tbuckley/cabot-search huggingface dataset:
Universal HIV testing in London tuberculosis clinics: a cluster randomised controlled trial
Authors: Anjana Roy, Sudy Anaraki, Pia Hardelid, Mike Catchpole, Laura C. Rodrigues, Marc Lipman, Samantha Perkins, Anita Roche, Helen R. Stagg, Jose Figueroa, Ibrahim Abubakar
Journal: European Respiratory Journal (2012)

We assessed whether implementation of a combination of interventions in London tuberculosis clinics raised the levels of HIV test offers, acceptance and coverage. A stepped-wedge cluster randomised controlled trial was conducted across 24 clinics. Interventions were training of clinical staff and provision of tailor-made information resources with or without a change in clinic policy from selective to universal HIV testing. The primary outcome was HIV test acceptance amongst those offered a test, before and after the intervention; the secondary outcome was an offer of HIV testing. Additionally, the number and proportion of HIV tests among all clinic attendees (coverage) was assessed. 1,315 patients were seen in 24 clinics. The offer and coverage of testing rose significantly in clinics without (p = 0.002 and p = 0.004, respectively) and with an existing policy of universal testing (p = 0.02 and p = 0.04, respectively). However, the level of HIV test acceptance did not increase in 18 clinics without routine universal testing (p = 0.76) or the six clinics with existing universal testing (p = 0.40). The intervention significantly increased the number of HIV tests offered and proportion of participants tested, although acceptance did not change significantly. However, the magnitude of increase is modest due to the high baseline coverage.
EUROSCAN, a Randomized Trial of Vitamin A and N-Acetylcysteine in Patients With Head and Neck Cancer or Lung Cancer
Authors: N. van Zandwijk
Journal: JNCI Journal of the National Cancer Institute (2000)

Background: Preclinical evidence suggests that retinoids and antioxidants may prevent or delay the occurrence of cancer in the upper or lower airways, but such effects have not been reliably established in clinical studies. To assess the chemopreventive effects of vitamin A (retinyl palmitate) and N-acetylcysteine, we conducted a large randomized intervention study in patients with head and neck cancer or with lung cancer, most of whom had a history of smoking. Methods: From June 1988 through July 1994, a total of 2592 patients (60% with head and neck cancer and 40% with lung cancer) were randomly assigned to receive 1) retinyl palmitate (300000 IU daily for 1 year followed by 150000 IU for a 2nd year), 2) N-acetylcysteine (600 mg daily for 2 years), 3) both compounds, or 4) no intervention. All statistical tests were two-sided. Results: Of the patients, 93.5% had smoked tobacco at sometime in their lives (and 25% continued to smoke after cancer diagnosis). After a median follow-up of 49 months, 916 patients were reported with an event (recurrence, second primary tumor, or death). No statistically significant difference was observed in overall survival or event-free survival between patients who received retinyl palmitate and patients who did not. Similarly, no difference was seen in overall survival or event-free survival between patients who received N-acetylcysteine and patients who did not. There was a lower incidence of second primary tumors in the no intervention arm, but the difference was not statistically significant. Conclusion: A 2-year supplementation of retinyl palmitate and/or N-acetylcysteine resulted in no benefit—in terms of survival, event-free survival, or second primary tumors—for patients with head and neck cancer or with lung cancer, most of whom were previous or current smokers.
Survivin Is a Viable Target for the Treatment of Malignant Peripheral Nerve Sheath Tumors
Authors: Markus P. Ghadimi, Eric D. Young, Roman Belousov, Yiqun Zhang, Gonzalo Lopez, Kristelle Lusby, Christine Kivlin, Elizabeth G. Demicco, Chad J. Creighton, Alexander J. Lazar, Raphael E. Pollock, Dina Lev
Journal: Clinical Cancer Research (2012)

