tbuckley/cabot-search huggingface dataset:
Serotonin receptor blockade improves distal perfusion after lower limb ischemia in the fatty Zucker rat
Authors: P JANIAK, P LAINEE, Y GRATALOUP, C LUYT, J BIDOUARD, J MICHEL, S OCONNOR, J HERBERT
Journal: Cardiovascular Research (2002)

Lower limb perfusion following arterial occlusion depends on the recruitment of collateral vessels. Blood flow through these collateral vessels may be jeopardized by hypersensitivity to vasoconstriction by serotonin (5-HT), as has been reported during hyperlipidemia and diabetes. Therefore the aim of this study was to determine the benefits of chronic treatment with SL65.0472, a mixed 5-HT(1B)/5-HT(2A) receptor antagonist, on lower limb ischemia in fatty fa/fa Zucker rats, a strain characterized by obesity, diabetes and hyperlipidemia. Comparison was made with lean control fa/+ Zucker rats.SL65.0472 (3 mg/kg/day, n=16) or its vehicle (n=20) were administered orally for 13 days to male fatty fa/fa Zucker rats submitted to lower limb ischemia. Hindlimb ischemia was induced unilaterally by resection of the left femoral and external iliac arteries and embolization of the left internal iliac artery with microspheres. Distal perfusion was measured under mild anesthesia by laser Doppler imaging of both feet. The perfusion deficit (Delta%) was calculated before and 3, 7 and 14 days after induction of hindlimb ischemia. Twenty-four hours after the last administration of SL65.0472, muscular partial oxygen pressure, iliac blood flows, maximal vasodilatory reserve and the vasoreactivity to 5-HT were measured in both limbs.Chronic administration of SL65.0472 improved the distal perfusion from day 3. At day 14, the deficit of perfusion was limited to -36+/-7% in SL65.0472-treated animals vs. -70+/-6% in the vehicle-treated group (P<0.001) and was accompanied by a significant improvement of partial oxygen pressure in the ischemic limb (SL65.0472: 10.4+/-3.9 mmHg vs. vehicle: 3.5+/-1.1 mmHg, P<0.05). Maximal vasodilatory reserve tended to increase from 2.2+/-0.4 ml/min in the vehicle-treated group to 3.8+/-0.6 ml/min after SL65.0472. SL65.0472 markedly reduced 5-HT-mediated vasoconstriction, which was enhanced in the hypoperfused limb, without altering arterial pressure. Induction of hindlimb ischemia led to the overexpression of both 5-HT(1B) and 5-HT(2A) receptors only in the hypoperfused skeletal muscle as assessed by semi-quantitative RT-PCR.These results suggest that the recruitment of collateral vessels after the induction of hindlimb ischemia is significantly impaired in obese fa/fa Zucker rats due to a persistent vasoconstriction mediated by 5-HT and involving stimulation of 5-HT(1B) and/or 5-HT(2A) receptors.
Cost Effectiveness of Statin Therapy for the Primary Prevention of Major Coronary Events in Individuals With Type 2 Diabetes
Authors: Michael Brandle, Mayer B. Davidson, David L. Schriger, Brett Lorber, William H. Herman
Journal: Diabetes Care (2003)

OBJECTIVE—To assess the cost and cost effectiveness of hydroxymethylglutaryl (HMG)-CoA reductase inhibitor (statin) therapy for the primary prevention of major coronary events in the U.S. population with diabetes and LDL cholesterol levels ≥100 mg/dl, especially in the population with LDL cholesterol levels 100–129 mg/dl. RESEARCH DESIGN AND METHODS—Analyses were performed using population estimates from National Health and Nutrition Examination Survey (NHANES)-III, cost estimates from a health system perspective, statin LDL-lowering effectiveness from pivotal clinical trials, and treatment effectiveness from the diabetic subgroup analysis of the Heart Protection Study. RESULTS—There are ∼8.2 million Americans with diabetes, LDL cholesterol levels ≥100 mg/dl, and no clinical evidence of cardiovascular disease. Each year, statin therapy could prevent ∼71,000 major coronary events in this population. In the subgroup with LDL cholesterol levels 100–129 mg/dl, the annual cost of statin treatment ranges from $600 to $1,000 per subject. In the population with LDL cholesterol levels ≥130 mg/dl, the annual cost ranges from $700 to $2,100. Annual incremental cost per subject, defined as the cost of statin treatment plus the cost of major coronary events with statin treatment minus the cost of major coronary events without statin treatment, ranges from $480 to $950 in the subgroup with LDL cholesterol levels 100–129 mg/dl and from $590 to $1,920 in the population with LDL cholesterol levels ≥130 mg/dl. CONCLUSIONS—Statin therapy for the primary prevention of major coronary events in subjects with type 2 diabetes and LDL cholesterol levels 100–129 mg/dl is affordable and cost effective relative to statin therapy in subjects with higher LDL cholesterol levels.
Macrophages Mediate Inflammation-Enhanced Metastasis of Ovarian Tumors in Mice
Authors: Toni M. Robinson-Smith, Idit Isaacsohn, Carol A. Mercer, Mingfu Zhou, Nico Van Rooijen, Nader Husseinzadeh, Molly M. McFarland-Mancini, Angela F. Drew
Journal: Cancer Research (2007)

