. The inhibition by LATS appeared to be noncompetitive and was greatest when the plasma membranes were initially exposed to LATS for 30 min at 0°C before being incubated with TSH for 10 min at 37°C. Inhibition could still be demonstrated when the plasma membranes were incubated for 30 min at 0°C with TSH before the addition of LATS. Prolonging the period of incubation of plasma membranes with LATS from 30 to 60 min did not augment the stimulation of adenyl cyclase or increase the inhibition of the effect of TSH. Papain digests of LATS also increased adenyl cyclase activity of thyroid plasma membrane and inhibited the stimulation induced by TSH. The inhibitory effect of LATS was not completely specific for TSH and thyroid plasma membranes since glucagon stimulation of adenyl cyclase in hepatic plasma membranes was also inhibited, but to a lesser extent. In contrast to the results obtained with thyroid plasma membranes, LATS did not influence basal adenyl cyclase activity in hepatic plasma membranes. Furthermore equivalent amounts of normal human γ-globulin also decreased glucagon stimulation of adenyl cyclase activity in plasma membranes obtained from liver. The present data suggest that LATS stimulation of adenyl cyclase in thyroid plasma membranes might be due to a change in the membrane configuration rather than binding to a specific receptor site. Such modification of the membrane structure could interfere with the binding of TSH to specific receptors or to the subsequent stimulation of adenyl cyclase. However, the results do not exclude the possibility that some component in the preparation other than LATS might be responsible for the inhibition of the stimulation by TSH.
Malignant Glioma
Authors: Jay S. Cooper
Journal: JAMA (1982)

Multimodal treatment of malignant gliomas is routinely used at New York University Medical Center. Overall, our treatment program has resulted in survival rates of 78% at six months, 51% at one year, and 7% at five years for these high-grade brain tumors. However, various subgroups (based on tumor or host factors, or both) fared significantly better or worse than others. Particularly limited survival rates were found in patients who experienced paresis/paralysis or impaired mental function, who had tumors that were markedly anaplastic, who were elderly, or who for a variety of reasons did not receive the multimodal treatment we consider optimal. (<i>JAMA</i>1982;248:62-65)
Effectiveness of Right Heart Catheterization: Time for a Randomized Trial-Reply
Authors: Roger C. Bone
Journal: JAMA (1997)

<h3>In Reply.</h3> —As pointed out in the letter from the SCCM, my purpose in the Editorial was to stimulate the National Heart, Lung, and Blood Institute to sponsor research on the risks and benefits of the PA catheter. I also agree with the American Society of Critical Care Anesthesiologists and the guidelines promulgated by their group.<sup>1</sup>I believe if these guidelines were followed explicitly, the treated subgroup would be one likely to have their outcomes improved. I also congratulate the SCCM in conducting a consensus conference to evaluate utilization and education of physicians and other professionals who use the PA catheter. Unfortunately, the lay media emphasized the possibility of a moratorium rather than our advocacy of a randomized controlled trial. I am an advocate of the PA catheter and have used it extensively. Although I cannot prove it, I think there are subgroups of patients in whom the PA catheter has
Spectinomycin and Penicillin G in the Treatment of Gonorrhea
Authors: Alf H. B. Pedersen
Journal: JAMA (1972)

