tbuckley/cabot-search huggingface dataset:
Roxithromycin Treatment Prevents Progression of Peripheral Arterial Occlusive Disease in <b> <i>Chlamydia pneumoniae</i> </b> Seropositive Men
Authors: Peter Wiesli, Wolfgang Czerwenka, Alfredo Meniconi, Friedrich E. Maly, Ulrich Hoffmann, Wilhelm Vetter, Georg Schulthess
Journal: Circulation (2002)

Background — Evidence has been provided that the atherosclerotic process may be associated with chronic infection with Chlamydia pneumoniae . The effect of antibiotic treatment on peripheral arterial occlusive disease has not been investigated yet. Methods and Results — Forty C pneumoniae seropositive men suffering from peripheral arterial occlusive disease were randomly assigned to receive either roxithromycin (300 mg daily) or placebo for 28 days. During the 2.7-year follow-up, the number of invasive revascularizations per patient, the walking distance before intervention (in patients without intervention at study end), and the change of carotid plaque size were assessed. Five interventions were performed on 4 patients (20%) in the roxithromycin group, and 29 interventions were performed on 9 patients (45%) in the placebo group. Limitation of walking distance to 200 m or less was observed in 4 patients (20%) in the roxithromycin group and in 13 patients (65%) in the placebo group. The effect of macrolide treatment on the number of interventions per patient and on preinterventional walking distance was significant. Possible confounding variables such as classical vascular risk factors were excluded by multiple regression analyses. Carotid plaque areas monitored over 6 months decreased in the roxithromycin group (mean relative value, 94.4%) but remained constant in the placebo group (100.2%). Regression of carotid plaque size observed in roxithromycin-treated patients was significant for soft plaques. Conclusions — This study indicates that macrolide treatment for 1 month is effective in preventing C pneumoniae seropositive men from progression of lower limb atherosclerosis for several years.
Diabetes, Inflammation, and Functional Decline in Older Adults
Authors: M. Kathleen Figaro, Stephen B. Kritchevsky, Helaine E. Resnick, Ronald I. Shorr, Javed Butler, Ayumi Shintani, Brenda W. Penninx, Eleanor M. Simonsick, Bret H. Goodpaster, Anne B. Newman, Ann V. Schwartz, Tamara B. Harris
Journal: Diabetes Care (2006)

Age, diabetes, and elevated inflammatory markers independently increase the risk of functional decline. We examined the effect of C-reactive protein (CRP) and interleukin-6 (IL-6) on the incident mobility limitation in older adults with and without diabetes.We analyzed data from a cohort of 2,895 well-functioning adults aged 70-79 years, followed for development of persistent functional limitation over 3.5 years. Participants were assessed for the presence of diabetes according to fasting glucose and/or hypoglycemic medication use and were divided into three equal groups (tertiles) according to level of CRP or IL-6. Persistent functional limitation was defined as difficulty climbing 10 steps or walking one-quarter mile on two consecutive semiannual assessments.At baseline, 702 participants (24%) had diabetes. CRP values were (median +/- SD) 2.8 +/- 4.4 versus 3.7 +/- 5.4 for those with normal glucose and diabetes, respectively (P < 0.001). The unadjusted incidence of functional limitation associated with increased levels of CRP and IL-6 was greater among participants with diabetes. After adjusting for clinical and demographic covariates, persistent functional limitation for the highest tertile was greater compared with that for the lowest tertile of CRP or IL-6 for those with and without diabetes. CRP hazard ratios (HRs) were 1.7 (95% CI 1.2-2.3) versus 1.4 (1.1-1.6), respectively. IL-6 HRs were 1.8 (1.3-2.5) versus 1.6 (1.4-2.0), respectively.In initially high-functioning older adults, those with diabetes and higher inflammatory burden had an increased risk of functional decline. Interventions at early stages to reduce inflammation may preserve function in these individuals.
Microstructural White Matter Abnormalities and Remission of Geriatric Depression
Authors: George S. Alexopoulos, Christopher F. Murphy, Faith M. Gunning-Dixon, Vassilios Latoussakis, Dora Kanellopoulos, Sibel Klimstra, Kelvin O. Lim, Matthew J. Hoptman
Journal: American Journal of Psychiatry (2008)