Abstract Purpose: To examine the role of survivin as a therapeutic target in preclinical models of human malignant peripheral nerve sheath tumors (MPNST) Experimental Design: Survivin protein expression levels and subcellular localization were examined immunohistochemically in an MPNST tissue microarray. Human MPNST cells were studied in vitro and in vivo; real-time PCR, Western blotting, and immunocytochemical analyses were used to evaluate survivin expression and localization activation. Cell culture assays were used to evaluate the impact of anti-survivin–specific siRNA inhibition on cell growth and cell-cycle progression and survival. The effect of the small-molecule survivin inhibitor YM155 on local and metastatic MPNST growth was examined in vivo. Results: Survivin was found to be highly expressed in human MPNSTs; enhanced cytoplasmic subcellular localization differentiated MPNSTs from their plexiform neurofibroma premalignant counterparts. Human MPNST cell lines exhibited survivin mRNA and protein overexpression; expression in both nuclear and cytoplasmic compartments was noted. Survivin knockdown abrogated MPNST cell growth, inducing G2 cell-cycle arrest and marked apoptosis. YM155 inhibited human MPNST xenograft growth and metastasis in severe combined immunodeficient (SCID) mice. Antitumor effects were more pronounced in fast-growing xenografts. Conclusions: Our studies show an important role for survivin in human MPNST biology. Patients with MPNSTs should be considered for ongoing or future clinical trials that evaluate anti-survivin therapeutic strategies. Most importantly, future investigations should evaluate additional pathways that can be targeted in combination with survivin for maximal synergistic anti-MPNST effects. Clin Cancer Res; 18(9); 2545–57. ©2012 AACR.
Epigenetic Resensitization to Platinum in Ovarian Cancer
Authors: Daniela Matei, Fang Fang, Changyu Shen, Jeanne Schilder, Alesha Arnold, Yan Zeng, William A. Berry, Tim Huang, Kenneth P. Nephew
Journal: Cancer Research (2012)

Preclinical studies have shown that hypomethylating agents reverse platinum resistance in ovarian cancer. In this phase II clinical trial, based upon the results of our phase I dose defining study, we tested the clinical and biologic activity of low-dose decitabine administered before carboplatin in platinum-resistant ovarian cancer patients. Among 17 patients with heavily pretreated and platinum-resistant ovarian cancer, the regimen induced a 35% objective response rate (RR) and progression-free survival (PFS) of 10.2 months, with nine patients (53%) free of progression at 6 months. Global and gene-specific DNA demethylation was achieved in peripheral blood mononuclear cells and tumors. The number of demethylated genes was greater (P < 0.05) in tumor biopsies from patients with PFS more than 6 versus less than 6 months (311 vs. 244 genes). Pathways enriched at baseline in tumors from patients with PFS more than 6 months included cytokine-cytokine receptor interactions, drug transporters, and mitogen-activated protein kinase, toll-like receptor and Jak-STAT signaling pathways, whereas those enriched in demethylated genes after decitabine treatment included pathways involved in cancer, Wnt signaling, and apoptosis (P < 0.01). Demethylation of MLH1, RASSF1A, HOXA10, and HOXA11 in tumors positively correlated with PFS (P < 0.05). Together, the results of this study suggest that low-dose decitabine altered DNA methylation of genes and cancer pathways, restoring sensitivity to carboplatin in patients with heavily pretreated ovarian cancer and resulting in a high RR and prolonged PFS.
Relationship of proteinases and proteinase inhibitors with microbial presence in chronic lung disease of prematurity
Authors: P. L Davies, O B. Spiller, M. L Beeton, N. C Maxwell, E. Remold-O'Donnell, S. Kotecha
Journal: Thorax (2010)

<h3>Background</h3> A proteolytic imbalance has been implicated in the development of "classical" chronic lung disease of prematurity (CLD). However, in "new" CLD this pattern has changed. This study examines the longitudinal relationship between neutrophil proteinases and their inhibitors in ventilated preterm infants and their relationship to microbial colonisation. <h3>Methods</h3> Serial bronchoalveolar lavage fluid was obtained from ventilated newborn preterm infants. Neutrophil elastase (NE) activity, cell counts, metalloproteinase (MMP)-9, MMP-9/TIMP-1 complex, SerpinB1 concentration and percentage of SerpinB1 and α<sub>1</sub>-antitrypsin (AAT) in complex with elastase were measured. The presence of microbial genes was examined using PCR for 16S rRNA genes. <h3>Results</h3> Statistically more infants who developed CLD had NE activity in at least one sample (10/20) compared with infants with resolved respiratory distress syndrome (RDS) (2/17). However, NE activity was present in a minority of samples, occurring as episodic peaks. Peak levels of MMP-9, MMP-9/TIMP-1 complex, percentage of AAT and SerpinB1 in complex and cell counts were all statistically greater in infants developing CLD than in infants with resolved RDS. Peak values frequently occurred as episodic spikes and strong temporal relationships were noted between all markers. The peak values for all variables were significantly correlated to each other. The presence of bacterial 16S rRNA genes was associated with the development of CLD and with elevated elastase and MMP-9. <h3>Conclusion</h3> NE activity and MMP-9 appear to be important in the development of "new" CLD with both proteinase and inhibitor concentrations increasing episodically, possibly in response to postnatal infection.
Manifest and Concealed Reentry: A MECHANISM OF AV NODAL WENCKEBACH PHENOMENON
Authors: ANTHONY N. DAMATO, P. Jacob VARGHESE, SUN H. LAU, JOHN J. GALLAGHER, GUSTAVUS A. BOBB
Journal: Circulation Research (1972)

