tbuckley/cabot-search huggingface dataset:
Venlafaxine Extended-Release for Depression Following Spinal Cord Injury
Authors: Jesse R. Fann, Charles H. Bombardier, J. Scott Richards, Catherine S. Wilson, Allen W. Heinemann, Ann Marie Warren, Larry Brooks, Cheryl B. McCullumsmith, Nancy R. Temkin, Catherine Warms, Denise G. Tate
Journal: JAMA Psychiatry (2015)

Depression is prevalent and associated with negative outcomes in individuals with spinal cord injury (SCI). Antidepressants are used routinely to treat depression, yet no placebo-controlled trials have been published in this population to our knowledge.To determine the efficacy and tolerability of venlafaxine hydrochloride extended-release (XR) for major depressive disorder (MDD) or dysthymic disorder in persons with chronic SCI.Multisite, randomized (1:1), double-blind, placebo-controlled Project to Improve Symptoms and Mood After SCI (PRISMS) trial. All research staff conducting screening, intervention, and outcome procedures were blinded to randomization status. We screened 2536 patients from outpatient clinics at 6 SCI treatment centers in the United States and randomized 133 participants into the trial. Participants were 18 to 64 years old and at least 1 month after SCI, with MDD or dysthymic disorder. Seventy-four percent of participants were male, and participants were on average 40 years old and 11 years after SCI. Forty-seven percent had cervical injuries, 53.4% had American Spinal Injury Association injury severity A (complete injury) SCI, 24.1% had at least 2 prior MDD episodes, and 99.2% had current MDD. Common comorbidities included chronic pain (93.9%), significant anxiety (57.1%), and history of substance dependence (44.4%).Twelve-week trial of venlafaxine XR vs placebo using a flexible-dose algorithm.The Hamilton Depression Rating Scale (HAM-D 17-item version and Maier subscale, which focuses on core depression symptoms and excludes somatic symptoms) over 12 weeks.Mixed-effects models revealed a significant difference between the venlafaxine XR and placebo groups in improvement on the Maier subscale from baseline to 12 weeks (treatment effect, 1.6; 95% CI, 0.3-2.9; P = .02) but not on the HAM-D 17-item version (treatment effect, 1.0; 95% CI, -1.4 to 3.4; P = .42). Participants receiving venlafaxine XR reported significantly less SCI-related disability on the Sheehan Disability Scale at 12 weeks compared with placebo (treatment effect, 4.7; 95% CI, 1.5-7.8; P = .005). Blurred vision was the only significantly more common new or worsening adverse effect in the venlafaxine XR group compared with the placebo group over 12 weeks.Venlafaxine XR was well tolerated by most patients and an effective antidepressant for decreasing core symptoms of depression and improving SCI-related disability. Further research is needed to determine the optimal treatment and measurement approaches for depression in chronic SCI.clinicaltrials.gov Identifier: NCT00592384.
Inadequacy of Clinical Trial Designs and Data to Control for the Confounding Impact of Race/Ethnicity in Response to Treatment in Multiple Sclerosis
Authors: Jagannadha Avasarala
Journal: JAMA Neurology (2014)

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 Neurology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Neurology journal
Sphingosine-1-Phosphate Evokes Unique Segment-Specific Vasoconstriction of the Renal Microvasculature
Authors: Zhengrong Guan, Sean T. Singletary, Anthony K. Cook, Janet L. Hobbs, Jennifer S. Pollock, Edward W. Inscho
Journal: Journal of the American Society of Nephrology (2014)

