tbuckley/cabot-search huggingface dataset:
Seizure prophylaxis in patients with brain metastases from solid tumors: Is phenytoin necessary?
Authors: S. Evans, N. Jooma, A. Kabir, L. Nedzi, E. Zakris, R. Mudad
Journal: Journal of Clinical Oncology (2004)

8186 Background: The use of phenytoin as primary seizure prophylaxis in patients with brain metastases from solid tumors is widely practiced at our institution, although this has fallen out of favor in the literature. There are concerns over p450 interactions between phenytoin and standard chemotherapy regimens. We sought to determine the incidence of seizures in patients with brain metastases with or without prophylaxis, as well as the percentage of those patients receiving chemotherapy. Methods: We performed a retrospective review of patients with brain metastases from solid tumors from 1997–2002. Patients were identified through the tumor registries of Tulane affiliated hospitals. Cases were excluded if there was no tissue diagnosis, or if there were spinal cord metastases only. Demographic information, phenytoin use, prevalence of seizures, date of tissue diagnosis, date of death, and presenting symptoms were recorded. All treatments were recorded. Results: Eighty-eight patients were identified. Non-small cell lung carcinoma was the most common histology, representing 79.5% of patients. Median overall survival of all patients was 128 days. Thirty-nine patients received prophylactic phenytoin, and of those, twenty-one patients (51%) subsequently developed seizures. Forty-seven patients (53%) were not on phenytoin and four (8.5%) subsequently developed seizures. Thirteen patients (32%) received phenytoin and chemotherapy, while ten patients (21%) received chemotherapy alone. Median survival in the former group was 267 days, while in the latter it was 120 days. Conclusions: Paradoxically, seizure development was more common in the group receiving phenytoin, indicating that primary prophylaxis was ineffective, and may not be necessary. Data on neurosurgical intervention in both groups, possibly explaining the difference, will be analyzed and reported at the meeting. Survival differences between the chemotherapy groups will also be analyzed to evaluate its statistical significance. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis
STUDIES UPON EXPERIMENTAL PNEUMONIA IN RABBITS
Authors: B. S. Kline, M. C. Winternitz
Journal: The Journal of Experimental Medicine (1915)

1. The production of lobar pneumonia in rabbits is dependent upon the introduction of organisms into the alveoli themselves. 2. In order to accomplish this the catheter through which they are injected must be inserted as deeply into a bronchus as possible and the culture fluid injected with considerable force. 3. Large numbers of organisms injected into the trachea just beyond the larynx set up no great changes in the lungs, even though the injection be forcible. This fact suggests the presence of a protective mechanism in the upper air passages, which, under normal conditions, prevents the penetration of organisms into the lungs. 4. If animals be subjected to cold, alcohol, and the inhalation of irritating gases, the so called secondary factors in the etiology of lobar pneumonia in man, then the injection of pneumococci into the trachea causes inflammatory changes of the upper respiratory tract and occasionally pneumonia. 5. The vagi prevent foreign material in the pharynx and upper respiratory tract from reaching the lungs. Section of one vagus may be followed by pneumonia, while section of both invariably leads to this result. 6. It is possible that the secondary factors mentioned above owe their action to their influence upon the vagus control of the upper respiratory tract.
AMSSM scientific statement concerning viscosupplementation injections for knee osteoarthritis: importance for individual patient outcomes
Authors: Thomas H Trojian, Andrew L Concoff, Susan M Joy, John R Hatzenbuehler, Whitney J Saulsberry, Craig I Coleman
Journal: British Journal of Sports Medicine (2016)