The mechanism of the AV nodal Wenckebach phenomenon was studied in 25 dogs by multiple atrial and His bundle electrogram (HBE) recordings. During ventricular stimulation with 1:1 retrograde conduction, the interval from the stimulus artifact to the retrograde His deflection (S-H) interval) remained constant. Decreasing the cycle length of stimulation (CLS) resulted in retrograde AV nodal Wenckebeach cycles. When retrograde AV nodal delay reached a critical value, the Wenckebach cycles were terminated by a reciprocal beat (manifest reentry). The His bundle and ventricles were antegradely depolarized by the reentrant impulse. A further decrease in CLS produced what electrocardiographically looked like ordinary Wenckebach cycles. However, the HBE tracing revealed that reentry was occurring but was concealed by the CLS. This was confirmed by noting that the His deflection of the last ventricular paced beat of the Wenckebach cycle was antegradely depolarized and had a shorter S-H interval then all other beats of that cycle. The reentrant and retrograde impulses collided in the bundle-branch system. Further decreases in CLS masked the reentrant phenomenon on both standard ECG and HBE tracings. The S-H interval remained constant for all ventricular paced beats of the Wenckebach cycle. Under these circumstances, reentry could still be uncovered by turning off the stimulator at an appropriate time during the Wenckebach cycle. This maneuver exposed the reciprocal beat. Thus collision of the reentrant and retrograde impulses occurred within the AV node. These findings provide a satisfactory explanation for why the last beat of the Wenckebach cycle is not conducted retrogradely to the atria.
Chronic Inflammatory IFN-γ Signaling Suppresses Hepatocarcinogenesis in Mice by Sensitizing Hepatocytes for Apoptosis
Authors: Stefan Lüth, Jörg Schrader, Stefan Zander, Antonella Carambia, Juliane Buchkremer, Samuel Huber, Kurt Reifenberg, Ken-Ichi Yamamura, Peter Schirmacher, Ansgar W. Lohse, Johannes Herkel
Journal: Cancer Research (2011)

Chronic liver inflammation is a critical component of hepatocarcinogenesis. Indeed, inflammatory mediators are believed to promote liver cancer by upholding compensatory proliferation of hepatocytes in response to tissue damage. However, inflammation can also mediate the depletion of malignant cells, but the difference between tumor-suppressive and tumor-promoting inflammation is not defined at the molecular level. Here, we analyzed the role of the major inflammatory mediator IFN-γ in chemical hepatocarcinogenesis of transgenic mice that overexpress IFN-γ in the liver; these mice manifest severe chronic inflammatory liver damage and lasting compensatory regeneration. We found that chronic exposure to IFN-γ suppressed chemical hepatocarcinogenesis, despite overt liver injury. Indeed, IFN-γ-transgenic mice had significantly fewer and significantly less advanced malignant lesions than nontransgenic mice. This tumor-suppressive effect of IFN-γ seemed to be mediated in part by its known immune activating function, indicated by infiltration of IFN-γ-transgenic livers with CD8 T cells, natural killer T cells, and natural killer cells. However, IFN-γ seemed to prevent carcinogenesis also by activating the cell-intrinsic p53 tumor suppressor pathway. Indeed, exposure to IFN-γ in vivo or in vitro was associated with accumulation of p53 in hepatocytes and the sensitization of hepatocytes to apoptosis induced by genotoxic stress. The IFN-γ-induced increase in apoptosis of hepatocytes seemed to be p53 dependent. Thus, chronic inflammation dominated by IFN-γ may prevent hepatocarcinogenesis, despite continued inflammatory liver injury and regeneration. Therefore, the carcinogenic potential of inflammation seems to be determined by type and composition of its mediators and manipulating the type of chronic inflammation may serve the prevention of cancer.
A Mechanism for Reentry in Canine Ventricular Tissue
Authors: BETTY I. SASYNIUK, CARLOS MENDEZ
Journal: Circulation Research (1971)

