tbuckley/cabot-search huggingface dataset:
Nicotine Yield From Machine-Smoked Cigarettes and Nicotine Intakes in Smokers: Evidence From a Representative Population Survey
Authors: M J Jarvis, R Boreham, P Primatesta, C Feyerabend, A Bryant
Journal: JNCI Journal of the National Cancer Institute (2001)

The relevance of nicotine yields from machine-smoked cigarettes for quantifying smokers' nicotine intakes and exposure to cigarette toxins has been called into question. However, most studies of the relationship between nicotine yield and nicotine intake have been on relatively small and unrepresentative samples and have included few smokers of "ultra-low" brands (i.e., those yielding around 1 mg of tar and 0.1 mg of nicotine).We examined the relationship between salivary cotinine (a major metabolite of nicotine) concentrations and nicotine yields of machine-smoked cigarettes in a nationally representative sample of 2031 adult smokers of manufactured cigarettes surveyed in the 1998 Health Survey for England. We used standard linear regression techniques to examine associations and two-sided tests of statistical significance.Cotinine concentrations varied widely between smokers at any level of nominal brand nicotine yield. On average, cotinine levels were slightly lower in smokers of lower nicotine-yielding brands, but these smokers differed in terms of sex, socioeconomic profile, and cigarette consumption. After we controlled for potential confounders, nicotine yield from the brand smoked accounted for only 0.79% of the variation in saliva cotinine concentrations. Nicotine intake per cigarette smoked, as estimated from salivary cotinine level, did not correspond with machine-smoked yields at any level of nicotine yield. Nicotine intake per cigarette was about eight times greater than machine-smoked yields at the lowest deliveries (1.17 mg estimated nicotine intake per cigarette from brands averaging 0.14-mg delivery from machine smoking) and 1.4 times greater for the highest yield cigarettes (1.31-mg estimated nicotine intake per cigarette from brands averaging 0.91 mg from machine smoking).Smokers' tendency to regulate nicotine intake vitiates potential health gains from lower tar and nicotine cigarettes. Current approaches to characterizing tar and nicotine yields of cigarettes provide a simplistic guide to smokers' exposure that is misleading to consumers and regulators alike and should be abandoned.
Mortality and Poststroke Depression: A Placebo-Controlled Trial of Antidepressants
Authors: Ricardo E Jorge, Robert G Robinson, Stephan Arndt, Sergio Starkstein
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: Poststroke depression has been shown to increase mortality for more than 5 years after the stroke. The authors assessed whether antidepressant treatment would reduce poststroke mortality over 9 years of follow-up. METHOD: A total of 104 patients were randomly assigned to receive a 12-week double-blind course of nortriptyline, fluoxetine, or placebo early in the recovery period after a stroke. Mortality data were obtained for all 104 patients 9 years after initiation of the study. Demographic and clinical measurements were collected at 3, 6, 9, 12, 18, and 24 months after the stroke. Survival data were analyzed by using the Kaplan-Meier method. RESULTS: Of the 104 patients, 50 (48.1%) had died by the time of the 9-year follow-up. Of 53 patients who were given full-dose antidepressants, 36 (67.9%) were alive at follow-up, compared with only 10 (35.7%) of 28 placebo-treated patients, a significant difference. Logistic regression analysis showed that the beneficial effect of antidepressants remained significant both in patients who were depressed and in those who were nondepressed at enrollment, after the effects of other factors associated with mortality (i.e., age, coexisting diabetes mellitus, and chronic relapsing depression) were controlled. There were no intergroup differences in severity of stroke, impairment in cognitive functioning and activities of daily living impairment, and other medications received. CONCLUSIONS: Treatment with fluoxetine or nortriptyline for 12 weeks during the first 6 months poststroke significantly increased the survival of both depressed and nondepressed patients. This finding suggests that the pathophysiological processes determining the increased mortality risk associated with poststroke depression last longer than the depression itself and can be modified by antidepressants.
Screening for Familial Ovarian Cancer: Failure of Current Protocols to Detect Ovarian Cancer at an Early Stage According to the International Federation of Gynecology and Obstetrics System
Authors: Diane Stirling, D. Gareth R. Evans, Gabriella Pichert, Andrew Shenton, Elaine N. Kirk, Sylvia Rimmer, C. Michael Steel, Sheila Lawson, R.M. Camille Busby-Earle, Jane Walker, Fiona I. Lalloo, Diana M. Eccles, Anneke M. Lucassen, Mary E. Porteous
Journal: Journal of Clinical Oncology (2005)

