tbuckley/cabot-search huggingface dataset:
Researchers Seek New Uses for Sildenafil
Authors: Mike Mitka
Journal: JAMA (2003)

CHICAGO—Now that time and experience have established the role of sildenafil nitrate (Viagra) in the treatment of erectile dysfunction (ED), researchers are turning their attention to studying how the drug may improve outcomes for other problems, as well as its safety and efficacy when combined with other therapies. Studies presented here at the Annual Scientific Meeting of the American Urological Association in late April found researchers pondering the use of sildenafil in patients with rapid ejaculation, in men with ED and lower urinary tract symptoms, and those undergoing radical prostatectomies. “With the efficacy and safety issues of sildenafil for erectile dysfunction basically settled, from a scientific point of view, you need to explore new frontiers,” said Harin Padma-Nathan, MD, clinical professor at the Keck School of Medicine of the University of Southern California in Los Angeles. Those new frontiers center around sildenafil’s enhancement of nitric oxide, a signaling molecule that controls a diverse range of physiological processes in many tissues. Scientists believe that nitric oxide regulates vascular tone and promotes blood vessel relaxation, and plays roles in the immune system, nervous system, and in inflammation. When stimulated, nitric oxide activates the enzyme guanylate cyclase. This, in turn, increases levels of cyclic guanosine monophosphate (cGMP), which causes smooth muscle relaxation. In the penis, this allows an inflow of blood leading to erection. Another enzyme, phosphodiesterase type 5 (PDE5) degrades the effectiveness of cGMP and its ability to create smooth muscle relaxation (leading to ED). Sildenafil inhibits PDE5, allowing cGMP to function more effectively.
Still Life With Grapes and Figs
Authors: M. Therese Southgate
Journal: JAMA (2002)

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
7.5% NaCl with adenosine, lidocaine and Mg2+ (ALM) improves hypotensive resuscitation in the pressure-controlled rat model of severe hemorrhagic shock
Authors: Hayley L. Letson, Geoffrey P. Dobson
Journal: Circulation (2010)

Much controversy exists over the fluid composition for hypotensive resuscitation. Previously we showed that a small volume of 7.5% NaCl/6% Dextran-70 (RescueFlow®) or 7.5% NaCl/hydroxyethyl starch (HES) led to cardiac instability and mortality (HES). Our aim was to examine the early resuscitative effects of 7.5% NaCl with adenosine, lidocaine and magnesium (AdenocaineTM) (ALM) on mortality and hemodynamics in the rat model of severe hemorrhagic shock.

Methods: Male fed Sprague-Dawley rats (300–450g, n=48) were anesthetized and randomly assigned to one of six groups: 1) Untreated 2) 7.5% saline, 3) 7.5% NaCl/Mg2+ (M), 4) 7.5% NaCl with adenosine/Mg2+(AM), 5) 7.5% NaCl with lidocaine/Mg2+ (LM), 6) 7.5% NaCl with ALM. Hemorrhagic shock was induced by phlebotomy until MAP was 35–40 mmHg and continued for 20 min (~40% blood loss). Animals were left in shock for 60 min at 34°C. 0.3 ml (~ 3.5% of shed blood) was injected as a 10 sec intravenous (IV) bolus. Lead II ECG, arterial blood pressures, MAP, heart rate and rate-pressure product (RPP) were monitored.

Results: Untreated rats experienced severe arrhythmias and 38% mortality. There were no deaths in any treatment group. 7.5% NaCl alone failed to maintain MAP after 5 min. Interestingly, the presence of Mg2+ had a colloid-like effect, and at 60 min the MAP was 48±2 mmHg vs. 36±5 mmHg for the 7.5% NaCl group (P<0.05). In addition, the Mg2+ group showed a 25% higher RPP than 7.5% NaCl alone. 7.5% NaCl with ALM led to further increases in MAP and was significantly higher than all other treatment groups (MAP was 60 mmHg at 60 min; P<0.05). This higher MAP was associated with a twofold increase in diastolic pressure compared with 7.5% NaCl alone or AM or LM groups. Both 7.5% NaCl with AM or LM were mildly bradycardic but not when combined as ALM. A few arrhythmias occurred in 7.5% NaCl group with or without Mg2+, but no arrhythmias occurred in the other treatment groups.