Sphingosine-1-phosphate (S1P), a bioactive sphingolipid metabolite, has been implicated in regulating vascular tone and participating in chronic and acute kidney injury. However, little is known about the role of S1P in the renal microcirculation. Here, we directly assessed the vasoresponsiveness of preglomerular and postglomerular microvascular segments to exogenous S1P using the in vitro blood-perfused juxtamedullary nephron preparation. Superfusion of S1P (0.001-10 μM) evoked concentration-dependent vasoconstriction in preglomerular microvessels, predominantly afferent arterioles. After administration of 10 μM S1P, the diameter of afferent arterioles decreased to 35%±5% of the control diameter, whereas the diameters of interlobular and arcuate arteries declined to 50%±12% and 68%±6% of the control diameter, respectively. Notably, efferent arterioles did not respond to S1P. The S1P receptor agonists FTY720 and FTY720-phosphate and the specific S1P1 receptor agonist SEW2871 each evoked modest afferent arteriolar vasoconstriction. Conversely, S1P2 receptor inhibition with JTE-013 significantly attenuated S1P-mediated afferent arteriolar vasoconstriction. Moreover, blockade of L-type voltage-dependent calcium channels with diltiazem or nifedipine attenuated S1P-mediated vasoconstriction. Intravenous injection of S1P in anesthetized rats reduced renal blood flow dose dependently. Western blotting and immunofluorescence revealed S1P1 and S1P2 receptor expression in isolated preglomerular microvessels and microvascular smooth muscle cells. These data demonstrate that S1P evokes segmentally distinct preglomerular vasoconstriction via activation of S1P1 and/or S1P2 receptors, partially via L-type voltage-dependent calcium channels. Accordingly, S1P may have a novel function in regulating afferent arteriolar resistance under physiologic conditions.
Acute Exposure to Diesel Exhaust Increases IL-8 and GRO- α Production in Healthy Human Airways
Authors: SUNDEEP S. SALVI, CHARLOTTA NORDENHALL, ANDERS BLOMBERG, BERTIL RUDELL, JAMSHID POURAZAR, FRANK J. KELLY, SUSAN WILSON, THOMAS SANDSTRÖM, STEPHEN T. HOLGATE, ANTHONY J. FREW
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

We have previously demonstrated that short-term exposure to diesel exhaust (DE) for 1 h induced a marked leukocytic infiltration in the airways of healthy human volunteers involving neutrophils, lymphocytes, and mast cells along with increases in several inflammatory mediators. We hypothesized that the leukocyte infiltration and the various inflammatory responses induced by DE were mediated by enhanced chemokine and cytokine production by resident cells of the airway tissue and lumen. To investigate this, 15 healthy human volunteers were exposed to diluted DE and air on two separate occasions for 1 h each in an exposure chamber. Fiberoptic bronchoscopy was performed 6 h after each exposure to obtain endobronchial biopsies and bronchial wash (BW) cells. Using reverse transcriptase/polymerase chain reaction enzyme-linked immunosorbent assay (RT-PCR ELISA), a novel and sensitive technique to quantify relative amounts of cytokine mRNA gene transcripts, and immunohistochemical staining with computer-assisted image analysis to quantify expression of cytokine protein in the bronchial tissue, we have demonstrated that DE enhanced gene transcription of interleukin-8 (IL-8) in the bronchial tissue and BW cells along with increases in IL-8 and growth-regulated oncogene-alpha (GRO- α ) protein expression in the bronchial epithelium, and an accompanying trend toward an increase in IL-5 mRNA gene transcripts in the bronchial tissue. There were no significant changes in the gene transcript levels of interleukin-1B (IL-1 β ), tumor necrosis factor-alpha (TNF- α ), interferon gamma (IFN- γ ), and granulocyte macrophage colony–stimulating factor (GM-CSF) either in the bronchial tissue or BW cells after DE exposure at this time point. These observations suggest an underlying mechanism for DE-induced airway leukocyte infiltration and offer a possible explanation for the association observed between ambient levels of particulate matter and various respiratory health outcome indices noted in epidemiological studies. Salvi SS, Nordenhall C, Blomberg A, Rudell B, Pourazar J, Kelly FJ, Wilson S, Sandström T, Holgate ST, Frew AJ. Acute exposure to diesel exhaust increases IL-8 and GRO- α production in healthy human airways.
Targeting the mTOR/4E-BP Pathway in Endometrial Cancer
Authors: Sharmilee Bansal Korets, Sarah Czok, Stephanie V. Blank, John P. Curtin, Robert J. Schneider
Journal: Clinical Cancer Research (2011)

