tbuckley/cabot-search huggingface dataset:
Striking In Vivo Phenotype of a Disease-Associated Human <i>SCN5A</i> Mutation Producing Minimal Changes in Vitro
Authors: Hiroshi Watanabe, Tao Yang, Dina Myers Stroud, John S. Lowe, Louise Harris, Thomas C. Atack, Dao W. Wang, Susan B. Hipkens, Brenda Leake, Lynn Hall, Sabina Kupershmidt, Nagesh Chopra, Mark A. Magnuson, Naohito Tanabe, Björn C. Knollmann, Alfred L. George, Dan M. Roden
Journal: Circulation (2011)

Background— The D1275N SCN5A mutation has been associated with a range of unusual phenotypes, including conduction disease and dilated cardiomyopathy, as well as atrial and ventricular tachyarrhythmias. However, when D1275N is studied in heterologous expression systems, most studies show near-normal sodium channel function. Thus, the relationship of the variant to the clinical phenotypes remains uncertain. Methods and Results— We identified D1275N in a patient with atrial flutter, atrial standstill, conduction disease, and sinus node dysfunction. There was no major difference in biophysical properties between wild-type and D1275N channels expressed in Chinese hamster ovary cells or tsA201 cells in the absence or presence of β1 subunits. To determine D1275N function in vivo, the Scn5a locus was modified to knock out the mouse gene, and the full-length wild-type (H) or D1275N (DN) human SCN5A cDNAs were then inserted at the modified locus by recombinase mediated cassette exchange. Mice carrying the DN allele displayed slow conduction, heart block, atrial fibrillation, ventricular tachycardia, and a dilated cardiomyopathy phenotype, with no significant fibrosis or myocyte disarray on histological examination. The DN allele conferred gene-dose–dependent increases in SCN5A mRNA abundance but reduced sodium channel protein abundance and peak sodium current amplitudes (H/H, 41.0±2.9 pA/pF at −30 mV; DN/H, 19.2±3.1 pA/pF, P &lt;0.001 vs H/H; DN/DN, 9.3±1.1 pA/pF, P &lt;0.001 versus H/H). Conclusions— Although D1275N produces near-normal currents in multiple heterologous expression experiments, our data establish this variant as a pathological mutation that generates conduction slowing, arrhythmias, and a dilated cardiomyopathy phenotype by reducing cardiac sodium current.
The effect of flexible settings on participation rates, data quality, and costs in a longitudinal study of ethnically diverse young adults: the London Determinants of young Adult Social wellbeing and Health (DASH) study
Authors: Seeromanie Harding, Zinat Ellaheh Enayat, Aidan Cassidy, Ursula M Read, Catherine Ferrell, Oarabile Ruth Molaodi
Journal: The Lancet (2013)
Foreign Medical Graduates and Their Surgical Training
Authors: Harris B. Shumacker
Journal: JAMA (1961)

THE OCCURRENCE of a second world war. within the span of one generation brought about among many of us not only a starkly realistic appreciation of the horror, waste, and futility of war, but also a sincere desire to do everything possible to avert another. The widespread deployment of our military personnel around the globe, the warmth with which we were received by our allies, the ease with which stimulating and often lasting friendships were made, and especially the understanding brought about by such travel and intermingling made it evident that here lay a fruitful avenue for building a true basis for peaceful international cooperation. These events came about at a time when many of the peoples of the world were looking upon our nation as the leader in the field of medicine. A great opportunity was suddenly ours. Thousands of fledgling physicians and surgeons turned to us for opportunities
Soluble CD27 Levels in Children with Acute and Chronic Renal Failure
Authors: T. Kendirli, A. İkincioğullari, M. Ekim, F. Doğu, F. Yalçınkaya, S. Yüksel, Z. Özçakar, D. Güloğlu, B. Doğanay, E. Babacan
Journal: Journal of Allergy and Clinical Immunology (2009)
Prospective Risk Assessment of Endoscopic Retrograde Cholangiography in Patients with Primary Sclerosing Cholangitis
Authors: S. J. van den Hazel, F. H. J. Wolfhagen, H. R. van Buuren, P. C. van de Meeberg, D. J. van Leeuwen, representing the Dutch PSC study group
Journal: Endoscopy (2000)