Conclusions: 7.5% NaCl with ALM led to a significantly higher MAP (P<0.05), higher diastolic rescue, higher RPP and a more electrically stable heart compared with other treatment groups. Ultra-small (<1ml/kg) intravenous bolus of 7.5% NaCl with ALM may have clinical applications in the early treatment of hemorrhagic shock on the battlefield or in out-of-hospital environments.
25-Hydroxycholesterol induces mtDNA damage and loss of mitochondrial function in CEM cells
Authors: Sylvette Ayala-Torres, Yomaira Torres, Betania Pichardo, Nydia Rosario
Journal: Cancer Research (2004)

766  Oxysterols are cholesterol oxidation products that potently induce apoptosis in human lymphoid cells. However, the mechanism(s) by which oxysterols trigger apoptosis in these cells is unknown. The apoptotic effects of oxysterols in leukemic cells have been linked to their participation in the generation of reactive oxygen species (ROS). In addition to nuclear DNA damage, ROS can also cause damage to mitochondrial DNA (mtDNA) and this damage can lead to the loss of mitochondrial function. We hypothesize that oxysterol-induced apoptosis leads to mtDNA damage and loss of mitochondrial function. We applied a quantitative polymerase chain reaction (QPCR) assay to assess the relative amounts of mtDNA damage after oxysterol treatment of the human leukemic cell line CEM. The QPCR assay is based on the principle that oxidative DNA damage such as strand breaks, base modifications and abasic sites block the progression of any thermostable PCR polymerase on the DNA template, resulting in a decrease in amplification of a target DNA sequence. Our data show a dose-dependent increase in the levels of mtDNA damage in the oxysterol-sensitive CEMC7 cells exposed to 25-hydroxycholesterol (25OHC), as shown by a 33% and 46% reduction in the amplification of a 10.0-kb mtDNA fragment when exposed for 48 h to 50 and 300 nM 25OHC, respectively. Our data also show a dose-dependent decrease in ATP levels in the oxysterol-sensitive CEMC7 cells 48 h after exposure to 25OHC (20 and 50% reduction after 300 and 1000 nM 25OHC, respectively). In addition, we show that in the oxysterol-sensitive CEMC7 cells, 25OHC treatment elicits a dose-dependent loss of mitochondrial membrane potential 48 h after 25OHC exposure (25, 45, and 60% reduction after 100, 300, and 1000 nM 25OHC, respectively). These effects were not observed in the oxysterol-resistant M10R5 cells, which do not undergo apoptosis in the presence of 25OHC. These results support our hypothesis that mitochondria are target of oxidative damage during oxysterol-induced apoptosis of human CEM cells and suggest a possible role for mtDNA damage and loss of mitochondrial function in apoptosis. (Supported by a grant from NIH-RCMI 2 G12RR030335-16).
Abstract 3174: Administration of Cyclin A2 by Gene Transfer Improves Cardiac Function in a Porcine Model of Myocardial Infarction
Authors: Scott Shapiro, Yoshiaki Kawase, Dennis Ladage, Gabriela Guzman Martinez, Javier Sanz, Mario J Garcia, Hina W Chaudhry, Roger J Hajjar
Journal: Circulation (2009)
Absence of association between ex vivo susceptibility to doxycycline and pftetQ and pfmdt copy numbers in Plasmodium falciparum isolates from Dakar, Senegal
Authors: T. Gaillard, B. Fall, A. Tall, N. Wurtz, B. Diatta, M. Lavina, K.B. Fall, F.D. Sarr, E. Baret, Y. Diémé, B. Wade, R. Bercion, S. Briolant, B. Pradines
Journal: Clinical Microbiology and Infection (2012)
Mutations in ATP2C1, encoding a calcium pump, cause Hailey-Hailey disease
Authors: Zhilan Hu, Jeannette M. Bonifas, Jenna Beech, Graham Bench, Takako Shigihara, Hideoki Ogawa, Shigaku Ikeda, Theodora Mauro, Ervin H. Epstein
Journal: Nature Genetics (2000)
Beware online therapy, counselling association warns
Authors: Zosia Kmietowicz
Journal: BMJ (2001)

People using the internet to access a therapist are being warned to take precautions to protect themselves against fraudulent practitioners.

Guidelines from the British Association for Counselling and Psychotherapy this month recommend that anyone considering internet counselling should ensure that the therapist is suitably trained and supervised and that they understand the contract they are agreeing to and the limitations of the service they are receiving.