In isolated canine papillary muscle-false tendon preparations it was possible by selecting the pattern of stimulation to obtain conduction block within the peripheral distribution of the Purkinje network. Action potentials recorded just proximal to the site of block were always extremely brief in duration; refractory periods were abbreviated accordingly. When propagation from specialized fibers to muscle fibers was made very critical, conduction block occurred at some Purkinje-muscle junctions while propagation continued through others. Under these conditions very early reentrant activity could be obtained in terminal Purkinje fibers. With proper timing, the impulse propagated back to the false tendon and emerged as a closely coupled extrasystole. Occasionally, the activity returned again to muscle and resulted in a double reentry. Electrotonic shortening of action potentials of Purkinje fibers at relatively long distances upstream from a site of block facilitated the reentry of proximal elements. Partial reentry of the Purkinje system created conditions favoring fractionation of the reentrant wave front.
Verification of a formula for determination of preexcision surgical margins from fixed-tissue melanoma specimens
Authors: Mark K. Silverman, Frederick M. Golomb, Alfred W. Kopf, Caron M. Grin-Jorgensen, Katrien A. Vossaert, Joyce P. Doyle, Marcia J. Levenstein
Journal: Journal of the American Academy of Dermatology (1992)

Recently our group reported on the shrinkage of 199 malignant melanoma surgical-excision specimens. In that report, a multivariate analysis revealed that the age of the patient was the only factor that significantly affected the percentage shrinkage of a surgical specimen. In addition, a formula was presented that extrapolates the actual surgical margins (in vivo) from the (contracted) fixed-tissue pathology report measurement and the reported in vivo lesion diameter.The goals of this study are to verify that shrinkage of surgical specimens is approximately 20% and that the margin formula can be successfully applied to a different group of patients.Four hundred seven patients with malignant melanoma were prospectively enrolled to measure preexcision (outlined with ink) surgical margins, fixed-tissue (contracted) surgical margins, and overall specimen shrinkage.It is verified that overall shrinkage of cutaneous surgical specimens is approximately 20%. Surgical specimens from patients younger than 50 years of age have approximately 25% shrinkage. Those specimens from patients 50 to 59 years of age have approximately 20% shrinkage and those from patients 60 years of age or older have about 15% shrinkage. The surgical margins predicted by the margin formula were within +/- 3.5 mm of the actual measured surgical margin 86.5% of the time.The actual surgical margins (in vivo) of a malignant melanoma can be reasonably estimated from the fixed-tissue pathology measurement via the margin formula. The shrinkage of a surgical specimen is 15% to 25% depending on the patient's age.
Effect of pulmonary rehabilitation on gas exchange, muscle cross section area and functional parameters in interstitial lung disease
Authors: Balakrishnan Menon, V.K. Vijayan, Vishal Bansal, Brijesh Prajapat
Journal: European Respiratory Journal (2011)

Introduction:  Pulmonary rehabilitation has an important role in the management of interstitial lung diseses (ILD). This study evaluates effect of pulmonary rehabilitation on gas exchange, muscle cross sectional area and functional parameters in patients of ILD.   Aims and objectives:  To evaluate 6 minute walk distance (6MWD), Mid Thigh Cross Sectional Area on CT (MTCSA CT ) and Carbon Monoxide Diffusion Capacity (DLCO) before and after pulmonary rehabilitation in patients of ILD.   Methods:  Twenty eight patients of ILD were randomly allocated to Control and Test groups. The control group received standard medications for 8 weeks while the test group was given supervised pulmonary rehabilitation along with standard medications for 8 weeks.   Results:  Mean values of 6MWD changed from 476.50±61.97 m to 482.64±58.33 m in control group [p=0.369]and from 455.64±63.55 m to 509.78±69.03 m in test group [p=0.015].  Levels of DLCO changed from 11.88±4.38 ml/min/mmHg to 11.62±4.00 ml/min/mmHg in control group [p=0.399] and from 10.80±3.73 ml/min/mmHg to 13.08±3.87 ml/min/mmHg [p=0.004] in test group.  Mean values of MTCSA CT  changed from 9311.21±1987.21 cm 2  to 9271.07±1918.42 cm 2  in control group [p=0.646] and from 9485.21±2083.44 cm 2  to 10330.71±2137.41 cm 2  in test group [p=0.031].  The difference of means between control and test groups after pulmonary rehabilitation was significant for DLCO, MTCSA CT  and 6MWD. Positive correlation was obtained between MTCSA CT  and 6MWD [r=0.7, p=0.006].   Conclusion:  Pulmonary rehabilitation causes significant improvement in muscle cross sectional area and functional parameters in ILD patients along with significant improvement in gas exchange.
Randomized trial of low molecular weight heparin (enoxaparin) versus unfractionated heparin for unstable coronary artery disease∗∗∗∗A list of participating ESSENCE Study Group investigators may be found in N Engl J Med 1997;337:447–52.
Authors: Shaun G Goodman, Marc Cohen, Frederique Bigonzi, David R Radley, Gregg J Fromell, Enrique P Gurfinkel, Veronique Le Iouer, Christine Demers, Alexander G.G Turpie, Robert M Califf, Keith A.A Fox, Anatoly Langer
Journal: Journal of the American College of Cardiology (2000)
SSeCKS Metastasis-Suppressing Activity in MatLyLu Prostate Cancer Cells Correlates with Vascular Endothelial Growth Factor Inhibition
Authors: Bing Su, Qiao Zheng, Mary M. Vaughan, Yahao Bu, Irwin H. Gelman
Journal: Cancer Research (2006)