Abstract The tumor microenvironment is known to have a profound effect on tumor progression in a highly context-specific manner. We have investigated whether peritoneal inflammation plays a causative role in ovarian tumor metastasis, a poorly understood process. Implantation of human ovarian tumor cells into the ovaries of severe combined immunodeficient mice resulted in peritoneal inflammation that corresponds temporally with tumor cell dissemination from the ovaries. Enhancement of the inflammatory response with thioglycolate accelerated the development of ascites and metastases. Suppression of inflammation with acetyl salicylic acid delayed ascites development and reduced tumor implant formation. A similar prometastatic effect for inflammation was observed when tumor cells were injected directly into the peritoneum of severe combined immunodeficient mice, and in a syngeneic immunocompetent mouse model. Inflammation-modulating treatments did not affect primary tumor development or in vitro tumor cell growth. Depletion of peritoneal macrophages, but not neutrophils or natural killer cells, reduced tumor progression, as assessed by ascites formation and peritoneal metastasis. We conclude that inflammation facilitates ovarian tumor metastasis by a mechanism largely mediated by macrophages, and which may involve stromal vascular endothelial growth factor production. The confirmation of these findings in immunocompetent mice suggests relevance to human disease. Identifying the mechanisms by which macrophages contribute to tumor metastasis may facilitate the development of new therapies specifically targeting immune cell products in the tumor microenvironment. [Cancer Res 2007;67(12):5708–16]
Incidence of pulmonary thromboembolism, infarction and haemorrhage in disseminated intravascular coagulation: a necroscopic analysis.
Authors: Y Katsumura, K Ohtsubo
Journal: Thorax (1995)

The pathological features of the lung in disseminated intravascular coagulation (DIC) have not been established. This study was carried out on lungs taken at necropsy to examine the incidence and extent of thromboembolism, infarction, and haemorrhage.The subjects were 87 patients whose illnesses were complicated by DIC and 64 patients who showed no abnormalities of blood coagulation in their terminal illness. The lungs were fixed by intrabronchial infusion of 10% formalin, cut into 5 mm thick slices, and each cut surface was carefully examined for macroscopic thromboembolism, infarction, and haemorrhage. Five tissue blocks per case were taken for quantitative analysis of microscopic thromboembolism.In the control group macroscopic thromboembolism was identified in 20 cases (31.3%), infarction in one, and haemorrhage also in one. Moreover, fibrin thrombosis was seen in 13 cases (20.3%) and microthromboembolism in 24 (37.5%). Of the 87 patients with DIC, thromboembolism was found in 51 cases (58.6%), infarction in six, haemorrhage in 14, microscopic fibrin thrombosis in 43 (49.4%), and microthromboembolism in 45 (51.7%). Macroscopic thromboembolism, haemorrhage, and fibrin thrombosis were found more often in the patients with DIC.In addition to fibrin thrombosis, macroscopic thromboembolism and haemorrhage were the main pathological findings in the lungs of patients dying with DIC. The frequency of pulmonary infarction increased in proportion to the frequency of thromboembolism.
Development and Internal Validation of a Nomogram Predicting the Probability of Prostate Cancer Gleason Sum Upgrading Between Biopsy and Radical Prostatectomy Pathology
Authors: Felix K.-H. Chun, Thomas Steuber, Andreas Erbersdobler, Eike Currlin, Jochen Walz, Thorsten Schlomm, Alexander Haese, Hans Heinzer, Michael McCormack, Hartwig Huland, Markus Graefen, Pierre I. Karakiewicz
Journal: European Urology (2005)
Insoluble and soluble immune complexes activate neutrophils by distinct activation mechanisms: changes in functional responses induced by priming with cytokines
Authors: G Fossati
Journal: Annals of the Rheumatic Diseases (2002)