Objective: White matter abnormalities may interfere with limbic cortical balance and lead to chronic depressive syndromes. The authors used diffusion tensor imaging to test the hypothesis that depressed elders who fail to achieve remission have microstructural white matter abnormalities in cortico-striato-limbic networks implicated in geriatric depression. Method: The subjects were nondemented individuals with nonpsychotic major depression. After a 2-week placebo period, those subjects who had a Hamilton Depression Rating Scale (HAM-D) score of 18 or greater received escitalopram, 10 mg daily, for 12 weeks. Remission was defined as a HAM-D score of 7 or below for 2 consecutive weeks. Diffusion tensor imaging was performed at a 1.5 Tesla scanner, and voxel-based analysis of fractional anisotropy was conducted using age as the covariate. Results: Subjects who failed to achieve remission (N=23) had lower fractional anisotropy in multiple frontal limbic brain areas, including the rostral and dorsal anterior cingulate, dorsolateral prefrontal cortex, genu of the corpus callosum, white matter adjacent to the hippocampus, multiple posterior cingulate cortex regions, and insular white matter, relative to those who achieved remission (N=25). In addition, lower fractional anisotropy was detected in the neostriatum and midbrain as well as select temporal and parietal regions. Conclusions: Lower fractional anisotropy in distributed cerebral networks is associated with poor antidepressant response of geriatric depression and may represent a neuroanatomical substrate that predisposes to this disorder.
BLM Helicase Facilitates Mus81 Endonuclease Activity in Human Cells
Authors: Ran Zhang, Sagar Sengupta, Qin Yang, Steven P. Linke, Nozomu Yanaihara, John Bradsher, Veronique Blais, Clare H. McGowan, Curtis C. Harris
Journal: Cancer Research (2005)

Bloom syndrome is a rare, autosomal recessive inherited disorder in humans. The product of the Bloom syndrome mutated gene, designated BLM, is a member of the RecQ helicase family. BLM has been proposed to function at the interface of replication and recombination, and to facilitate the repair of DNA damage. Here, we report in vivo physical interaction and colocalization of BLM and a DNA structure-specific endonuclease, Mus81, at sites of stalled replication forks outside the promyelocytic leukemia nuclear bodies during the S-phase arrest of the cell cycle. Amino acids 125 to 244 of Mus81 interact with the C-terminal region (amino acids 1,007-1,417) of BLM. Whereas Mus81 does not have any effect on the helicase activity of BLM, BLM can stimulate Mus81 endonuclease activity on the nicked Holliday junctions and 3' flap. This stimulation is due to enhanced binding of Mus81 to the DNA substrates. These data suggest a new function of BLM in cooperating with Mus81 during processing and restoration of stalled replication forks.
Standards for Therapeutic Trials
Authors: D. H. Spodick, W. Aronow, B. Lown, B. Barber, V. S. Mathur, Henry Blackburn, H. D. McIntosh, D. Boyd, T. A. Preston, C. R. Conti, A. Selzer, J. P. LoGerfo, T. Takaro
Journal: Annals of Internal Medicine (1978)