Direct endoscopic retrograde cholangiopancreatography (ERCP) has become the standard for establishing the diagnosis of primary sclerosing cholangitis (PSC), while endoscopic procedures play an increasingly important therapeutic role. However, many believe that this procedure carries a significant risk of infection and other complications. We assessed the incidence of complications within 1 week of ERCP in patients with PSC.In a multicenter study, patients who underwent ERCP for (suspected) PSC were prospectively followed for the occurrence of complications after the procedure.A total of 106 ERCPs performed in 83 patients were evaluated. Complications occurred on ten occasions (9%): pancreatitis (n = 3), cholangitis (n = 2), increase of cholestasis (n = 2), postsphincterotomy bleeding (n = 1), cystic duct perforation (n = 1), and venous thrombosis (n = 1). All complications resolved quickly with proper therapy. Complications were more likely when ERCP was done to evaluate specific complaints such as jaundice or recurrent cholangitis (9/59) than after a purely diagnostic ERCP (1/47 relative risk [RR] 7.2, 95% confidence interval [CI] 1.00 to 153). Therapeutic interventions performed during ERCP (e.g. placement of endoprosthesis, dilation of strictures) also increased the risk of postprocedural complications (RR 4.5, 95 % CI 0.94 to 30).ERCP is a safe method for establishing the diagnosis of PSC in asymptomatic patients (2 % complication rate). Although ERCP in symptomatic patients carries a higher risk (14%), this can be justified by the benefits of endoscopic therapy.
Lack of correlation between hepatitis C virus genotypes and clinical course of hepatitis C virus-related cirrhosis
Authors: L Benvegnù
Journal: Hepatology (1997)

The influence of the hepatitis C virus (HCV)-genotype on liver disease severity was evaluated in 429 consecutive patients with chronic hepatitis C, including 109 with cirrhosis who were followed up prospectively, allowing for the assessment of the role of the HCV-genotype on disease outcome and on the development of hepatocellular carcinoma (HCC). HCV-1 was detected in 147 (46%) patients without cirrhosis and in 47 (43%) with cirrhosis (P: not significant), being mainly HCV-1b. HCV-2 was found in 103 (32%) cases without cirrhosis and in 30 (27.5) with cirrhosis (P: not significant), being mainly HCV-2a. HCV-3 was detected in 32 (10%) patients without cirrhosis and in 2 (2%) with cirrhosis (P < 0.005). Infection with more than one genotype (HCV-1/HCV-2 and HCV-1/HCV-3) was observed only in cirrhotic patients (6 of 109; 5.5%). During a mean follow-up of 67 +/- 22 months, 21 (19%) patients with cirrhosis showed worsening in Child's stage, 5 (4.5%) underwent liver transplantation, 23 (21%) developed HCC, and 24 (22%) died of complication of liver disease; the overall incidence of at least one of these events was 38.5%. By the Kaplan-Meier method and log-rank test, the cumulative probability of developing each or at least one of the above events did not differ in relation to the genotype of infecting HCV, apart from patients with mixed genotype infection who showed a significantly higher incidence of death (P < .05). These data indicate that HCV-genotypes do not have a significant effect on the severity and outcome of liver disease in patients with chronic HCV-infection. Patients with cirrhosis who are also infected by HCV-1 and HCV-2 had a similar prognosis and progression to HCC, while patients infected by more than one genotype showed the most unfavorable course of disease.
Bush's plan to screen for mental health meets opposition in Illinois
Authors: Jeanne Lenzer
Journal: BMJ (2004)

the commercial sector (mainly the pharmaceutical industry), but the public sector contributed 44%, a sizeable chunk of which comes from the US National Institutes of Health (NIH), where the budget soared from $11.9bn in 1996 to $23.3bn in 2003.New substantial private, not for profit sources of funding, foundations and charities, such as the Bill and Melinda Gates Foundation, have also played their part to the tune of 8%, says the report.But research and development continues to be dominated by just a few countries, with the United States accounting for 49% of the total spend, followed by Japan at 13% and the United Kingdom at 7%.
Long distance travel for routine elective surgery: questionnaire survey of patients' attitudes.
Authors: G P Howell, D Richardson, A Forester, J Sibson, J M Ryan, B T Morgans
Journal: BMJ (1990)