Patients with uncomplicated gonorrhea received either 2.0 gm or 4.0 gm of spectinomycin hydrochloride or currently recommended doses of penicillin G procaine. Of 172 men reexamined within seven days after treatment of gonococcal urethritis, treatment failure rates were 17% for 2.4 mega units of penicillin G procaine, 0% for 2 gm of spectinomycin hydrochloride, and 3.4% for 4 gm of spectinomycin hydrochloride. Of 143 women, failure rates were 13% for 4.8 mega units of procaine penicillin G, 4.3% for 2 gm of spectinomycin hydrochloride, and 4.7% for 4 gm of spectinomycin hydrochloride. Pretreatment isolates of<i>Neisseria</i><i>gonorrhoeae</i>from patients not cured with penicillin G procaine showed increased resistance to penicillin G (<i>P</i>&lt;.001).<i>Neisseria gonorrhoeae</i>shows significant positive correlation of resistance to penicillin G and spectinomycin (<i>P</i>&lt;.01). However, this may not be clinically important, since neither pretreatment or posttreatment isolates of<i>N gonorrhoeae</i>from spectinomycin treatment failures showed increased resistance to spectinomycin.
Effects of Urea and Creatinine on Human Platelet Aggregation.
Authors: James W. Davis
Journal: Annals of Internal Medicine (1968)

s1 May 1968Effects of Urea and Creatinine on Human Platelet Aggregation.James W. Davis, M.D., F.A.C.P., James R. McField, B.S.James W. Davis, M.D., F.A.C.P.Search for more papers by this author, James R. McField, B.S.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-68-5-1166_4 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptClinicians have long been aware of a bleeding tendency in uremic patients. Recently there have been several reports that the platelets of uremic patients have decreased adhesiveness to glass. We measured platelet aggregation by the decrease in optical density which occurred when platelet-rich citrated plasma was agitated with an aggregating agent. We found decreased adenosine diphosphate-induced platelet aggregation in the platelet-rich plasma of 20 nonuremic men after increasing urea nitrogen concentrations by 100 mg/100 ml (P< 0.01) and 200 mg/100 ml (P< 0.001). Increasing concentrations of creatinine by 10 mg/100 ml and 20 mg/100 ml had no significant effect.... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Kansas City, Missouri, and Kansas City, Kansas PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1968Volume 68, Issue 5Page: 1166-1167KeywordsAdenosineAttentionBlood plasmaCreatinineHemorrhagePlatelet aggregationPlateletsUrea Issue Published: 1 May 1968 PDF DownloadLoading ...
Improving NHS performance: human behaviour and health policy
Authors: C. Ham
Journal: BMJ (1999)

<h3>Background and Objectives.</h3> 2-Chloroprocaine is rapidly metabolized in the blood to yield 2-chloro-para-aminobenzoic acid (an inactive metabolite) and diethylaminoethanol (DEAE). DEAE possesses local anesthetic activity. The only reported assay for DEAE is a colorimetric method. <h3>Methods.</h3> Clinical samples of whole blood and serum were obtained from patients receiving stepped intravenous infusions of 3% 2-chloroprocaine. A high pH-dependent liquid-liquid extraction step with diethyl ether was used to eliminate interfering peaks in high-pressure liquid chromatography (HPLC) analysis. Separation and quantitation were performed using HPLC on a polymeric-reversed phase column with a mobile phase consisting of 10% or 20% acetonitrile (for whole blood or serum analysis, respectively) in 50 mm aqueous sodium phosphate buffer, pH = 11.50. The elution order of DEAE and its analogues was tested to interpret the HPLC separation mechanism. <h3>Results.</h3> Extraction recovery of DEAE from whole blood was 67 ± 13.5%, from serum, 71 ± 12.2%, and from water, 75 ± 2.9%. The high pH value of the mobile phase resulted in sharp, well-resolved peaks with run times of approximately 8 minutes using 20% acetonitrile. The lower limit of detection was 5 ng/mL of DEAE from a 1-mL sample. The elution order of DEAE and its analogues indicated that separation was based on the hydrophobicity of the analytes rather than polar group interactions occurring with silica-based stationary phase. <h3>Conclusions.</h3> A new, simple and rapid HPLC method for extraction and measurement of DEAE in whole blood or serum samples is reported here.
Successful Management of Cobra Bite
Authors: Frederick A. Shannon
Journal: JAMA (1961)