Letters and Corrections1 September 1978Standards for Therapeutic TrialsDAVID H. SPODICK, M.D., D.SC., WILBERT ARONOW, M.D., BERNARD LOWN, M.D., BERNARD BARBER, PH.D., VIRENDRA S. MATHUR, M.D., HENRY BLACKBURN, M.D., HENRY D. MCINTOSH, M.D., DAVID BOYD, M.D., THOMAS A. PRESTON, M.D., C. RICHARD CONTI, M.D., ARTHUR SELZER, M.D., JAMES P. LOGERFO, M.D., TIMOTHY TAKARO, M.D.DAVID H. SPODICK, M.D., D.SC.Search for more papers by this author, WILBERT ARONOW, M.D.Search for more papers by this author, BERNARD LOWN, M.D.Search for more papers by this author, BERNARD BARBER, PH.D.Search for more papers by this author, VIRENDRA S. MATHUR, M.D.Search for more papers by this author, HENRY BLACKBURN, M.D.Search for more papers by this author, HENRY D. MCINTOSH, M.D.Search for more papers by this author, DAVID BOYD, M.D.Search for more papers by this author, THOMAS A. PRESTON, M.D.Search for more papers by this author, C. RICHARD CONTI, M.D.Search for more papers by this author, ARTHUR SELZER, M.D.Search for more papers by this author, JAMES P. LOGERFO, M.D.Search for more papers by this author, TIMOTHY TAKARO, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-89-3-422_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In theory, reviewers of scientific papers impose standards for acceptance based on the aim of all scientists—to report a true result. For therapeutic trials, a true result depends on appropriate design, that is, the results should reveal real treatment effects by measures that minimize biases in selecting patients and administering therapy. Acceptance of the results for publication implies merit, and without publication it is very difficult to establish a new treatment in practice. Medical journals thus become the filter through which appropriately studied modalities can go on to application but through which inappropriately studied modalities should not... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: DAVID H. SPODICK, M.D., D.SC.; WILBERT ARONOW, M.D.; BERNARD LOWN, M.D.; BERNARD BARBER, PH.D.; VIRENDRA S. MATHUR, M.D.; HENRY BLACKBURN, M.D.; HENRY D. MCINTOSH, M.D.; DAVID BOYD, M.D.; THOMAS A. PRESTON, M.D.; C. RICHARD CONTI, M.D.; ARTHUR SELZER, M.D.; JAMES P. LOGERFO, M.D.; TIMOTHY TAKARO, M.D.Affiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 September 1978Volume 89, Issue 3Page: 422-422 ePublished: 1 December 2008 Issue Published: 1 September 1978 PDF downloadLoading ...
Risks of Primary Extracolonic Cancers Following Colorectal Cancer in Lynch Syndrome
Authors: A. K. Win, N. M. Lindor, J. P. Young, F. A. Macrae, G. P. Young, E. Williamson, S. Parry, J. Goldblatt, L. Lipton, I. Winship, B. Leggett, K. M. Tucker, G. G. Giles, D. D. Buchanan, M. Clendenning, C. Rosty, J. Arnold, A. J. Levine, R. W. Haile, S. Gallinger, L. L. Marchand, P. A. Newcomb, J. L. Hopper, M. A. Jenkins
Journal: JNCI Journal of the National Cancer Institute (2012)