To carry out an audit and assess the acceptability of long distance travel to patients on a lengthy surgical waiting list.Audit and questionnaire survey.Military hospital in Wiltshire.116 Patients on a general surgical waiting list at Leighton Hospital near Crewe.Preselection for medical fitness at a waiting list review clinic.Roughly half of patients offered the facility of travelling 120 miles (190 km) for their routine elective operation at the health authority's expense accepted. The average waiting list time declared by the patients who travelled was 28 months, and 13 patients stated that their condition prevented them from working. Only four patients regretted their decision to participate in the scheme. Lack of visitors did not cause undue concern.Some patients did not agree to travel for their operation but almost all of those who did so found the scheme satisfactory. Some minor problems were encountered but these could probably be overcome by ensuring use of appropriate transport, extending the postoperative stay when necessary, and more careful selection of patients for an anaesthetic. For efficient use of theatre time in such schemes it is crucial that the operating consultant surgeon should be in charge of case selection.
LARYNGISMUS DUE TO A CONGENITAL VALVULAR FORMATION OF THE UPPER ORIFICE OF THE LARYNX.Read in the Section of Laryngology and Otology, at the Forty-second Annual Meeting of the American Medical Association, held at Washington, D. C., May, 1891.
Authors: J. H. BRYAN
Journal: JAMA (1891)

In this short communication it is my purpose to call attention only to that form of spasm of the infantile larynx due to a congenital valvular formation of the upper orifice of the larynx, a condition that is sometimes overlooked as a cause of noisy respiration in children. In these cases there is a laryngismus of a mild variety, and as it is so very persistent, it is evident that it must depend upon some local cause. The subjects of this condition may be perfectly healthy, showing no evidences of rickets or glandular enlargement—the most common causes of that severe form of laryngeal spasm known as laryngismus stridulous. There is no tendency to convulsions, and the respiration is noisy, or reedy, as described by some, being at times quite labored. The spasm is more persistent than in the severer forms of laryngismus, being present to some extent during sleep, and
Cross-presentation of antigen by diverse subsets of murine liver cells
Authors: Mohammad R. Ebrahimkhani, Isaac Mohar, Ian N. Crispe
Journal: Hepatology (2011)

Antigen cross-presentation is a principal function of specialized antigen-presenting cells of bone marrow origin such as dendritic cells. Although these cells are sometimes known as "professional" antigen-presenting cells, nonbone marrow-derived cells may also act as antigen-presenting cells. Here, using four-way liver cell isolation and parallel comparison of candidate antigen-presenting cells, we show that, depending on the abundance of antigen-donor cells, different subsets of liver cells could cross-present a hepatocyte-associated antigen. This function was observed in both liver sinusoidal endothelial cells and Kupffer cells even at very low antigen concentration, as well as when using soluble protein. Antigen cross-presentation by liver cells induced efficient CD8+ T-cell proliferation in a similar manner to classical dendritic cells from spleen. However, proliferated cells expressed a lower level of T-cell activation markers and intracellular interferon-gamma levels. In contrast to classical spleen dendritic cells, cross-presentation by liver antigen-presenting cells was predominantly dependent on intercellular adhesion molecule-1.Hepatic sinusoids are an environment rich in antigen cross-presenting activity. However, the liver's resident antigen-presenting cells cause partial T-cell activation. These results clarify how the liver can act as a primary site of CD8+ T-cell activation, and why immunity against hepatocyte pathogens is sometimes ineffective.
Review of Generic Bioequivalence Studies
Authors: Jane E. Henney
Journal: JAMA (1999)

