tbuckley/cabot-search huggingface dataset:
Inflammation-induced endothelial dysfunction involves reduced nitric oxide bioavailability and increased oxidant stress
Authors: B CLAPP, A HINGORANI, R KHARBANDA, V MOHAMEDALI, J STEPHENS, P VALLANCE, R MACALLISTER
Journal: Cardiovascular Research (2004)

Our aim was to investigate mechanisms of inflammation-induced endothelial dysfunction in humans.Endothelial function in twenty-one healthy human volunteers was measured using forearm venous plethysmography before and 8 h after administration of typhoid vaccination to generate an inflammatory response. Basal and stimulated endothelial nitric oxide (NO) bioavailability was assessed by measurement of the responses to intra-arterial N(G)-monomethyl-l-arginine (l-NMMA) and bradykinin, respectively. The effects of supplementation with l-arginine or ascorbic acid were assessed to probe the effects of substrate deficiency and oxidative stress, respectively. Systemic effects were determined by measuring cytokine response, total anti-oxidant status (TAOS) and urinary protein excretion.Vaccination induced a cytokine response, a fall in total anti-oxidant status and increased urinary albumin excretion (UAE). There was a reduction in the response to bradykinin (BK, P<0.005) and l-NMMA (P<0.0001) with no effect on the response to glyceryl trinitrate (GTN) and norepinephrine (NE). Following vaccination blood flow response to BK (but not GTN) was partially returned to pre-vaccine levels by infusion of ascorbic acid (P=0.01). Supplementation with l-arginine had no effect.Inflammation causes widespread endothelial dysfunction, reduces vascular NO bioavailability and increases oxidative stress. These actions are partially reversible with local anti-oxidants. These findings suggest a role for reactive oxygen species in inflammation-induced endothelial dysfunction.
A Growing Problem
Authors: Wendy W. Yeh, Sanjay Saint, Steven E. Weinberger
Journal: New England Journal of Medicine (2007)

A 36-year-old pregnant woman at 21 weeks' gestation presented with a 4-week history of a dry, nonproductive cough. She said she had no fever, chills, dyspnea, chest pain, or weight loss. She had no new pets, environmental exposures, or sick contacts.
Aortic input impedence and neurohormonal activation in patients with mild to moderate chronic congestive heart failure
Authors: E. P Kromer, D. Eisner, S. R Holmer, A. Muntze, G. A J Riegger
Journal: Cardiovascular Research (1992)

The aim was to investigate the interrelation between pulsatile components (assessed by determination of aortic input impedance) and neurohormonal activation in chronic congestive heart failure.Aortic input impedance, plasma noradrenaline, renin, atrial natriuretic factor, and arginine vasopressin were measured in 20 patients with mild to moderate chronic congestive heart failure (coronary artery disease n = 12, idiopathic dilated cardiomyopathy n = 8).Cardiac index [2.2(SEM 0.3) litre.min-1.m-2] and left ventricular ejection fraction [38(4)%] were reduced, and pulmonary wedge pressure was increased [21(2) mmHg]. Plasma concentrations of noradrenaline [462(62) pg.ml-1], renin [12(4) ng AI.ml.h-1], atrial natriuretic factor [408(64) pg.ml-1], and--to a slight degree--arginine vasopressin [1.1(0.3) pg.ml-1] were increased. Characteristic impedance Zc [80(6) dyne.s.cm-5) and relative oscillatory aortic input pressure power [10(1)%]--both reflecting the pulsatile components of left ventricular afterload--were within the normal range. There was no significant correlation between these variables and the degree of neurohormonal activation (r values: -0.05 to -0.35).The data show that in patients with mild to moderate chronic congestive heart failure there is no interrelationship between the degree of neurohormonal activation and pulsatile components of left ventricular afterload. This may indicate that in these stages of heart failure there are no trophic effects of stimulated neurohormonal systems on the physical properties of the great arteries.
McGonigle's Foot
Authors: Jack Coulehan
Journal: JAMA (1995)

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
Government is still "listening" as NHS Future Forum continues work
Authors: J. Carlowe
Journal: BMJ (2011)

Doctors’ and managers’ bodies have welcomed news that the NHS Future Forum is to continue.