To assess the effectiveness of annual ovarian cancer screening (transvaginal ultrasound and serum CA-125 estimation) in detecting presymptomatic ovarian cancer in women at increased genetic risk.A cohort of 1,110 women at increased risk of ovarian cancer were screened between January 1991 and March 2004; 553 were moderate-risk individuals (4% to 10% lifetime risk) and 557 were high-risk individuals (> 10% lifetime risk). Outcome measurements include the number and stage of screen-detected cancers, the number and stage of cancers not detected at screening, the number of equivocal screening results requiring recall/repetition, and the number of women undergoing surgery for benign disease.Thirteen epithelial ovarian malignancies (12 invasive and one borderline), developed in the cohort. Ten tumors were detected at screening: three International Federation of Gynecology and Obstetrics (FIGO) stage I (including borderline), two stage II, four stage III, and one stage IV. Of the three cancers not detected by screening, two were stage III and one was stage IV; 29 women underwent diagnostic surgery but were found not to have ovarian cancer.Annual surveillance by transvaginal ultrasound scanning and serum CA-125 measurement in women at increased familial risk of ovarian cancer is ineffective in detecting tumors at a sufficiently early stage to influence prognosis. With a positive predictive value of 17% and a sensitivity of less than 50%, the performance of ultrasound does not satisfy the WHO screening standards. In addition, the combined protocol has a particularly high false-positive rate in premenopausal women, leading to unnecessary surgical intervention.
Restoration of chemosensitivity for doxorubicin and cisplatin in chondrosarcoma in vitro: BCL-2 family members cause chemoresistance
Authors: J.G. van Oosterwijk, B. Herpers, D. Meijer, I.H. Briaire-de Bruijn, A.M. Cleton-Jansen, H. Gelderblom, B. van de Water, J.V.M.G. Bovée
Journal: Annals of Oncology (2011)
Histone Acetyltransferase PCAF Is Required for Hedgehog–Gli-Dependent Transcription and Cancer Cell Proliferation
Authors: Martina Malatesta, Cornelia Steinhauer, Faizaan Mohammad, Deo P. Pandey, Massimo Squatrito, Kristian Helin
Journal: Cancer Research (2013)

The Hedgehog (Hh) signaling pathway plays an important role in embryonic patterning and development of many tissues and organs as well as in maintaining and repairing mature tissues in adults. Uncontrolled activation of the Hh-Gli pathway has been implicated in developmental abnormalities as well as in several cancers, including brain tumors like medulloblastoma and glioblastoma. Inhibition of aberrant Hh-Gli signaling has, thus, emerged as an attractive approach for anticancer therapy; however, the mechanisms that mediate Hh-Gli signaling in vertebrates remain poorly understood. Here, we show that the histone acetyltransferase PCAF/KAT2B is an important factor of the Hh pathway. Specifically, we show that PCAF depletion impairs Hh activity and reduces expression of Hh target genes. Consequently, PCAF downregulation in medulloblastoma and glioblastoma cells leads to decreased proliferation and increased apoptosis. In addition, we found that PCAF interacts with GLI1, the downstream effector in the Hh-Gli pathway, and that PCAF or GLI1 loss reduces the levels of H3K9 acetylation on Hh target gene promoters. Finally, we observed that PCAF silencing reduces the tumor-forming potential of neural stem cells in vivo. In summary, our study identified the acetyltransferase PCAF as a positive cofactor of the Hh-Gli signaling pathway, leading us to propose PCAF as a candidate therapeutic target for the treatment of patients with medulloblastoma and glioblastoma.
Truth, Honesty, and the Therapeutic Process
Authors: LEON SALZMAN
Journal: American Journal of Psychiatry (1973)

The place of honesty and truthfulness in the therapeutic process has rarely been discussed in the psychiatric literature, although Freud placed great emphasis on the need for truthfulness. The author affirms the importance of absolute honesty by both therapist and patient, but cautions that the patient's ability to be honest may be limited by neurotic defenses and that the therapist must use discretion in sharing his honest appraisals with the patient. "Truth" is distinguished from honesty by the author, and its place in therapy is evaluated.
Effects of Eplerenone, Enalapril, and Eplerenone/Enalapril in Patients With Essential Hypertension and Left Ventricular Hypertrophy
Authors: Bertram Pitt, Nathaniel Reichek, Roland Willenbrock, Faiez Zannad, Robert A. Phillips, Barbara Roniker, Jay Kleiman, Scott Krause, Daniel Burns, Gordon H. Williams
Journal: Circulation (2003)