<h3>Background:</h3> Because ethical decision making in the care of extremely preterm infants varies widely across Europe, the Swiss Society of Neonatology decided to publish its own guidelines on the care of infants born at the limit of viability in 2002. <h3>Objective:</h3> To examine the potential impact of the guidelines on survival rates, short-term complication rates and centre-to-centre outcome differences of extremely preterm infants (22–25 completed weeks). <h3>Design:</h3> Population-based, retrospective cohort study. <h3>Setting:</h3> All nine level III neonatal intensive care units (NICU) and affiliated paediatric hospitals in Switzerland. <h3>Patients:</h3> 516 extremely preterm infants born alive between 1 January 2000 and 31 December 2004. <h3>Main outcome measures:</h3> Delivery room and NICU mortality rates, survival to hospital discharge and incidence of short-term complications in survivors were assessed. To study the impact of the guidelines, two cohorts from two different time periods were compared (years 2000/2001, n = 220; years 2003/2004, n = 204) whereas patients born in the year of the publication (2002, n = 92) were excluded. For centre-to-centre comparisons, the entire population (n = 516) was analysed. <h3>Results:</h3> There was a significant increase in survival rates of extremely preterm infants from 31% to 40% (RR 1.24, 95% CI 1.02, 1.50) after the publication of the Swiss guidelines. This improvement was largely explained by significantly improved survival from 42% to 60% (p = 0.01) among infants born at 25 completed weeks because of decreased NICU mortality. Improved survival was not associated with statistically significant changes in the incidence of short-term complications. Despite national guidelines, considerable centre-to-centre outcome differences have persisted. <h3>Conclusions:</h3> The publication of the Swiss guidelines was followed by significantly improved survival of extremely preterm infants but had no impact on centre-to-centre differences.
Glycoprotein IIb/IIIa Inhibition in Percutaneous Coronary Interventions—Reply
Authors: Sanjiv Sharma, William Nyitray, Brijesh Bhambi
Journal: JAMA (2003)

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
CO2 response and pattern of breathing in patients with symptomatic hyperventilation, compared to asthmatic and normal subjects
Authors: J Hormbrey, M S Jacobi, C P Patil, K B Saunders
Journal: European Respiratory Journal (1988)

We studied six patients with symptomatic hyperventilation, using new techniques to quantify baseline variability of respiratory variables, and to assess CO2 sensitivity around the control point using a stimulus not detectable by the subject. We compared them with six normal subjects and six patients with mild asthma. Symptomatic hyperventilators had normal mean ventilation and end-tidal carbon dioxide tension (PETCO2) at rest. Asthmatic subjects had higher ventilation and lower PETCO2. Symptomatic hyperventilators had a larger number of sighs and abnormally wide fluctuations in baseline for inspiratory time, expiratory time, and PETCO2. These could not be explained by an abnormal ventilatory response to a transient CO2 input; the transient response near the control point was undoubtedly normal.
Gene Expression Profiling of Renal Cell Carcinoma
Authors: Min-Han Tan, Craig G. Rogers, Jeffrey T. Cooper, Jonathon A. Ditlev, Thomas J. Maatman, Ximing Yang, Kyle A. Furge, Bin Tean Teh
Journal: Clinical Cancer Research (2004)

Abstract Renal cell carcinoma (RCC) is a histologically diverse disease, with variable and often unpredictable clinical behavior. The prognosis worsens dramatically with the onset of clinical metastasis, and current regimens of systemic therapy yield only modest benefits for metastatic RCC. Gene expression profiling is a promising technique for refining the diagnosis and staging of RCC, as well as for highlighting potential therapeutic targets. We review the recent advances in expression profiling of RCC and discuss the clinical and biological insights obtained from these studies.
Immune Response of Hepatitis B Vaccine Among Persons With Diabetes
Authors: Sarah F. Schillie, Philip R. Spradling, Trudy V. Murphy
Journal: Diabetes Care (2012)

In October 2011, the Advisory Committee on Immunization Practices (ACIP) recommended hepatitis B vaccination for adults with diabetes in the United States (1). Serosurvey data from the 1999–2010 National Health and Nutrition Examination Survey found that noninstitutionalized adults aged ≥18 years with diabetes have an increased seroprevalence of past or current hepatitis B virus (HBV) infection (1). Outbreaks of hepatitis B in elderly persons with diabetes in long-term care facilities have been linked to diabetes care procedures (including blood glucose monitoring), with likely vehicles for transmission including spring-loaded finger-stick devices used on multiple patients and blood glucose testing meters that were not cleaned between uses on different patients.