Endometrial cancer is the most common gynecologic malignancy. Although it is highly treatable in the early stages of disease, therapies for advanced and recurrent disease are rarely curative. A molecular and genetic understanding of endometrial cancer involves the mTOR signaling pathway, an emerging target for treatment of type I disease (the most common presentation). Endometrial cancers show a significant reliance on the mTOR pathway for survival, and studies to date have revealed a clinical advantage in targeting this pathway. Less well developed in the study of endometrial cancer is an understanding of mTOR signaling to its major downstream effector, translational control. Given the poor rate of success for treatment of late-stage endometrial cancer, increasing attention is being directed to the development of new therapeutic approaches, including targeting the mTOR pathway. Here, we discuss the potential benefit of targeting mTOR combined with existing chemotherapies by monitoring its impact on translational regulatory pathways and key translation targets in endometrial cancer. We also highlight laboratory and clinical research findings that will provide new avenues for future research and clinical development.
Antihypertensive drugs and the risk of incident rosacea
Authors: J. Spoendlin, J.J. Voegel, S.S. Jick, C.R. Meier
Journal: British Journal of Dermatology (2014)

Journal Article Antihypertensive drugs and the risk of incident rosacea Get access J. Spoendlin, J. Spoendlin Division of Clinical Pharmacy and Epidemiology Department of Pharmaceutical SciencesUniversity Hospital Basel Basel SwitzerlandBasel Pharmacoepidemiology Unit Hospital Pharmacy University Hospital Basel Basel Switzerland Search for other works by this author on: Oxford Academic Google Scholar J.J. Voegel, J.J. Voegel Galderma Research & Development Sophia Antipolis France Search for other works by this author on: Oxford Academic Google Scholar S.S. Jick, S.S. Jick Boston Collaborative Drug Surveillance Program Boston University Lexington MA U.S.A Search for other works by this author on: Oxford Academic Google Scholar C.R. Meier C.R. Meier Division of Clinical Pharmacy and Epidemiology Department of Pharmaceutical SciencesUniversity Hospital Basel Basel SwitzerlandBasel Pharmacoepidemiology Unit Hospital Pharmacy University Hospital Basel Basel SwitzerlandBoston Collaborative Drug Surveillance Program Boston University Lexington MA U.S.A Correspondence Christoph R. Meier. E‐mail: christoph.meier@usb.ch Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 171, Issue 1, 1 July 2014, Pages 130–136, https://doi.org/10.1111/bjd.12838 Published: 01 July 2014
Why do patients discontinue fertility treatment? A systematic review of reasons and predictors of discontinuation in fertility treatment
Authors: S. Gameiro, J. Boivin, L. Peronace, C.M. Verhaak
Journal: Human Reproduction Update (2012)

Chances of achieving parenthood are high for couples who undergo fertility treatment. However, many choose to discontinue before conceiving. A systematic review was conducted to investigate patients' stated reasons for and predictors of discontinuation at five fertility treatment stages. Six databases were systematically searched. Search-terms referred to fertility treatment and discontinuation. Studies reporting on patients' stated reasons for or predictors of treatment discontinuation were included. A list of all reasons for discontinuation presented in each study was made, different categories of reasons were defined and the percentage of selections of each category was calculated. For each predictor, it was noted how many studies investigated it and how many found a positive and/or negative association with discontinuation. The review included 22 studies that sampled 21 453 patients from eight countries. The most selected reasons for discontinuation were: postponement of treatment (39.18%, postponement of treatment or unknown 19.17%), physical and psychological burden (19.07%, psychological burden 14%, physical burden 6.32%), relational and personal problems (16.67%, personal reasons 9.27%, relational problems 8.83%), treatment rejection (13.23%) and organizational (11.68%) and clinic (7.71%) problems. Some reasons were common across stages (e.g. psychological burden). Others were stage-specific (e.g. treatment rejection during workup). None of the predictors reported were consistently associated with discontinuation. Much longitudinal and theory led research is required to explain discontinuation. Meanwhile, treatment burden should be addressed by better care organization and support for patients. Patients should be well informed, have the opportunity to discuss values and worries about treatment and receive advice to decide about continuing treatment.
Cellular and molecular aspects of contractile dysfunction in heart failure
Authors: C Mittmann
Journal: Cardiovascular Research (1998)