The government announced that the independent group, led by the GP Steve Field, would continue its “listening exercise” on the future of the NHS in England and would expand its remit to include education and training, information, integrated care, and public health.

Professor Field said, “If we want the health and care system to change and meet the challenges of the future, then it is essential that we make sure that the thoughts and concerns of clinicians and, importantly, patients and service users, are listened to. …
Prospective Oral Mucositis Audit: Oral Mucositis in Patients Receiving High-Dose Melphalan or BEAM Conditioning Chemotherapy—European Blood and Marrow Transplantation Mucositis Advisory Group
Authors: Nicole Blijlevens, Matthias Schwenkglenks, Pamela Bacon, Alessandra D'Addio, Hermann Einsele, Johan Maertens, Dietger Niederwieser, Werner Rabitsch, Ann Roosaar, Tapani Ruutu, Harry Schouten, Rebecca Stone, Samuel Vokurka, Barry Quinn, Shaun McCann
Journal: Journal of Clinical Oncology (2008)

The Prospective Oral Mucositis Audit assessed the incidence, duration, and determinants of severe oral mucositis (OM; WHO oral toxicity scale grades 3 to 4) in patients with multiple myeloma (MM) or non-Hodgkin's lymphoma (NHL) receiving high-dose conditioning chemotherapy before autologous stem-cell transplantation.Patients with MM (n = 109; mean age, 57 +/- 8 years) or NHL (n = 88; mean age, 50 +/- 13 years) were treated with high-dose melphalan (200 mg/m(2)) or carmustine 300 mg/m(2), etoposide 800 mg/m(2), cytarabine 800 to 1,600 mg/m(2), and melphalan 140 mg/m(2) chemotherapy, respectively, in 25 European centers. OM assessments were made daily until 30 days after transplantation or hospital discharge. High quality of OM assessment was ensured by an intensive training program.Severe OM occurred in 46% (95% CI, 36% to 56%) of patients with MM and 42% (95% CI, 32% to 53%) of patients with NHL, with a mean duration of 5.3 days (95% CI, 4.4 to 6.1 days) and 5.5 days (95% CI, 4.5 to 6.7 days), respectively. Time from start of conditioning to peak OM score was 12.1 +/- 2.6 and 14.6 +/- 2.4 days. Severe OM risk and/or duration was significantly associated with higher chemotherapy dose per kilogram of body weight and poor performance status, but in contrast with some previous reports, this was not related to age.Severe OM is more common in the transplantation setting than previously reported, justifying effective preventative and therapeutic measures.
Optimal Treatment of Obesity-Related Hypertension
Authors: Jürgen Scholze, Elmar Grimm, Dana Herrmann, Thomas Unger, Ulrich Kintscher
Journal: Circulation (2007)

Current guidelines for the treatment of hypertension do not provide specific recommendations for obese hypertensive patients. To identify an optimal treatment regimen for obese hypertensive patients, we studied the interactions between a drug-based weight loss approach by sibutramine and different antihypertensive drug regimens.This was a prospective, 16-week double-blind placebo-controlled randomized multicenter study in 171 obese hypertensive patients. After a 2-week run-in period, patients receiving 1 of the 3 antihypertensive combination therapies (felodipine 5 mg/ramipril 5 mg [n=57], verapamil 180 mg/trandolapril 2 mg [n=55], or metoprolol succinate 95 mg/hydrochlorothiazide 12.5 mg [metoprolol/hydrochlorothiazide; n=59]) were assigned randomly to sibutramine (15 mg) or placebo. Sibutramine treatment resulted in a significantly greater decrease in body weight, body mass index, and waist circumference and a significant increase in diastolic blood pressure during 24-hour blood pressure monitoring compared with placebo treatment. Sibutramine-induced weight loss and reduction of visceral obesity were markedly attenuated in the metoprolol/hydrochlorothiazide group compared with the other groups. Consistently, improvement in glucose tolerance and hypertriglyceridemia by sibutramine was abrogated in the cohort treated with metoprolol/hydrochlorothiazide compared with the other groups.The present study demonstrates for the first time that an antihypertensive combination therapy regimen with angiotensin-converting enzyme inhibitors and calcium channel blockers is more advantageous than a beta-blocker/diuretic-based regimen in supporting the weight-reducing actions and concomitant metabolic changes induced by sibutramine in obese hypertensive patients. These data may help to develop future comprehensive treatment strategies and guidelines for this high-risk patient population.
Oxidative stress as a trigger for cellular immune responses in patients with alcoholic liver disease
Authors: Stephen F. Stewart, Matteo Vidali, Christopher P. Day, Emanuele Albano, David E.J. Jones
Journal: Hepatology (2004)