“Online therapy has enormous potential, and this is an exciting new area,” said one of the report's authors, Dr …
Abstract 11482: Combined Algorithm Using a Poor Increase in Inferior P-Wave Amplitude During Sympathetic Stimulation and Conventional CSNRT as a Diagnostic Method for Sick Sinus Syndrome
Authors: Jin kyu Park, Junbeom Park, Hee-Sun Mun, Jae-Sun Uhm, Hui-Nam Pak, Moon-Hyong Lee, Boyoung Joung
Journal: Circulation (2014)

Introduction: Sick sinus syndrome (SSS) is mainly diagnosed based on clinical criteria and there is still no non-invasive study to assess the degree of sinoatrial node (SAN) dysfunction. Hypothesis: This study sought to evaluate whether a combined algorithm using a poor increase in inferior P-wave amplitude during sympathetic stimulation and conventional CSNRT might be a helpful diagnostic tool for SSS. Methods: Three dimensional endocardial mapping of right atrium (RA), P-wave amplitude of inferior axis and corrected sinus node recovery time (CSNRT) were compared in consecutive 105 atrial fibrillation patients with (n=18) and without SSS (n=87). Results: The distances from the superior vena cava (SVC) to the RA early activation site (EAS) were negatively correlated with P-wave amplitude of lead II (r=-0.41, p<0.001), III (r=-0.41, p<0.001) and aVF (r=-0.43, p<0.001). The significant cranial shift of EAS (the distance from SVC to EAS: 11.0 vs. 6.1 mm, p<0.001), and the increase of P-wave amplitude of lead...
The Long Hall
Authors: Floyd Skloot
Journal: JAMA (2002)

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
T Cells Engineered With Chimeric Antigen Receptors Targeting NKG2D Ligands Display Lethal Toxicity in Mice
Authors: Heather VanSeggelen, Joanne A Hammill, Anna Dvorkin-Gheva, Daniela GM Tantalo, Jacek M Kwiecien, Galina F Denisova, Brian Rabinovich, Yonghong Wan, Jonathan L Bramson
Journal: Molecular Therapy (2015)

Ligands for the NKG2D receptor are overexpressed on tumors, making them interesting immunotherapy targets. To assess the tumoricidal properties of T cells directed to attack NKG2D ligands, we engineered murine T cells with two distinct NKG2D-based chimeric antigen receptors (CARs): (i) a fusion between the NKG2D receptor and the CD3ζ chain and (ii) a conventional second-generation CAR, where the extracellular domain of NKG2D was fused to CD28 and CD3ζ. To enhance the CAR surface expression, we also engineered T cells to coexpress DAP10. In vitro functionality and surface expression levels of all three CARs was greater in BALB/c T cells than C57BL/6 T cells, indicating strain-specific differences. Upon adoptive transfer of NKG2D-CAR-T cells into syngeneic animals, we observed significant clinical toxicity resulting in morbidity and mortality. The severity of these toxicities varied between the CAR configurations and paralleled their in vitro NKG2D surface expression. BALB/c mice were more sensitive to these toxicities than C57BL/6 mice, consistent with the higher in vitro functionality of BALB/c T cells. Treatment with cyclophosphamide prior to adoptive transfer exacerbated the toxicity. We conclude that while NKG2D ligands may be useful targets for immunotherapy, the pursuit of NKG2D-based CAR-T cell therapies should be undertaken with caution. Ligands for the NKG2D receptor are overexpressed on tumors, making them interesting immunotherapy targets. To assess the tumoricidal properties of T cells directed to attack NKG2D ligands, we engineered murine T cells with two distinct NKG2D-based chimeric antigen receptors (CARs): (i) a fusion between the NKG2D receptor and the CD3ζ chain and (ii) a conventional second-generation CAR, where the extracellular domain of NKG2D was fused to CD28 and CD3ζ. To enhance the CAR surface expression, we also engineered T cells to coexpress DAP10. In vitro functionality and surface expression levels of all three CARs was greater in BALB/c T cells than C57BL/6 T cells, indicating strain-specific differences. Upon adoptive transfer of NKG2D-CAR-T cells into syngeneic animals, we observed significant clinical toxicity resulting in morbidity and mortality. The severity of these toxicities varied between the CAR configurations and paralleled their in vitro NKG2D surface expression. BALB/c mice were more sensitive to these toxicities than C57BL/6 mice, consistent with the higher in vitro functionality of BALB/c T cells. Treatment with cyclophosphamide prior to adoptive transfer exacerbated the toxicity. We conclude that while NKG2D ligands may be useful targets for immunotherapy, the pursuit of NKG2D-based CAR-T cell therapies should be undertaken with caution.
1 in 4 pregnant women in South Africa has HIV
Authors: Pat Sidley
Journal: BMJ (2001)