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
Dissociation of systemic and renal effects in endotoxemia. Prostaglandin inhibition uncovers an important role of renal nerves.
Authors: W L Henrich, Y Hamasaki, S I Said, W B Campbell, R E Cronin
Journal: Journal of Clinical Investigation (1982)

To elucidate the mechanisms responsible for systemic and renal hemodynamic changes in early endotoxemia, the roles of prostaglandins (PG) and renal nerves were investigated. Endotoxin (E, 3 micrograms/kg i.v.) was given to two groups of anesthetized dogs that had undergone unilateral renal denervation: Group I (n = 9) E only; Group II (n = 11) E + indomethacin (10 mg/kg i.v.) or meclofenamate (5 mg/kg i.v.). A third group of dogs (Group III, n = 5) received indomethacin (10 mg/kg i.v.) only. 1 h after E group I dogs, mean arterial pressure (MAP) decreased from 126 to 94 mm Hg (P less than 0.001), and prostacyclin (6-keto-Fl alpha metabolite, PGI2) increased (from 0.64 to 2.08 ng/ml, P less than 0.005). Glomerular filtration rate (GFR) and renal blood flow (RBF) declined comparably both in innervated and denervated kidneys. In marked contrast, group II dogs had a stable MAP (136-144 mm Hg, NS) and no increase in PGI2 levels. Plasma renin activity (0.7-2.5 ng/ml per h, P less than 0.005) increased, and renin secretion was greater in innervated compared with denervated kidneys (255 vs. 74 U/min, P less than 0.01) in these PG-inhibited dogs. In addition, denervated kidneys in group II dogs had a greater GFR (42 vs. 34 ml/min, P less than 0.01) and RFB (241 vs. 182 ml/min, P less than 0.01) than innervated kidneys after E. Group III animals had no significant changes in systemic or renal hemodynamics, plasma renin activity or PGI2 during the study. These results suggest that PGI2 mediates the systemic hypotension of early endotoxemia in the PG-intact animal. Moreover, PG inhibition uncovers an important effect of E to increase efferent renal nerve activity with a consequent decline in GFR and RBF independent of changes in MAP. Finally, the results demonstrate that renal nerves are important stimuli to renin secretion in early endotoxemia via pathways that are PG-independent.
Antibiotic-Resistant “Superbugs” May Be Transmitted From Animals to Humans
Authors: Bridget M. Kuehn
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
Patients' attitudes to induction and labour.
Authors: P Stewart
Journal: BMJ (1977)

An attempt was made to ascertain patients' attitudes towards planned induction and labour. Twenty per cent of patients had not heard of induction before their pregnancy, and those who had had most probably heard about it from relations and friends rather than the media. Most patients had no firm opinions on induction of labour but were usually glad to have their pregnancy ended. Many considered that they had not been given enough information by the medical staff on their induction. The amount of pain experienced by patients at amniotomy was related to the "favourability" of the cervix. Possibly women with a low cervical score should be given more premedication or inhalation analgesia at amniotomy. Most patients found injections of narcotic agents adequate analgesia in labour. Those patients who did not receive adequate analgesia were principally those who had either very short or quite long labours. Patients with long labours may benefit from more liberal use of analgesia, but no satisfactory form of analgesia seems to be available for patients who are likely to deliver within two or three hours of induction.
Abstract P3-09-11: Acupuncture for the treatment of lymphedema in breast cancer patients: A pilot study in Korean women
Authors: YJ Jeong, MS Kim, JI Jang, JG Bong, SH Park, HJ Kwon, YS Park, OC Kwon, IH Shin
Journal: Cancer Research (2013)