Serum antibodies reactive with neo-antigens generated during ethanol metabolism have been identified in patients with alcoholic liver disease (ALD), although their role in the pathogenesis of disease remains unclear. In this study, we characterized peripheral blood mononuclear cell (PBMC) T-cell and antibody responses to human serum albumin (HAS) adducted with acetaldehyde under reducing conditions (AcA-HSA) or with malondialdehyde (MDA-HSA) in patients with advanced ALD (AALD, n = 28), heavy drinkers with no liver disease (NALD, n = 14), and mild/moderate drinking controls ( n = 22). Peak proliferative responses of PBMC were assessed in vitro by tritiated thymidine incorporation after the addition of optimized concentrations of antigen or OKT3. Antibody titers were determined by enzyme-linked immunosorbent assay (ELISA). MDA-HSA induced PBMC T-cell proliferation was significantly higher in ALD than in NALD or control patients. Moreover, 10 of 28 (36%) of ALD patients had significant T-cell proliferative responses to MDA-HSA compared to 0 of 14 (0%, P = .02) of the NALD group and 2 of 22 (9%, P &lt; .05) of controls. No significant difference in PBMC T-cell response to Aca-HSA was seen between subject groups. Patients with positive cellular responses to MDA had higher serum anti-MDA antibody titers than those not exhibiting a positive cellular response ( P &lt; .005). In conclusion, the pattern of cellular and humoral responses to MDA adducts suggests that the development of these responses may be a susceptibility factor for the development of advanced alcoholic liver disease. The apparent importance of T-cell responses to MDA adducts suggests that oxidative stress may represent an important stimulus for the development of cellular immune responses associated with advanced ALD. (Hepatology 2004;39:197-203.)
Relationship Between BMI and Age at Diagnosis of Type 1 Diabetes in a Mediterranean Area in the Period of 1990–2004
Authors: Marga Giménez, Eva Aguilera, Conxa Castell, Nuria de Lara, Joana Nicolau, Ignacio Conget
Journal: Diabetes Care (2007)

In 2001, Wilkin (1) postulated that type 1 and type 2 diabetes are mostly the same disorder, only distinguished by the rate of β-cell loss with three different accelerators participating in the process (2,3).

Since 2002, many articles have supported the “accelerator hypothesis,” showing that BMI and changes in weight are inversely related to age at diagnosis of type 1 diabetes (4–6). Recently, Knerr et al. (7), in a large cohort of children with type 1 diabetes, concluded that a higher BMI was associated with a younger age at diagnosis of type 1 diabetes and that an increased weight gain could be considered a risk factor for early manifestation of the disease. Dabelea et al. (8) concluded that increasing BMI is associated with younger age at diagnosis only in subjects with a reduced β-cell function and hypothesized that obesity is accelerating the onset of type 1 diabetes at a higher stage in the natural history of the disease, after substantial autoimmune destruction of the β-cell has occurred. However, as expected, other studies did not agree with the postulate (9).

Until now, the data testing the accelerator hypothesis comes almost exclusively from Anglo-Saxon and central European populations. The aim of our study was to investigate the relationship between BMI and the age at onset of type 1 diabetes in a large cohort of Mediterranean subjects in whom diabetes became manifest between 1990 and 2004.