The South African government has released its annual figures on HIV and AIDS, which show a continued increase in the numbers of people contracting the virus. About 4.7 million South Africans now have the virus, compared with 4.2m in 1999.

Some 24.5% of pregnant women were infected with HIV, according to a survey of 16 548 blood samples in the year 2000. The equivalent …
Abstract 19005: Staying Connected: a CVD Risk Intervention for Young Black Women
Authors: Jo-Ann Eastwood, Debra K Moser, Nabil Alshurafa, Lynn V Doering, Karol Watson, Majid Sarrafzadeh
Journal: Circulation (2014)

Fifty thousand Black women, disproportionately affected by cardiovascular disease (CVD), die annually; 49% of Black women ≥ 20 years have CVD. Implementing proactive risk reduction is essential. The purpose of this community - based pilot was to test the feasibility of a program combining self-care education with wireless individualized feedback via a unique smartphone designed to appeal specifically to young Black women (YBW). Methods: Using church-based recruitment, 49 YBW (aged 25-45 years, 60% single) were randomized to treatment (TX) and control groups by church site. The TX group participated in 4 interactive self-care classes on CVD risk reduction. Each participant set individualized goals. Risk factor profiles (waist circumference (WC), BP, lipid panel by Cholestech [Alere]), medical and reproductive history and a battery of psychosocial instruments were assessed prior to classes and 6 months later. Participants were given smartphones with embedded accelerometers and WANDA-CVD, an application that delivered prompts and messages specifically for this pilot. For activity monitoring, phones were worn on the hip during waking hours. Participants obtained and transmitted BP measurements wirelessly via the phone. Changes over time were measured with paired t-tests and linear regression controlling for age and weight. Effect sizes were calculated using Cohen’s D. Results: In risk factor profiles, significant differences favoring the TX group occurred in DBP, WC, and TC/HDL ratio; similar changes in triglycerides yielded a medium-large effect size (Table). TX participants had greater drops in stress, anxiety, and better adherence to heart healthy habits. Conclusion: These interim pilot data validate the feasibility of a combined education/wireless monitoring-feedback program in YBW. Further testing in a large randomized trial is warranted to determine long-term effects on behavior change and cardiac risk profiles in this high risk population.
The Chemokine Receptor CXCR-4 Is Expressed on CD34+Hematopoietic Progenitors and Leukemic Cells and Mediates Transendothelial Migration Induced by Stromal Cell-Derived Factor-1
Authors: Robert Möhle, Frank Bautz, Shahin Rafii, Malcolm A.S. Moore, Wolfram Brugger, Lothar Kanz
Journal: Blood (1998)
Abstract 17934: Normal Doppler Hemodynamics of Pulmonary Valve Prostheses in Adults
Authors: Arvind Hoskoppal, Heidi Connolly, Fletcher Miller, Joseph Dearani, Hartzell Schaff, Lori Blauwet
Journal: Circulation (2014)