<h3>To the Editor:—</h3> I was perturbed by the sweeping conclusions of J. Fred Mullins and Don Naylor in their article on "Successful Management of Cobra Bite with Cryotherapy" inThe Journal, Nov. 26, 1960. There is a vast difference between snake bite and snake envenomization. About 20% of bites result in no envenomization. The percentage of envenomous bites is considerably lower for cobras. Any treatment will result in a high percentage of success if no envenomization occurs. No such bites should be reported without some system of gradation for the Elapidae similar to that of Wood<i>et al. (Virginia Med Monthly</i><b>82</b>:103-135 [March] 1955) for envenomization of the North American Crotalidae. The authors mentioned the use of a tight tourniquet and ice water, always a potentially dangerous combination. This resulted in subsequent gangrenous slough in the finger, a finding not associated with cobra envenomization. Swelling during and after use
The Risk of Death to Trekkers and Hikers in the Mountains
Authors: Martin Burtscher
Journal: JAMA (1995)

To the Editor.  —A few years ago, Drs Shlim and Houston1reported about the risk of death during trekking in Nepal. They calculated a death rate of 15 per 100 000 trekkers and indicated that trekking was safe. However, no comparisons were made. Avery et al2compiled figures for mountaineers in England and Wales and calculated a death rate of 2.3 per 1 million days of exposure.2This risk was 100 times greater than that of ball games and water sports. Using an estimated average of 14 days of exposure per trekker in Nepal, the risk is 11 deaths per 1 million days of exposure—almost five times greater than that indicated by Avery et al.  Since 1986, nearly all fatalities during mountain sports in Austria have been recorded and analyzed by the Health Section of the Austrian Alpine Club. Based on 7 years of observation (1986 through
Lymphocyte responsiveness to Dermatophagoides farinae extract in mite-sensitive patients: effect of immunotherapy on cellular proliferative response and specific immunoglobulin E antibody (RAST score)
Authors: Michio Hiratani, Kazuhiko Muto, Yoshihiro Oshida, Shigeru Ito, Masharu Kasei
Journal: Journal of Allergy and Clinical Immunology (1981)
Complete Remissions in Metastatic Breast Cancer Treated with Combination Drug Therapy
Authors: Sewa S. Legha, Aman U. Buzdar, Terry L. Smith, Gabriel N. Hortobagyi, Kenneth D. Swenerton, George R. Blumenschein, Edmund A. Gehan, Gerald P. Bodey, Emil J. Freireich
Journal: Annals of Internal Medicine (1979)

One hundred sixteen patients with metastatic breast cancer who achieved complete remission with combination chemotherapy were analyzed to ascertain the factors that affect the duration of complete remission and the patterns of relapse. The median duration of complete remission was 17 months. Disease recurred in 81 patients (70%) at periods ranging from 3 to 44 months after achievement of complete remission. The duration of complete remission was inversely related to the bulk of metastatic tumor. Twenty-three patients treated with combined oophorectomy and chemotherapy experienced the longest remissions (median duration of 33 months); only eight (35%) of them have relapsed. Seventy-six percent of the relapses occurred in previously known sites of tumor involvement; most of the remainder involved the brain. The short duration of complete remissions and tendency to relapse in sites of initial involvement suggest that patients with metastatic breast cancer who achieved complete remission with combination chemotherapy still had substantial residual tumor. Consolidation treatments, using hormonal therapy and non-cross-resistant chemotherapy along with irradiation to initial sites of metastases, should be investigated to ascertain their usefulness in prolonging the remissions.
JAK2V617F-positive polycythemia vera and Philadelphia chromosome-positive chronic myeloid leukemia: one patient with two distinct myeloproliferative disorders
Authors: N Cambier, A Renneville, T Cazaentre, V Soenen, C Cossement, S Giraudier, N Grardel, J-L Laï, C Rose, C Preudhomme
Journal: Leukemia (2008)
Research Findings Point to Advances in Breast Cancer Screening and Treatment
Authors: Tracy Hampton
Journal: JAMA (2007)