Lynch syndrome is a highly penetrant cancer predisposition syndrome caused by germline mutations in DNA mismatch repair (MMR) genes. We estimated the risks of primary cancers other than colorectal cancer following a diagnosis of colorectal cancer in mutation carriers. We obtained data from the Colon Cancer Family Registry for 764 carriers of an MMR gene mutation (316 MLH1, 357 MSH2, 49 MSH6, and 42 PMS2), who had a previous diagnosis of colorectal cancer. The Kaplan–Meier method was used to estimate their cumulative risk of cancers 10 and 20 years after colorectal cancer. We estimated the age-, sex-, country- and calendar period–specific standardized incidence ratios (SIRs) of cancers following colorectal cancer, compared with the general population. Following colorectal cancer, carriers of MMR gene mutations had the following 10-year risk of cancers in other organs: kidney, renal pelvis, ureter, and bladder (2%, 95% confidence interval [CI] = 1% to 3%); small intestine, stomach, and hepatobiliary tract (1%, 95% CI = 0.2% to 2%); prostate (3%, 95% CI = 1% to 5%); endometrium (12%, 95% CI = 8% to 17%); breast (2%, 95% CI = 1% to 4%); and ovary (1%, 95% CI = 0% to 2%). They were at elevated risk compared with the general population: cancers of the kidney, renal pelvis, and ureter (SIR = 12.54, 95% CI = 7.97 to 17.94), urinary bladder (SIR = 7.22, 95% CI = 4.08 to 10.99), small intestine (SIR = 72.68, 95% CI = 39.95 to 111.29), stomach (SIR = 5.65, 95% CI = 2.32 to 9.69), and hepatobiliary tract (SIR = 5.94, 95% CI = 1.81 to 10.94) for both sexes; cancer of the prostate (SIR = 2.05, 95% CI = 1.23 to 3.01), endometrium (SIR = 40.23, 95% CI = 27.91 to 56.06), breast (SIR = 1.76, 95% CI = 1.07 to 2.59), and ovary (SIR = 4.19, 95% CI = 1.28 to 7.97). Carriers of MMR gene mutations who have already had a colorectal cancer are at increased risk of a greater range of cancers than the recognized spectrum of Lynch syndrome cancers, including breast and prostate cancers.
Role of a Plasminogen Activator Inhibitor-1 4G/5G polymorphism in the development and clinical outcome of Idiopathic Sudden Sensorineural Hearing Loss
Authors: J. Kim, H. Chen, I. Kim, C. Yokose, C. Cai, S. Palma, M. Busi, A. Martini, T.J. Yoo, S.H. Cho
Journal: Journal of Allergy and Clinical Immunology (2012)
Comparison of static and dynamic measurements of intrinsic PEEP in mechanically ventilated patients.
Authors: F Maltais, H Reissmann, P Navalesi, P Hernandez, A Gursahaney, V M Ranieri, M Sovilj, S B Gottfried
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Intrinsic positive end-expiratory pressure (PEEPi) is routinely determined under static conditions by occluding the airway at end-expiration (PEEPi,stat), the resulting plateau pressure representing the average PEEPi present within a nonhomogeneous lung. In contrast, PEEPi can also be evaluated dynamically (PEEPi,dyn) by recording the change in pressure required to initiate lung inflation. It has been suggested that PEEPi,dyn reflects the lowest regional PEEPi, and therefore underestimates PEEPi,stat in the presence of heterogenous mechanical properties. The purposes of this study were (1) to compare PEEPi obtained with these two methods in mechanically ventilated patients with significant airway obstruction (AWO) and those without (non-AWO), and (2) to relate any discrepancies observed with other indices of respiratory mechanics. PEEPi,stat, PEEPi,dyn, and respiratory mechanics were measured during controlled mechanical ventilation in 22 sedated, paralyzed patients. PEEPi,dyn was significantly less than PEEPi,stat in AWO, averaging 3.0 +/- 0.5 (SEM) and 9.3 +/- 1.1 (SEM) cm H2O, respectively (p < 0.0001). In contrast, these values were more comparable in non-AWO, averaging 4.6 +/- 0.8 and 5.4 +/- 1.0 cm H2O (p > 0.05). As a result, the ratio of PEEPi,dyn to PEEPi,stat amounted to 0.36 +/- 0.06 for AWO compared with 0.87 +/- 0.05 in non-AWO (p < 0.005). Maximal (Rmax) and minimal (Rmin) respiratory resistance were greater in AWO whereas respiratory compliance (Crs) was no different between groups. PEEPi,dyn/PEEPi,stat was inversely related to delta P, the pressure losses attributable to time constant inequalities and viscoelastic tissue properties (r = 0.64, p < 0.005). No correlation was found between this ratio and Rmax, Rmin, or Crs.(ABSTRACT TRUNCATED AT 250 WORDS)
Fatty Acid Synthase Inhibition Activates AMP-Activated Protein Kinase in SKOV3 Human Ovarian Cancer Cells
Authors: Weibo Zhou, Wan Fang Han, Leslie E. Landree, Jagan N. Thupari, Michael L. Pinn, Tsion Bililign, Eun Kyoung Kim, Aravinda Vadlamudi, Susan M. Medghalchi, Rajaa El Meskini, Gabriele V. Ronnett, Craig A. Townsend, Francis P. Kuhajda
Journal: Cancer Research (2007)