Background— Elevated renin-angiotensin-aldosterone system activity correlates with left ventricular hypertrophy (LVH) and cardiovascular risk, but the relative contributions of angiotensin II and aldosterone remain unclear. This study compared LVH regression during treatment with the selective aldosterone blocker eplerenone, enalapril, and their combination in patients with hypertension. Methods and Results— A 9-month, double-blind, randomized study was performed in 202 patients with LVH and hypertension who received eplerenone 200 mg daily, enalapril 40 mg daily, or eplerenone 200 mg and enalapril 10 mg daily. At week 8, hydrochlorothiazide 12.5 to 25 mg and/or amlodipine 10 mg was added if diastolic blood pressure was &gt;90 mm Hg. Change in left ventricular (LV) mass as assessed by MRI was the primary end point. Change in blood pressure, renin-angiotensin-aldosterone system hormones, albuminuria, and safety were also assessed. Eplerenone significantly reduced LV mass from baseline (−14.5±3.36 g; n=50) similarly to enalapril (−19.7±3.20 g; n=54; P =0.258), but eplerenone/enalapril (−27.2±3.39 g; n=49) was more effective than eplerenone alone ( P =0.007). All treatments reduced systolic blood pressure and diastolic blood pressure from baseline (eplerenone, −23.8 and −11.9 mm Hg; enalapril, −24.7 and −13.4 mm Hg; and eplerenone/enalapril, −28.7 and −14.4 mm Hg, P =0.048, in systolic blood pressure compared with eplerenone alone). Cough was more common with enalapril than with eplerenone ( P =0.033), and elevated potassium was more common with eplerenone. Conclusions— Eplerenone was as effective as enalapril in LVH regression and blood pressure control. The combination of eplerenone and enalapril was more effective in reducing LV mass and systolic blood pressure than eplerenone alone.
Prostanoid DP receptor polymorphisms may cause changes in susceptibility to asthma
Authors: C Prys-Picard
Journal: Thorax (2005)

▴ Oguma T, Palmer LJ, Birben E, et al . Role of prostanoid DP receptor variants in susceptibility to asthma. N Engl J Med2004;351:1752–63 [OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] Prostaglandins have been implicated in the pathophysiology of asthma. The prostaglandin receptor is expressed on the surface of airway eosinophils and mast cells. This group has studied the gene for the prostanoid DP receptor (PTGDR) and its relationship with the asthma phenotype. Screening revealed four new single nucleotide polymorphisms … [1]: {openurl}?query=rft.jtitle%253DNew%2BEngland%2BJournal%2Bof%2BMedicine%26rft.stitle%253DNEJM%26rft.issn%253D0028-4793%26rft.aulast%253DOguma%26rft.auinit1%253DT.%26rft.volume%253D351%26rft.issue%253D17%26rft.spage%253D1752%26rft.epage%253D1763%26rft.atitle%253DRole%2Bof%2BProstanoid%2BDP%2BReceptor%2BVariants%2Bin%2BSusceptibility%2Bto%2BAsthma%26rft_id%253Dinfo%253Adoi%252F10.1056%252FNEJMoa031785%26rft_id%253Dinfo%253Apmid%252F15496624%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1056/NEJMoa031785&link_type=DOI [3]: /lookup/external-ref?access_num=15496624&link_type=MED&atom=%2Fthoraxjnl%2F60%2F3%2F248.atom [4]: /lookup/external-ref?access_num=000224585200010&link_type=ISI
Hepatitis C virus infection: Molecular pathways to metabolic syndrome
Authors: Muhammad Y. Sheikh, Jinah Choi, Ishtiaq Qadri, Jacob E. Friedman, Arun J. Sanyal
Journal: Hepatology (2008)