In the U.S., hepatitis B vaccination is routinely recommended for infants, children, and adolescents. It also is recommended for adults at increased risk of HBV infection, including persons with end-stage renal disease or chronic liver disease, health care personnel, injection-drug users, and men who have sex with men (2–4). A hepatitis B vaccination series results in protection in a high proportion (>95%) of infants, children, and young adults (5). As with other vaccines, the efficacy of the hepatitis B vaccine progressively declines with advancing age, as well as with the presence of obesity and other comorbid conditions (6–12). Results of studies of the hepatitis B vaccine among persons with diabetes generally follow these patterns (13,14).

Primary hepatitis B vaccination usually consists of 3 (or 4) doses of 10 or 20 µg of recombinant hepatitis B surface antigen (HBsAg) protein administered intramuscularly into the deltoid muscle on a 0-, 1-, and 6-month schedule (Table 1). Alternative schedules are U.S.-approved for routine vaccination for specific ages and vaccine formulations, and they elicit dose-specific and final rates of seroprotection similar to those obtained on a 0-, 1-, and …
Severe refractory hypercalcaemia in HTLV-1 infection
Authors: C M. B Edwards, S. J E Edwards, R.-P. Bhumbra, T. A Chowdhury
Journal: Journal of the Royal Society of Medicine (2003)

In hypercalcaemia, exclusion of common causes such as hyperparathyroidism or disseminated malignancy is straight-forward. Matters become more difficult when no obvious cause can be found. A rare cause of refractory hypercalcaemia is adult T-cell leukaemia/lymphoma (ATLL) induced by human T-cell leukaemia virus type-1 (HTLV-1).
Methylphenidate and/or a Nursing Telephone Intervention for Fatigue in Patients With Advanced Cancer: A Randomized, Placebo-Controlled, Phase II Trial
Authors: Eduardo Bruera, Sriram Yennurajalingam, J. Lynn Palmer, Pedro E. Perez-Cruz, Susan Frisbee-Hume, Julio A. Allo, Janet L. Williams, Marlene Z. Cohen
Journal: Journal of Clinical Oncology (2013)

Purpose Cancer-related-fatigue (CRF) is common in advanced cancer. The primary objective of the study was to compare the effects of methylphenidate (MP) with those of placebo (PL) on CRF as measured using the Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F) fatigue subscale. The effect of a combined intervention including MP plus a nursing telephone intervention (NTI) was also assessed. Patients and Methods Patients with advanced cancer with a fatigue score of ≥ 4 out of 10 on the Edmonton Symptom Assessment Scale (ESAS) were randomly assigned to one of the following four groups: MP+NTI, PL+NTI, MP + control telephone intervention (CTI), and PL+CTI. Methylphenidate dose was 5 mg every 2 hours as needed up to 20 mg per day. The primary end point was the median difference in FACIT-F fatigue at day 15. Secondary outcomes included anxiety, depression, and sleep. Results One hundred forty-one patients were evaluable. Median FACIT-F fatigue scores improved from baseline to day 15 in all groups: MP+NTI (median score, 4.5; P = .005), PL+NTI (median score, 8.0; P &lt; .001), MP+CTI (median score, 7.0; P = .004), and PL+CTI (median score, 5.0; P = .03). However, there were no significant differences in the median improvement in FACIT-F fatigue between the MP and PL groups (5.5 v 6.0, respectively; P = .69) and among all four groups (P = .16). Fatigue (P &lt; .001), nausea (P = .01), depression (P = .02), anxiety (P = .01), drowsiness (P &lt; .001), appetite (P = .009), sleep (P &lt; .001), and feeling of well-being (P &lt; .001), as measured by the ESAS, significantly improved in patients who received NTI. Grade ≥ 3 adverse events did not differ between MP and PL (40 of 93 patients v 29 of 97 patients, respectively; P = .06). Conclusion MP and NTI alone or combined were not superior to placebo in improving CRF.
Effect of cytomegalovirus immediate early gene products on endothelial cell gene activity
Authors: Esther Guetta, Eleonora M Scarpati, Paul E DiCorleto
Journal: Cardiovascular Research (2001)