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
Pressure-limited ventilation with permissive hypercapnia and minimum PEEP in salinelavaged rabbits allows progressive improvement in oxygenation, but does not avoid ventilator-induced lung injury
Authors: K. G. Hickling, I. G. Town, M. Epton, A. Neill, A. Tie, M. Whitehead, P. Graham, E. Everest, G. A'Court, B. Darlow, K. Laubscher
Journal: Intensive Care Medicine (1996)
Common Genetic Polymorphisms Modify the Effect of Smoking on Absolute Risk of Bladder Cancer
Authors: Montserrat Garcia-Closas, Nathaniel Rothman, Jonine D. Figueroa, Ludmila Prokunina-Olsson, Summer S. Han, Dalsu Baris, Eric J. Jacobs, Nuria Malats, Immaculata De Vivo, Demetrius Albanes, Mark P. Purdue, Sapna Sharma, Yi-Ping Fu, Manolis Kogevinas, Zhaoming Wang, Wei Tang, Adonina Tardón, Consol Serra, Alfredo Carrato, Reina García-Closas, Josep Lloreta, Alison Johnson, Molly Schwenn, Margaret R. Karagas, Alan Schned, Gerald Andriole, Robert Grubb, Amanda Black, Susan M. Gapstur, Michael Thun, William Ryan Diver, Stephanie J. Weinstein, Jarmo Virtamo, David J. Hunter, Neil Caporaso, Maria Teresa Landi, Amy Hutchinson, Laurie Burdett, Kevin B. Jacobs, Meredith Yeager, Joseph F. Fraumeni, Stephen J. Chanock, Debra T. Silverman, Nilanjan Chatterjee
Journal: Cancer Research (2013)

Abstract Bladder cancer results from the combined effects of environmental and genetic factors, smoking being the strongest risk factor. Evaluating absolute risks resulting from the joint effects of smoking and genetic factors is critical to assess the public health relevance of genetic information. Analyses included up to 3,942 cases and 5,680 controls of European background in seven studies. We tested for multiplicative and additive interactions between smoking and 12 susceptibility loci, individually and combined as a polygenic risk score (PRS). Thirty-year absolute risks and risk differences by levels of the PRS were estimated for U.S. males aged 50 years. Six of 12 variants showed significant additive gene–environment interactions, most notably NAT2 (P = 7 × 10−4) and UGT1A6 (P = 8 × 10−4). The 30-year absolute risk of bladder cancer in U.S. males was 6.2% for all current smokers. This risk ranged from 2.9% for current smokers in the lowest quartile of the PRS to 9.9% for current smokers in the upper quartile. Risk difference estimates indicated that 8,200 cases would be prevented if elimination of smoking occurred in 100,000 men in the upper PRS quartile compared with 2,000 cases prevented by a similar effort in the lowest PRS quartile (Padditive = 1 × 10−4). Thus, the potential impact of eliminating smoking on the number of bladder cancer cases prevented is larger for individuals at higher than lower genetic risk. Our findings could have implications for targeted prevention strategies. However, other smoking-related diseases, as well as practical and ethical considerations, need to be considered before any recommendations could be made. Cancer Res; 73(7); 2211–20. ©2012 AACR.
The Concept of Functional Asplenia
Authors: Louis K. Diamond
Journal: New England Journal of Medicine (1969)

Removal of the normal spleen (for example, after trauma or during abdominal operations on adjacent structures) is often followed by the appearance of abnormal red cells in the peripheral blood. In certain hematologic disorders in which the spleen is enlarged and is believed to be hyperactive, splenectomy can result in a strikingly bizarre blood smear, containing many red cells with whole nuclei, with nuclear fragments (Howell—Jolly bodies), with precipitated hemoglobin masses (Heinz bodies)1 and with pitted and distorted membranes. The finding of so many abnormal red-cell forms in the peripheral blood after splenectomy has been related to the loss of . . .