Chronic infection with hepatitis C virus (HCV) can induce insulin resistance (IR) in a genotype-dependent fashion, thus contributing to steatosis, progression of fibrosis and resistance to interferon therapy. The molecular mechanisms in genotype 1 patients that lead to metabolic syndrome are still ambiguous. Based on our current understanding, HCV proteins associate with mitochondria and endoplasmic reticulum and promote oxidative stress. The latter mediates signals involving the p38 mitogen-activated protein kinase and activates nuclear factor kappa B. This transcription factor plays a key role in the expression of cytokines, tumor necrosis factor alpha (TNF-α), interleukin 6, interleukin 8, tumor growth factor beta, and Fas ligand. TNF-α inhibits the function of insulin receptor substrates and decreases the expression of the glucose transporter and lipoprotein lipase in peripheral tissues, which is responsible for the promotion of insulin resistance. Furthermore, reduced adiponectin levels, loss of adiponectin receptors, and decreased anti-inflammatory peroxisome proliferator-activated receptor alpha in the liver of HCV patients may contribute to reduced fatty acid oxidation, inflammation, and eventually lipotoxicity. This chain of events may be initiated by HCV-associated IR and provides a direction for future research in the areas of therapeutic intervention.
Leptin secretion and leptin receptor in the human stomach
Authors: I Sobhani
Journal: Gut (2000)

<h3>BACKGROUND AND AIM</h3> The circulating peptide leptin produced by fat cells acts on central receptors to control food intake and body weight homeostasis. Contrary to initial reports, leptin expression has also been detected in the human placenta, muscles, and recently, in rat gastric chief cells. Here we investigate the possible presence of leptin and leptin receptor in the human stomach. <h3>METHODS</h3> Leptin and leptin receptor expression were assessed by immunohistochemistry, reverse transcriptase-polymerase chain reaction (RT-PCR), and western blot analysis on biopsy samples from 24 normal individuals. Fourteen (10 healthy volunteers and four patients with non-ulcer dyspepsia and normal gastric mucosa histology) were analysed for gastric secretions. Plasma and fundic mucosa leptin content was determined by radioimmunoassay. <h3>RESULTS</h3> In fundic biopsies from normal individuals, immunoreactive leptin cells were found in the lower half of the fundic glands. mRNA encoding ob protein was detected in the corpus of the human stomach. The amount of fundic leptin was 10.4 (3.7) ng leptin/g mucosa, as determined by radioimmunoassay. Intravenous infusions of pentagastrin or secretin caused an increase in circulating leptin levels and leptin release into the gastric juice. The leptin receptor was present in the basolateral membranes of fundic and antral gastric cells. mRNA encoding Ob-RL was detected in both the corpus and antrum, consistent with a protein of ∼120 kDa detected by immunoblotting. <h3>CONCLUSION</h3> These data provide the first evidence of the presence of leptin and leptin receptor proteins in the human stomach and suggest that gastric epithelial cells may be direct targets for leptin. Therefore, we conclude that leptin may have a physiological role in the human stomach, although much work is required to establish this.
Modulation of Breast Cancer Risk by Nonsteroidal Anti-inflammatory Drugs
Authors: L. R. Howe, S. M. Lippman
Journal: JNCI Journal of the National Cancer Institute (2008)

their fi ndings on NSAID use and breast cancer risk?The answer lies in an appreciation of the likely mechanisms of NSAIDmediated breast cancer suppression.COX enzymes, the primary molecular targets of NSAIDs, synthesize prostaglandins (PGs) from arachidonic acid ( 13 , 14 ).COX-1 is normally expressed constitutively, whereas COX-2 is an earlyresponse gene whose expression is increased in response to growth factors, oncogenes, and cytokines and is a key component of the infl ammatory response ( 5 , 14 , 15 ).Transgenic overexpression of COX-2 induces mammary tumor formation in mice ( 16 ); activation of COX/PG signaling has multiple procarcinogenic consequences, including regulation of proliferation, apoptosis, angiogenesis, invasion, and immune responsiveness ( 5 , 14 ).Patterns of COX-2 overexpression differ substantially between breast and colorectal neoplasia.Nonsteroidal anti-inflammatory drugs (NSAIDs) clearly reduce the risk of human colorectal neoplasia in epidemiological and prospective randomized clinical studies of aspirin and nonaspirin NSAIDs, including selective cyclooxygenase-2 (COX-2) inhibitors, or coxibs ( 1 -3 ).In contrast, the epidemiological and clinical data on NSAIDs in reducing breast cancer risk are not consistent.This inconsistency is likely attributable to contrasting expression patterns of COX-2, a key target of NSAIDs, in breast and colon neoplasia ( 4 , 5 ), and to differing activities of individual NSAIDs (which have varying selectivity for COX-2 vs COX-1), including a potentially selective impact of certain NSAIDs on hormone receptor -positive breast tumors.In this issue of the Journal, Takkouche et al. ( 6) report an extensive meta-analysis (involving 38 studies) supporting an inverse association between NSAID use and risk of breast cancer .They found a statistically signifi cant reduction in breast cancer risk associated with use of any NSAID (relative risk [RR] = 0.88, 95% confi dence interval [CI] = 0.84 to 0.93) and similar associations for aspirin (RR = 0.87, 95% CI = 0.82 to 0.92) and ibuprofen (RR = 0.79, 95% CI = 0.64 to 0.97).They found no evidence of a doseresponse relationship, and some studies indicated that coxibs were also associated with a lower risk of breast cancer ( 7 , 8 ).This large-scale meta-analysis is consistent with several smaller meta-analyses ( 9 -12 ).Furthermore, NSAIDs can prevent experimental breast cancer in numerous rodent models ( 4 , 5 ).Why then do individual observational and clinical studies vary substantially in
Points: Hospital doctors' responsibility for prescribing
Authors: S E Josse
Journal: BMJ (1987)