We analyzed data on 3,203 subjects (1,836 male, 2–24 years of age at diagnosis) with newly diagnosed type 1 diabetes included in the Catalan Registry database for new cases of type 1 diabetes between 1990 and 2004 (10). Data on BMI corresponded to information obtained during the 1st week after the diagnosis. The patients were classified into five groups according to …
Conservative surgery of the mitral valve in bacterial endocarditis.
Authors: M D Gammage, W A Littler, L D Abrams
Journal: Thorax (1984)

<h3>Aims</h3> <h3>Background</h3> Heart murmurs in a new born are common due to transition from fetal circulation to neonatal circulation. Majority of these heart murmurs disappear in few days, but they can also be a sign of underlying congenital heart disease. In UK the practice in majority of neonatal units is, heart murmur in an asymptomatic new born with normal examination and passing pulseOx, is reviewed again by middle grade after 24 hours. If the murmur is innocent (Grade 1-2/6, no signs or symptoms) then baby is brought back to neonatal clinic in 4 -6 weeks for follow-up. Due to the Covid pandemic in March 2020 our unit policy changed for all innocent murmurs to be followed up by the GP at 6 – 8 weeks. <h3>Objective</h3> To assess the outcome of change in policy of heart murmur follow-up during the pandemic. <h3>Methods</h3> A retrospective study from March 2020 – June 2021 (15 months). Data collected of infants who had a heart murmur on routine newborn examination, using NIPE Smart data, admission notes, Badger and postnatal notes. Infants discharged for GP follow up as per revised guideline were identified, and parents of these infants were contacted to enquire about GP follow up and the outcome. <h3>Results</h3> During the audit period, 101 infants were found to have a heart murmur on routine neonatal examination. Of these 101: • 72 had resolved on middle grade review after 24 hours • 11 received inpatient ECHO before discharge. • 18 were discharged for GP review at 6-8 weeks. 17 of 18 parents of these infants were contacted, with one baby excluded due to incorrect data. 16 were aware of the heart murmur at the time of discharge. 17/17 (100%) patients contacted had a GP review at 6-8 weeks as planned. At this review, the murmur persisted in 4/17 (24%) infants. One of these infants was re-reviewed by the GP and subsequently resolved, and a further two infants were referred to paediatrics for ECHO. The final infant was not referred or re-reviewed, but has remained clinically well. <h3>Conclusion</h3> All infants discharged for GP follow up were reviewed, and all have remained clinically well since discharge. Murmur had resolved in the majority of infants. Where the murmur persisted, the infant was appropriately referred or re-reviewed in the majority of cases. Asymptomatic infants with low grade (likely innocent) murmurs, we can continue to discharge home with GP follow-up.
Clozapine for Treatment of Schizophrenia
Authors: Robert D. Orr
Journal: JAMA (1996)

<h3>To the Editor.</h3> —In an article in the series Grand Rounds at the Clinical Center of the National Institutes of Health, Drs Pickar and Hsiao<sup>1</sup>reported a selected patient who participated in a double-blind clinical trial showing that clozapine is effective in the treatment of refractory schizophrenia. The research protocol used placebos. While some authors attempt to justify the use of placebo controls in clinical trials for schizophrenia,<sup>2</sup>others condemn placebo usage when effective treatment is known.<sup>3</sup> Although their case report is not intended to be a report of the research, their allusion to the study without citation raises some important questions. The authors report, "Placebo substitution was followed by rapid increases in symptoms of schizophrenia." Was this psychotic patient able to give valid consent? Did she clearly understand that she would be on no treatment for some period of time? How long was this patient's condition
Ambient PM <sub>2.5</sub> Exposure Up-regulates the Expression of Costimulatory Receptors on Circulating Monocytes in Diabetic Individuals
Authors: Alexandra Schneider, Neil E. Alexis, David Diaz-Sanchez, Lucas M. Neas, Shirley Harder, Margaret C. Herbst, Wayne E. Cascio, John B. Buse, Annette Peters, Robert B. Devlin
Journal: Environmental Health Perspectives (2010)