Abstract Purpose: Lymphedema is a troublesome complication of breast cancer treatment. Recent studies suggest that acupuncture is effective in improving lymphedema in breast cancer patients. The purpose of this study was to assess the feasibility and safety of acupuncture for treatment of lymphedema in Korean breast cancer patients. Methods: This was a prospective, single-arm, observational study. Participants received 18 sessions of acupuncture, delivered 3 times a week for 6 weeks. Patients were evaluated 1 week before treatment commenced (baseline), once a week during treatment, and 4 weeks after the final acupuncture session. Recruitment was performed from September 2012 through December 2012, and 9 breast cancer patients presenting with lymphedema of the upper limb ipsilateral to surgery were enrolled. The primary outcome measure was severity of lymphedema assessed by stages of lymphedema, visual analogue scale (VAS) and circumferential measurements of the upper extremity. The secondary outcome measure was quality of life assessed by a self-administered questionnaire using the SF-36 Questionnaire. Results: Acupuncture significantly reduced the severity of lymphedema assessed by VAS (p&amp;lt;0.001) as well as circumferential measurements of upper extremity (p&amp;lt;0.001). Four weeks after the final treatment, symptoms were not aggravated. SF-36 scores remained significant for health status at the end of treatment (p = 0.018). No serious adverse events occurred in 162 treatment sessions and during the 4-week follow-up period. Conclusions: Our results showed the feasibility and safety of acupuncture for the treatment of lymphedema in Korean breast cancer patients. These findings suggest that acupuncture is a useful complementary and alternative treatment for improvement of lymphedema itself and related symptoms in breast cancer patients. A randomized controlled prospective study with a larger sample size is required to clarify the efficacy of acupuncture for such patients in Korea. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-09-11.
Serum insulin and glucose response to graded exercise in adults. Part I: the influence of fitness status.
Authors: J. A. White, A. H. Ismail, C. A. Bradley
Journal: British Journal of Sports Medicine (1978)

The effect of acute exercise upon serum immunoreactive insulin levels (IRI) and serum glucose concentrations (GC) was studied in groups of middle-aged men of contrasting physical fitness status. Two groups of subjects, one active and one sedentary (both N = 11, mean age 44 years), performed a graded cycle ergometer exercise test in the post-absorptive state. Venous blood samples were taken at rest, during low and high work intensities, and after recovery. The response of serum IRI to exercise was similar in both groups of subjects with significant increases observed during exercise followed by a return to resting values during recovery. However, the magnitude of serum IRI response was lower in the active group. In contrast, the sedentary group demonstrated little or no change in serum GC during exercise, whereas significant increases in serum GC were observed during exercise in the active group.
Abstract IA8: Role of biomarkers in the early detection of lung cancer
Authors: Pierre P. Massion
Journal: Clinical Cancer Research (2012)

Abstract While lung cancer remains the leading cause of cancer-related death in the world with a 16% overall survival rate, we now know that early detection by low dose chest CT saves lives. The implementation of screening programs represents a huge challenge. Research is needed to address who will benefit from screening, for how long, and with what frequency we should screen. Using biomarkers to select the most at-risk population, to detect the disease while measurable and yet not clinically apparent, and to predict survival, has been the goal of many investigations. Recent advances in molecular strategies and analytical platforms including genomics, epigenomics, proteomics, and metabolomics, have identified increasing numbers of potential biomarkers. These molecular approaches are applied to a variety of samples collected by non invasive methods including blood, urine, exhaled breath condensate, bronchial specimens, saliva, and sputum. None have yet moved to the clinical setting. In this presentation, we will define clinical contexts where diagnostic biomarkers may have utility in the management of lung cancer, we will review the state of development of candidate diagnostic biomarkers, and finally, we will discuss critical aspects of study design in biomarkers research.
Mining exomic sequencing data to identify mutated antigens recognized by adoptively transferred tumor-reactive T cells
Authors: Paul F Robbins, Yong-Chen Lu, Mona El-Gamil, Yong F Li, Colin Gross, Jared Gartner, Jimmy C Lin, Jamie K Teer, Paul Cliften, Eric Tycksen, Yardena Samuels, Steven A Rosenberg
Journal: Nature Medicine (2013)