Cytomegalovirus (CMV) infection or reactivation from latency in vascular cells have been shown to contribute to atherosclerosis. CMV-infected endothelial cells (ECs) exhibit enhanced adhesion and procoagulant properties, changes compatible with processes observed in atherogenesis. The major immediate early promoter drives immediate early gene transcription. Immediate early (IE) gene products, IE72 and IE84, function as transcription factors and thereby influence expression of cellular genes, in permissive cells as well as in abortive infections, in which viral activity is limited to immediate early expression. ECs have been shown to harbor latent CMV, support abortive CMV infection and, under certain conditions, are permissive to productive viral infection. The objective of this study was to determine whether immediate early expression alone (in the absence of further progression of the virus life-cycle) results in the activation of EC genes associated with atherogenesis.The study was conducted in an in vitro transient transfection system in human and bovine vascular ECs, with CMV immediate early gene expression vectors and plasmids containing promoter sequences of adhesion molecule, growth factor and viral promoters driving the transcription of reporter genes.CMV immediate early gene expression resulted in an increase in monocyte adhesion to ECs and in the relative promoter activities of cellular growth factor and adhesion molecule genes. In addition, the viral major immediate early promoter was regulated in EC by thrombin and the immediate early gene products.These results infer the possible existence of a positive feedback mechanism in the developing atherosclerotic lesion, in which enhanced immediate early gene expression leads to subsequent activation of EC genes, which might in turn result in further activation of CMV activity.
Decreased expression of ectonucleotidase E‐<scp>NPP</scp>1 in leukocytes from subjects with severe asthma exacerbation
Authors: L. M. Montaño, M. H. Vargas, V. Díaz‐Hernández, M. De Ita, R. Kazakova, C. Barajas‐López
Journal: Allergy (2015)

Several studies suggest that ATP and related nucleotides play a role in the pathophysiology of asthma. However, the functionality of ectonucleotidases in this disease has been scantly investigated. We studied total ectonucleotidase activity in leukocytes from patients suffering from asthma exacerbation and explored the expression of E-NTPDase 1, 2, 3, and 8, and E-NPP1, 2, and 3, in their polymorphonuclear cells by immunofluorescence and qPCR. Leukocytes from patients with mild or moderate asthma exacerbation had similar ectonucleotidase activity than leukocytes from healthy subjects, while in patients with severe asthma exacerbation, this activity was lower. Of the ectonucleotidases studied, only E-NPP1 displayed diminished immunofluorescence and a significant decrease in its mRNA expression, both in patients with severe asthma exacerbation. This reduced E-NPP1 expression could be responsible for increased amounts of ATP or other nucleotides, capable of worsening asthma exacerbation, and warranting further investigation.
Diabetic Foot Prevention
Authors: Lawrence A. Lavery, Nathan A. Hunt, Javier LaFontaine, Cory L. Baxter, Agbor Ndip, Andrew J.M. Boulton
Journal: Diabetes Care (2010)

OBJECTIVE To evaluate the frequency of foot prevention strategies among high-risk patients with diabetes. RESEARCH DESIGN AND METHODS Electronic medical records were used to identify 150 patients on dialysis and 150 patients with previous foot ulceration or amputation with 30 months follow-up to determine the frequency with which patients received education, podiatry care, and therapeutic shoes and insoles as prevention services. RESULTS Few patients had formal education (1.3%), therapeutic shoes/insoles (7%), or preventative podiatric care (30%). The ulcer incidence density was the same in both groups (210 per 1,000 person-years). In contrast, the amputation incidence density was higher in the dialysis group compared with the ulcer group (58.7 vs. 13.1 per 1,000 person-years, P &amp;lt; 0.001). Patients on dialysis were younger and more likely to be of non-Hispanic white descent (P = 0.006) than patients with a previous history of ulcer or amputation. CONCLUSIONS Prevention services are infrequently provided to high-risk patients.