Introduction: Pulmonary valve (PV) replacement is rare, so data regarding normal hemodynamics are limited. We sought to determine the normal Doppler-derived hemodynamic profiles of various PV prostheses (PVPs) in adults. Hypothesis: Doppler-derived hemodynamic profiles of normal PVPs will vary according to prosthesis type in adult patients. Methods: We performed a retrospective review of comprehensive two dimensional and Doppler echocardiographic examinations of 327 patients (median age, 35; range 18 -83 years) with normal PVPs performed early after implantation. Data were analyzed to determine mean±SD. Results: Parasternal short axis was the most commonly used window (96%) for assessment of PVPs. For the 327 PVPs, peak instantaneous gradient was 25±11 mmHg, mean systolic gradient was 13.1±6.1 mmHg, and mean right ventricular outflow tract velocity was 0.8±0.6 m/s. Results for selected variables analyzed by prosthesis type are listed in the Table. Pericardial prostheses had significantly lower peak gradient (21±10.1 mmHg; P=0.002) compared with porcine (25±9.7 mmHg), mechanical (26±16.6 mmHg), bovine venous (34±15.5 mmHg) and homograft PVPs (35±8.4 mm Hg). Conclusions: This is the largest series reporting normal Doppler-derived hemodynamic profiles of PVPs. This study establishes normative values for Doppler-derived variables for normal PVPs implanted in adults. Pericardial prostheses had the optimal hemodynamic profile in this patient population.
Terlipressin or vasopressin plus transdermal nitroglycerin in a treatment strategy for digestive bleeding in cirrhosis
Authors: Gennaro D'Amico, Mario Traina, Giovanni Vizzini, Fabio Tinè, Flavia Politi, Luigi Montalbano, Angelo Luca, Linda Pasta, Luigi Pagliaro, Alberto Morabito
Journal: Journal of Hepatology (1994)
Combination immunotherapy with α-CTLA-4 and α-PD-L1 antibody blockade prevents immune escape and leads to complete control of metastatic osteosarcoma
Authors: Danielle M Lussier, John L Johnson, Pooja Hingorani, Joseph N Blattman
Journal: Journal for ImmunoTherapy of Cancer (2015)

Osteosarcoma is one of the most common bone cancers in children. Most patients with metastatic osteosarcoma die of pulmonary disease and limited curative therapeutic options exist for such patients. We have previously shown that PD-1 limits the efficacy of CTL to mediate immune control of metastatic osteosarcoma in the K7M2 mouse model of pulmonary metastatic disease and that blockade of PD-1/PD-L1 interactions can partially improve survival outcomes by enhancing the function of osteosarcoma-specific CTL. However, PD-1/PD-L1 blockade-treated mice eventually succumb to disease due to selection of PD-L1 mAb-resistant tumor cells. We investigated the mechanism of tumor cell resistance after blockade, and additional combinational therapies to combat resistance.We used an implantable model of metastatic osteosarcoma, and evaluated survival using a Log-rank test. Cellular analysis of the tumor was done post-mortem with flow cytometry staining, and evaluated using a T-test to compare treatment groups.We show here that T cells infiltrating PD-L1 antibody-resistant tumors upregulate additional inhibitory receptors, notably CTLA-4, which impair their ability to mediate tumor rejection. Based on these results we have tested combination immunotherapy with α-CTLA-4 and α-PD-L1 antibody blockade in the K7M2 mouse model of metastatic osteosarcoma and show that this results in complete control of tumors in a majority of mice as well as immunity to further tumor inoculation.Thus, combinational immunotherapy approaches to block additional inhibitory pathways in patients with metastatic osteosarcoma may provide new strategies to enhance tumor clearance and resistance to disease.
IDIOPATHIC APLASTIC ANEMIA WITH RECOVERY
Authors: George S. Mirick
Journal: Annals of Internal Medicine (1941)

Case Reports1 June 1941IDIOPATHIC APLASTIC ANEMIA WITH RECOVERYGEORGE S. MIRICK, M.D.GEORGE S. MIRICK, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-14-12-2307 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIt is well known that recovery from "idiopathic" aplastic anemia is extremely unusual. Wintrobe1 was able to find only six cases in his review of the literature. We report here a seventh cured case which we feel to be true idiopathic aplastic anemia.CASE REPORTA. T., a 30-year-old, married, white male, sugar refinery worker was admitted to the hospital on April 14, 1937. His presenting complaints were weakness and pallor for three months. The family history was negative. He had measles as a child, influenza in 1919, and a rather acute diarrhea for one week in 1927. He had...Reference1. WINTROBESTOWELLROLL MMARM: Report of a case of aplastic anemia following gold injections in which recovery occurred, Am. Jr. Med. Sci., 1939, cxcvii, 698. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: New York, N. Y.*Received for publication January 8, 1940.From the Department of Medicine, Stanford University School of Medicine, San Francisco, California. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byDie Panmyelophthise und verwandte Zustände der Knochenmarksinsuffizienz 1 June 1941Volume 14, Issue 12Page: 2307-2309KeywordsAcute diarrheaAplastic anemiaMeasles ePublished: 1 December 2008 Issue Published: 1 June 1941 PDF downloadLoading ...