Abstract Fatty acid synthase (FAS), the enzyme responsible for the de novo synthesis of fatty acids, is highly expressed in ovarian cancers and most common human carcinomas. Inhibition of FAS and activation of AMP-activated protein kinase (AMPK) have been shown to be cytotoxic to human cancer cells in vitro and in vivo. In this report, we explore the cytotoxic mechanism of action of FAS inhibition and show that C93, a synthetic FAS inhibitor, increases the AMP/ATP ratio, activating AMPK in SKOV3 human ovarian cancer cells, which leads to cytotoxicity. As a physiologic consequence of AMPK activation, acetyl-CoA carboxylase (ACC), the rate-limiting enzyme of fatty acid synthesis, was phosphorylated and inhibited whereas glucose oxidation was increased. Despite these attempts to conserve energy, the AMP/ATP ratio increased with worsening cellular redox status. Pretreatment of SKOV3 cells with compound C, an AMPK inhibitor, substantially rescued the cells from C93 cytotoxicity, indicating its dependence on AMPK activation. 5-(Tetradecyloxy)-2-furoic acid, an ACC inhibitor, did not activate AMPK despite inhibiting fatty acid synthesis pathway activity and was not significantly cytotoxic to SKOV3 cells. This indicates that substrate accumulation from FAS inhibition triggering AMPK activation, not end-product depletion of fatty acids, is likely responsible for AMPK activation. C93 also exhibited significant antitumor activity and apoptosis against SKOV3 xenografts in athymic mice without significant weight loss or cytotoxicity to proliferating cellular compartments such as bone marrow, gastrointestinal tract, or skin. Thus, pharmacologic FAS inhibition selectively activates AMPK in ovarian cancer cells, inducing cytotoxicity while sparing most normal human tissues from the pleiotropic effects of AMPK activation. [Cancer Res 2007;67(7):2964–71]
Forensic Experts and Disasters
Authors: E. T. McDonough
Journal: JAMA (1985)

<h3>To the Editor.—</h3> Ms Glasbrenner<sup>1</sup>reported on the need for disaster planning to utilize resources more efficiently and save as many lives as possible. She stressed that a disaster, natural or man-made, is a time for community action. Physicians as individuals and as a group must interact with all other community services (police, fire, ambulance, and government) on a scale that would never be equaled on a day-to-day basis in an emergency room. However, one critical aspect of the physician-community plan was not alluded to. We believe that the participation of the forensic medicine specialists is critical. The local or state medical examiners' offices should be an integral part of the disaster response team because it is a rare disaster that does not include fatalities. The medical examiners and their forensic teams are needed at several levels. One, and the most immediate, is the need to identify correctly the
Combined loss of orphan receptors PXR and CAR heightens sensitivity to toxic bile acids in mice
Authors: Hirdesh Uppal, David Toma, Simrat P.S. Saini, Songrong Ren, Thomas J. Jones, Wen Xie
Journal: Hepatology (2005)