A number of molecular and cellular alterations have been identified in the failing human heart that help to understand contraction and relaxation abnormalities. Cyclic AMP dependent pathways are desensitized due to quantitative changes in beta-adrenoceptors, beta-adrenoceptor kinase, and inhibitory G-proteins. Calcium homeostasis is impaired, characterized by a decreased calcium reuptake rate of the sarcoplasmic reticulum, an increased threshold of the calcium release channel, and an increased Na+/Ca2+ exchanger expression. Myofibrillar function may be affected by a decrease in Mg2(+)-ATPase activity and in troponin I phosphorylation, and by changes in TnT isoform expression. These alterations seem to occur independently of the underlying etiology of heart failure and are most likely consequences rather than primary causes of the disease. Most likely, chronic neurohumoral activation and abnormal mechanical load initiate the majority of the hitherto known changes in the myocardium and promote the further progression of cardiac failure as part of a vicious circle. Further extension of knowledge of pathophysiological mechanisms should improve therapeutical strategies which aim at slowing the progression of heart failure and at reversing secondary alterations by interrupting the deleterious influence of neurohumoral activation. Future progress will depend on answers to current gaps in our knowledge of heart failure, including the unknown primary cause of idiopathic dilated cardiomyopathy, factors underlying the greatly variable progression of pump failure, as well as the exact pathophysiological role of the molecular alterations as described in this review.
Transient Receptor Potential Channel 6–Mediated, Localized Cytosolic [Na <sup>+</sup> ] Transients Drive Na <sup>+</sup> /Ca <sup>2+</sup> Exchanger–Mediated Ca <sup>2+</sup> Entry in Purinergically Stimulated Aorta Smooth Muscle Cells
Authors: Damon Poburko, Chiu-Hsiang Liao, Virginia S. Lemos, Eric Lin, Yoshiaki Maruyama, William C. Cole, Cornelis van Breemen
Journal: Circulation Research (2007)

The Na+/Ca2+ exchanger (NCX) is increasingly recognized as a physiological mediator of Ca2+ influx and significantly contributes to salt-sensitive hypertension. We recently reported that Ca2+ influx by the NCX (1) is the primary mechanism of Ca2+ entry in purinergically stimulated rat aorta smooth muscle cells and (2) requires functional coupling with transient receptor potential channel 6 nonselective cation channels. Using the Na+ indicator CoroNa Green, we now directly observed and characterized the localized cytosolic [Na+] ([Na+]i) elevations that have long been hypothesized to underlie physiological NCX reversal but that have never been directly shown. Stimulation of rat aorta smooth muscle cells caused both global and monotonic [Na+]i elevations and localized [Na+]i transients (LNats) at the cell periphery. Inhibition of nonselective cation channels with SKF-96365 (50 micromol/L) and 2-amino-4-phosphonobutyrate (75 micromol/L) reduced both global and localized [Na+]i elevations in response to ATP (1 mmol/L). This effect was mimicked by expression of a dominant negative construct of transient receptor potential channel 6. Selective inhibition of NCX-mediated Ca2+ entry with KB-R7943 (10 micromol/L) enhanced the LNats, whereas the global cytosolic [Na+] signal was unaffected. Inhibition of mitochondrial Na+ uptake with CGP-37157 (10 micromol/L) increased both LNats and global cytosolic [Na+] elevations. These findings directly demonstrate NCX regulation by LNats, which are restricted to subsarcolemmal, cytoplasmic microdomains. Analysis of the LNats, which facilitate Ca2+ entry via NCX, suggests that mitochondria limit the cytosolic diffusion of LNats generated by agonist-mediated activation of transient receptor potential channel 6-containing channels.
Anthranoid laxative abuse--a risk for colorectal cancer?
Authors: C P Siegers, E von Hertzberg-Lottin, M Otte, B Schneider
Journal: Gut (1993)