Exposure of humans to air pollutants such as ozone and particulate matter (PM) may result in airway and systemic inflammation and altered immune function. One putative mechanism may be through modification of cell-surface costimulatory molecules.We examined whether changes in expression of costimulatory molecules on circulating cells are associated with ambient levels of fine PM [aerodynamic diameter ≤ 2.5 μm (PM2.5)] in a susceptible population of diabetic individuals.Twenty subjects were studied for 4 consecutive days. Daily measurements of PM2.5 and meteorologic data were acquired on the rooftop of the exam site. Circulating cell-surface markers that mediate innate immune and inflammatory responses were assessed by flow cytometry on each day. Sensitivity analysis was conducted on glutathione S-transferase M1 (GSTM1) genotype, body mass index, and glycosylated hemoglobin A1c (HbA1c) levels to determine their role as effect modifiers. Data were analyzed using random effects models adjusting for season, weekday, and meteorology.We found significantly increased monocyte expression (mean fluorescent intensity) of CD80, CD40, CD86, HLA-DR, and CD23 per 10-μg/m3 increase in PM2.5 at 2- to 4-day lag times after exposure. These findings were significantly higher in obese individuals, in individuals with HbA1c > 7%, and in participants who were GSTM1 null.Exposure to PM2.5 can enhance antigen-presenting cell phenotypes on circulating cells, which may have consequences in the development of allergic or autoimmune diseases. These effects are amplified in diabetic individuals with characteristics that are associated with insulin resistance or with oxidative stress.
Comparison of the 'open' vs 'closed' intensive care unit formats
Authors: G. Wittig
Journal: JAMA (1996)

To the Editor.  —The article by Carson et al1strongly implies that care was better under the closed ICU system because of a nonsignificant trend in mortality. One could just as easily conclude otherwise; the mortality among patients requiring mechanical ventilation was higher (46.8% vs 34%) under the closed system. Intensive care unit nurses felt more comfortable working solely with dedicated ICU physician staff, but this is only to be expected and does not make a valid outcome measure. I suspect the greater mean APACHE II score of patients during the closed trial reflected reluctance among primary physicians to relinquish care of borderline patients to the ICU staff. One wonders if net hospital mortality did not increase among relatively sick patients kept in the regular medical units. Mandating the transfer of ICU patients to critical care specialists may improve short-term outcomes; as a primary care physician, I am well aware of my
Overexpression of ADAM9 in Non-Small Cell Lung Cancer Correlates with Brain Metastasis
Authors: Yasushi Shintani, Shigeki Higashiyama, Mitsunori Ohta, Hirohisa Hirabayashi, Sakae Yamamoto, Tatsuya Yoshimasu, Hikaru Matsuda, Nariaki Matsuura
Journal: Cancer Research (2004)

The "a disintegrin and metalloprotease" (ADAM) family contributes to regulation of the cell-cell and cell-matrix interactions that are critical determinants of malignancy. To determine the relationship between metastasis and ADAM proteins, we compared the mRNA levels of ADAM9, -10, -12, -15, and -17 in sublines of an EBC-1 lung cancer cell line that were highly metastatic to either brain or bone. ADAM9 mRNA levels were significantly higher in highly brain-metastatic sublines than in the parent or highly bone-metastatic sublines. To elucidate the role of ADAM9 in brain metastasis, we stably transfected A549 and EBC-1 cells with a full-length ADAM9 expression vector. Compared with mock-transfectants, ADAM9 overexpression resulted in increased invasive capacity in response to nerve growth factor, increased adhesion to brain tissue, and increased expression of integrin alpha 3 and beta 1 subunits. Administration of the anti-beta 1 monoclonal antibody attenuated this increase in invasive and adhesive activity. Intravenous administration of ADAM9-overexpressing A549 cells to mice resulted in micrometastatic foci in the brain and multiple metastatic colonies in the lungs. In contrast, administration of parent and mock-transfected A549 cells to mice resulted in lung tumors without brain metastasis. These results suggest that ADAM9 overexpression enhances cell adhesion and invasion of non-small cell lung cancer cells via modulation of other adhesion molecules and changes in sensitivity to growth factors, thereby promoting metastatic capacity to the brain.
Laryngotracheal Damage After Prolonged Use of Orotracheal Tubes in Adults
Authors: Michael Hedden
Journal: JAMA (1969)

Laryngotracheal damage after prolonged retention of orotracheal tubes (one to ten days) in adults was reviewed in 116 unselected patients admitted to an intensive care unit. Among the 59 survivors, all patients who had the tube in place for more than 48 hours had temporary difficulties with orally taken fluids for several hours after extubation. In two of five survivors having the tube in place for more than 72 hours, hoarseness (two patients) and aspiration (one patient) were irreversible. In 27 of 57 patients who died, the larynges and tracheas were examined and scored postmortem for lesions. Scores increased with duration of intubation. Retention of tracheal tubes for less than 72 hours was rarely followed by serious lesions. Six of seven patients who had the tube in place for more than 72 hours showed high scores.