Dr Norman D Noah (16 May, p 1270) rightly draws attention to the comparatively limited information available on compulsory childhood immunisation and its impact in eastern European countries.He specifically mentions Czechoslovakia, a country which I recently visited as a medical geographer with a specific interest in vaccination uptake and the epidemiology of infectious disease.In Czechoslovakia virtual eradication ofmeasles seems to have been attained by a combination of compulsory childhood immunisation and the measures which Dr Noah commends: administrative methods, health education, and service delivery.Though immunisa-
Effects of corticosteroid treatment on pulmonary haemodynamics in patients with sarcoidosis
Authors: J Gluskowski, I Hawrylkiewicz, D Zych, J Zielinski
Journal: European Respiratory Journal (1990)

Effects of 12 months steroid treatment on pulmonary haemodynamics in 24 patients with pulmonary sarcoidosis, stage II and III, were investigated. All patients had a chest radiograph, lung function tests, and pulmonary haemodynamics (measured at rest and during submaximal exercise) prior to the treatment. Resting pulmonary hypertension was found in 3 patients. In 18 an abnormal increase in pulmonary arterial mean pressure (PAP) on exercise was observed. All investigations were repeated after a year of treatment. In almost all patients (22) a regression of radiological changes in the lungs and improvement of pulmonary function were observed. The changes in pulmonary circulation were less uniform. In only half of the patients studied was regression of the disease seen on chest X-ray and improvement in lung function accompanied by improvement in pulmonary haemodynamics.
Impact of Diabetes Among Revascularized Patients in Japan and the U.S.
Authors: Shun Kohsaka, Masashi Goto, Toshiyuki Nagai, Vei-Vei Lee, MacArthur Elayda, Yutaka Furukawa, Masanori Fukushima, Masashi Komeda, Ryuzo Sakata, Mitsuru Ohsugi, Keiichi Fukuda, James M. Wilson, Toru Kita, Takeshi Kimura
Journal: Diabetes Care (2012)

Approximately 25% of patients who undergo percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) have diabetes, and the diagnosis of diabetes roughly doubles the mortality risk associated with coronary artery disease. However, the impact of diabetes may differ according to ethnicity. Our objective was to examine the impact of diabetes on long-term survival among U.S. and Japanese patients who underwent PCI or CABG.For the current analysis, we included 8,871 patients from a Japanese multicenter registry (Coronary Revascularization Demonstrating Outcome database in Kyoto; median follow-up 3.5 years; interquartile range [IQR] 2.6-4.3) and 7,229 patients from a U.S. multipractice registry (Texas Heart Institute Research Database; median follow-up 5.2 years; IQR 3.8-6.5).Diabetes was more prevalent among Japanese than U.S. patients (39.2 vs. 31.0%; P < 0.001). However, after revascularization, long-term all-cause mortality was lower in diabetic Japanese patients than in diabetic U.S. patients (85.4 vs. 82.2%; log-rank test P = 0.009), whereas it was similar in nondiabetic Japanese and U.S. patients (89.1 vs. 89.5%; P = 0.50). The national difference in crude mortality was also significant among insulin-using patients with diabetes (80.8 vs. 74.9%; P = 0.023). When long-term mortality was adjusted for known predictors, U.S. location was associated with greater long-term mortality risk than Japanese location among nondiabetic patients (hazard ratio 1.58 [95% CI 1.32-1.88]; P < 0.001) and, especially, diabetic patients (1.88 [1.54-2.30]; P < 0.001).Although diabetes was less prevalent in U.S. patients than in Japanese patients, U.S. patients had higher overall long-term mortality risk. This difference was more pronounced in diabetic patients.