Anthranoid-containing laxatives--aloe, cascara, frangula, and rheum--may play a role in colorectal cancer. This risk is particularly important in view of the wide abuse of self administered laxatives for chronic constipation. There are data on the genotoxic potential of anthranoids and there is evidence of a tumourigenic potential in rodents. A case report and clinical-epidemiological studies have evaluated the cancer risk in patients who have abused anthranoid laxatives over a long period. Pseudomelanosis coli is a reliable parameter of chronic laxative abuse (> 9-12 months) and is specific for anthranoid drugs. In a retrospective study of 3049 patients who underwent diagnostic colorectal endoscopy the incidence of pseudomelanosis coli was 3.13% in patients without pathological changes. In those with colorectal adenomas, the incidence increased to 8.64% (p < 0.01), and in those with colorectal carcinomas it was 3.29%. This lower rate was probably caused by incomplete documentation of pseudomelanosis coli in those with carcinoma. In a prospective study of 1095 patients, the incidence of pseudomelanosis coli was 6.9% for patients with no abnormality seen on endoscopy, 9.8% (p = 0.068) for patients with adenomas, and 18.6% for patients with colorectal carcinomas. From these data a relative risk of 3.04 (1.18, 4.90; 95% confidence interval) can be calculated for colorectal cancer as a result of anthranoid laxative abuse.
ΔTAp73 Upregulation Correlates With Poor Prognosis in Human Tumors: Putative In Vivo Network Involving p73 Isoforms, p53, and E2F-1
Authors: Gemma Domínguez, José M. García, Cristina Peña, Javier Silva, Vanesa García, Lara Martínez, Constanza Maximiano, María E. Gómez, José A. Rivera, Carmen García-Andrade, Felix Bonilla
Journal: Journal of Clinical Oncology (2005)

Although full-length TAp73 variants largely mimic p53 suppressor activities, the transactivation-deficient transcripts DeltaTAp73 exert an oncogenic effect by inactivating p53 and TAp73 suppressor properties. Additionally, DeltaTAp73 may cooperate with oncogenic RAS to induce cell transformation, confer drug resistance, and induce the phosphorylation of phosphorylated Rb. Here, we study the expression of TAp73 and DeltaTAp73 variants and assess possible associations with E2F-1, p53 and K-ras status. We address the possible clinical relevance of alterations in these genes.We determine in 113 colon and 60 breast cancer patients (a) the expression levels of TAp73, DeltaTAp73 (DeltaEx2p73, DeltaEx2/3p73, and DeltaNp73), and E2F-1 transcripts by quantitative real-time reverse transcriptase polymerase chain reaction (PCR); (b) mutations in the first exon of K-ras by PCR-single-stranded confirmational polymorphism; and (c) p53 status by immunohistochemistry. Tumor characteristics were examined in each patient.Both suppressor and oncogenic isoforms of TP73 were significantly coupregulated in tumor tissues. Associations were observed between (a) p53 wild type status and upregulation of some TP73 variants; (b) overexpression of E2F-1 and some TP73 forms; and (c) upregulation of DeltaTAp73 variants and advanced pathologic stage, lymph node metastasis, vascular invasion, presence of polyps, and tumor localization.Overexpression of TP73 variants in tumor tissues indicates that they may be involved in colon and breast carcinogenesis. The association between upregulation of DeltaTAp73 isoforms and poor prognosis features, specifically advanced tumor stage, suggests that they may be of practical clinical prognostic value. Interestingly, the in vivo associations identified here may indicate a functional network involving p73 variants, p53, and E2F-1.
The acoustic reflection technique for non-invasive assessment of upper airway area
Authors: V Hoffstein, JJ Fredberg
Journal: European Respiratory Journal (1991)

Non-invasive assessment of upper airway area by acoustic reflections has been developed in the last 12 yrs. The technique is based on the analysis of sound waves reflected from the airways. Measurement of the amplitudes of the reflections and their times of arrival at the sensing microphone permits construction of a plot of airway area vs distance from the microphone. We describe the theoretical foundations of the method and review the underlying assumptions. This is followed by a summary of the results of in vitro and in vivo validation studies, with particular attention to the reproducibility, accuracy and variability of the technique. The description of clinical and physiological applications of this technique includes detection of tracheal stenosis, demonstration of structural and functional abnormalities of the pharynx and glottis in patients with sleep apnoea, dichotomous response of the airway area to exercise, and airway vs parenchymal hysteresis. Finally, we comment on the future directions that might be investigated using this technique.
1190 DANOPREVIR PLUS PEG-IFNa-2A/RIBAVIRIN FOR 12 WEEKS RESULTS IN DURABLE VIRAL SUPPRESSION AND LOW RATES OF RESISTANCE THROUGHOUT TREATMENT AND FOLLOW-UP: RESULTS FROM THE ATLAS STUDY
Authors: S. Le Pogam, M. Navarro, D.N. Thomas, K. Klumpp, I. Nájera
Journal: Journal of Hepatology (2012)