Efficient detoxification of bile acids is necessary to avoid pathological conditions such as cholestatic liver damage and colon cancer. The orphan nuclear receptors PXR and CAR have been proposed to play an important role in the detoxification of xeno- and endo-biotics by regulating the expression of detoxifying enzymes and transporters. In this report, we showed that the combined loss of PXR and CAR resulted in a significantly heightened sensitivity to bile acid toxicity in a sex-sensitive manner. A regimen of lithocholic acid treatment, which was tolerated by wild-type and PXR null mice, caused a marked accumulation of serum bile acids and histological liver damage as well as an increased hepatic lipid deposition in double knockout males. The increased sensitivity in males was associated with genotype-specific suppression of bile acid transporters and loss of bile acid-mediated downregulation of small heterodimer partner, whereas the transporter suppression was modest or absent in females. The double knockout mice also exhibited gene- and tissue-specific dysregulation of PXR and CAR target genes in response to PXR and CAR agonists. In conclusion, althoughthe cross-regulation of target genes by PXR and CAR has b een proposed, the current study represents in vivo evidence of the combined loss of both receptors causing a unique pattern of gene regulation that can be translated into physiological events such as sensitivity to toxic bile acids.
Colorectal Tumors Are Effectively Eradicated by Combined Inhibition of β-Catenin, KRAS, and the Oncogenic Transcription Factor ITF2
Authors: Luca Mologni, Hafedh Dekhil, Monica Ceccon, Stefania Purgante, Cathy Lan, Loredana Cleris, Vera Magistroni, Franca Formelli, Carlo B. Gambacorti-Passerini
Journal: Cancer Research (2010)

Colorectal carcinomas (CRC) harbor well-defined genetic abnormalities, including aberrant activation of β-catenin (β-cat) and KRAS, but independent targeting of these molecules seems to have limited therapeutic effect. In this study, we report therapeutic effects of combined targeting of different oncogenes in CRC. Inducible short hairpin RNA (shRNA)-mediated silencing of β-cat, ITF2, or KRAS decreased proliferation by 88%, 72%, and 45%, respectively, with no significant apoptosis in any case. In contrast, combined blockade of β-cat and ITF2 inhibited proliferation by 99% with massive apoptosis. Similar effects occurred after combined shRNA against β-cat and KRAS. In vivo, single oncogene blockade inhibited the growth of established tumors by up to 30%, whereas dual β-cat and ITF2 targeting caused 93% inhibition. Similar tumor growth suppression was achieved by double β-cat/KRAS shRNA in vivo. Our findings illustrate an effective therapeutic principle in CRC based on a combination targeting strategy that includes the ITF2 oncogene, which represents a novel therapeutic target.
Oxygen consumption, heart rate and oxygen pulse associated with selected exercise-to-muscle class elements.
Authors: P Abernethy, P Batman
Journal: British Journal of Sports Medicine (1994)

The purpose of the investigation was to determine the relative oxygen consumption (VO2), heart rate and oxygen pulse associated with the constituent elements of an exercise-to-music class. Six women exercise-to-music leaders with a mean(s.d.) age, weight and height of 33.2(5.2) years, 51.0(2.8) kg and 157.9(5.6) cm respectively, completed five distinct exercise-to-music movement elements. The movement elements were of a locomoter (circuit, jump and low impact) and callisthenic (prone and side/supine) nature. The movement elements were distinguishable from one another in terms of their movement patterns, posture and tempo. Relative VO2 values were greatest for the circuit element (40.6 ml kg-1 min-1) and least for the side/supine element (20.0 ml kg-1 min-1). The differences in VO2 between the locomotrr and callisthenic elements were significant (circuit approximately jump approximately low impact > prone approximately side/supine). However, effect size data suggested that the differences between the low impact and jump elements and the prone and side/supine elements were of practical significance (circuit approximately jump > low impact > prone > side/supine). With a single exception similar parametric statistics and effect size trends were identified for absolute heart rate. Specifically, the heart rate associated with the low impact element was not significantly greater than the prone element. The oxygen pulse associated with the locomotor elements was significantly greater than the callisthenic elements (circuit approximately jump approximately low impact > prone > side/supine). This suggested that heart rate may be an inappropriate index for making comparisons between exercise-to-music elements. Reasons for differences in oxygen uptake values between movement elements are discussed.
Authors reply: Diagnosis of a single imported dengue case who had travelled to Japan – how serious is it for travellers?
Authors: N G Schwarz, B Kreuels, K Stark, C Frank, J Schmidt-Chanasit
Journal: Eurosurveillance (2014)

Preview this article: Authors reply: Diagnosis of a single imported dengue case who had travelled to Japan – how serious is it for travellers?, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/19/8/art20716-en-1.gif