Abstract SSeCKS, a Src-suppressed protein kinase C substrate with metastasis suppressor activity, is the rodent orthologue of human gravin/AKAP12, a scaffolding protein for protein kinase A and protein kinase C. We show here that the tetracycline-regulated reexpression of SSeCKS in MatLyLu (MLL) prostate cancer cells suppressed formation of macroscopic lung metastases in both spontaneous and experimental models of in vivo metastasis while having minimal inhibitory effects on the growth of primary-site s.c. tumors. SSeCKS decreased angiogenesis in vitro and in vivo by suppressing vascular endothelial growth factor (VEGF) expression in MLL tumor cells as well as in stromal cells. The forced reexpression of VEGF165 and VEGF121 isoforms was sufficient to reverse aspects of SSeCKS metastasis-suppressor activity in both the experimental and spontaneous models. SSeCKS reexpression in MLL cells resulted in the down-regulation of proangiogenic genes, such as osteopontin, tenascin C, KGF, angiopoietin, HIF-1α, and PDGFRβ, and the up-regulation of antiangiogenic genes, such as vasostatin and collagen 18a1, a precursor of endostatin. These results suggest that SSeCKS suppresses formation of metastatic lesions by inhibiting VEGF expression and by inducing soluble antiangiogenic factors. (Cancer Res 2006; 66(11): 5599-607)
Risk Factors for Tuberculosis among HIV-infected Patients Receiving Antiretroviral Treatment
Authors: Stephen D. Lawn, Motasim Badri, Robin Wood
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Although tuberculosis (TB) incidence among HIV-infected cohorts receiving highly active antiretroviral treatment (HAART) is reduced by 70–90%, it remains substantially higher than among HIV-noninfected patients (1, 2). Strategies to reduce the burden ofTBduringHAARTare needed.We therefore readwith interest the article by Seyler and colleagues, which reported risk factors for TB among patients receiving HAART in Abidjan (3). Using multivariate analysis, Seyler and colleagues found that a past history of TB was the only significant risk factor for TB during HAART (3). The 31 patients in the cohort with a past history of TB had all been declared cured following 6 mo or more of rifampicin-containing anti-TB treatment, and yet six developed TB during HAART over a median of 26 mo observation. This represents an unusually high recurrence rate (4) even without taking into account the major protective effect of HAART. Of note, however, 33% of the incident cases were smearand culture-negative; potential misdiagnoses of active TB among patients with symptomatic posttuberculous lung disease may have confounded past history of TB as a risk factor. Advanced immunodeficiency might be expected to be associated with an ongoing increased risk of TB during HAART, at least until a satisfactory degree of immune restoration has been achieved. We have studied a large cohort in Cape Town (described in Reference 2) that includes patients with a diverse range of CD4 cell counts and clinical stages. Analysis reveals that the ongoing risk of TB during HAART is much greater among those with low nadir CD4 cell counts and advanced clinical stage of disease; past history of TB is not a risk factor. The disparities with the findings of Seyler and colleagues may reflect differences in diagnostic criteria for TB and the fact that the restricted enrollment criteria for the Abidjan cohort resulted in inclusion of few patients with stage 1 or 2 disease or CD4 cell counts greater than 200 cells/ l; the resulting cohort composition diminishes the power to assess CD4 count and clinical stage as risk factors. This is a problem common to analysis of data from many cohorts receiving HAART in Africa where often only those with advanced disease are treated. If it is confirmed that the risk of TB during HAART is associated with advanced pretreatment immunodeficiency, the risk might be decreased by earlier initiation of HAART. In addition, those patients with advanced immunodeficiency may derive greatest benefit from adjunctive treatments such as isoniazid prophylaxis.