Osteoarthritis (OA) is a disabling disease that produces severe morbidity reducing physical activity. Our position statement on treatment of knee OA with viscosupplementation injection (hyaluronic acid, HA) versus steroid (intra-articular corticosteroids, IAS) and placebo (intra-articular placebo, IAP) is based on the evaluation of treatment effect by examining the number of participants within a treatment arm who met the Outcome Measures in Rheumatoid Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) criteria, which is different and more relevant than methods used in other reviews which examined if the average change across the treatment groups were clinically different. We performed a systematic literature search for all relevant articles from 1960 to August 2014 in the MEDLINE, EMBASE and Cochrane CENTRAL. We performed a network meta-analysis (NMA) of the relevant literature to determine if there is a benefit from HA as compared with IAS and IAP. 11 papers met the inclusion criteria from the search strategy. On NMA, those participants receiving HA were 15% and 11% more likely to respond to treatment by OMERACT-OARSI criteria than those receiving IAS or IAP, respectively (p&lt;0.05 for both). In the light of the aforementioned results of our NMA, the American Medical Society for Sport Medicine recommends the use of HA for the appropriate patients with knee OA.
Treatment interruption and directly observed treatment for patients with multidrug-resistant tuberculosis in China: a cross-sectional survey
Authors: Xiaolin Wei, Jia Yin, Guanyang Zou, Zhitong Zhang, John Walley, Joseph Harwell, Haitao Li, Qiang Sun, Renzhong Li, Lixia Wang, Xiulei Zhang
Journal: The Lancet (2015)
Abstract 11242: Impact of Peripheral Artery Disease on Prognosis in Heart Failure Patients
Authors: Yuichi Nakamura, Akiomi Yoshihisa, Hiroyuki Kunii, Mai Takiguchi, Takeshi Shimizu, Hiroyuki Yamauchi, Takashi Owada, Satoshi Abe, Satoshi Suzuki, Koichi Sugimoto, Takayoshi Yamaki, Kazuhiko Nakazato, Hitoshi Suzuki, Shu-ichi Saitoh, Yasuchika Takeishi
Journal: Circulation (2014)

Background: A history of peripheral artery disease (PAD) is an independent predictor of cardiac mortality in patients with ischemic heart disease. However, it still remains unclear whether PAD predicts worsening heart failure (HF), cardiac and all-cause mortality in HF patients. Methods and Results: Consecutive 388 HF patients admitted to our hospital for the treatment of decompensated HF were divided into 2 groups based on the presence of PAD: HF with PAD (PAD group, n = 103) and HF without PAD (non-PAD group, n = 285). We compared echocardiographic and laboratory findings, and followed the event of worsening HF, cardiac death, non-cardiac death, and all-cause mortality between the two groups. The PAD group, as compared to non-PAD group, had 1) higher age (69.2 vs. 64.5 years old, P=0.001), 2) higher incidence of New York Heart Association functional class III or IV (56.3% vs. 37.2%, P = 0.001), 3) lower levels of hemoglobin (12.3 vs. 12.9 g/dl, P = 0.020), 4) higher levels of B-type natriuretic peptide (591.0 vs. 256.9 pg/ml, P = 0.017), 5) lower estimated glomerular filtration rate (GFR) (46.2 vs. 58.9 ml/min/1.73m 2 , P &lt; 0.001), and 6) lower left ventricular ejection fraction (42.0 vs. 48.7%, P &lt; 0.001). In the follow-up period (mean 765.6 days), Kaplan-Meier analyses (Figure) showed that the event-free survival from worsening HF, cardiac death, non-cardiac death and all-cause death was significantly higher in non-PAD group than in PAD group (P = 0.017, P &lt; 0.001, P = 0.001 and P = 0.005, respectively, by a log-rank test). In the Cox proportional hazard analyses after adjusting for age, gender, ejection fraction, estimated GFR, and the presence of ischemic heart disease, PAD was an independent predictor of cardiac death (hazard ratio (HR) 2.09, P = 0.019) and all-cause mortality (HR 2.16, P = 0.002) in HF patients. Conclusions: PAD is an independent predictor of cardiac mortality and all-cause mortality in HF patients.
Blood pressure change after treatment for obstructive sleep apnoea (OSA) with continuous positive airway pressure (CPAP)
Authors: Jct Pepperell, B Mullins, N Crosthwaite, Stradling, Rjo Davies
Journal: Thorax (2000)

It is unclear whether OSA is an independent risk factor for hypertension and whether CPAP treatment reduces blood pressure (BP). We conducted a randomised parallel controlled trial of 4 weeks therapeutic versus sub-therapeutic CPAP treatment (as a control) in men with OSA (Epworth Score (ESS) >10, >4% SaO2 dips >10 per hour). We measured 24-hour BP at home using the TM-2420 ambulatory BP monitoring system before and after treatment. Diary cards were used to report sleep and wake periods. BP changes with treatment were compared between groups using independent samples T-Tests. 85 patients completed the trial. Median (range), age 50 (33-73) years; Body Mass Index 33.7 (24.9-53.9); ESS 16 (10-24); SaO2 dip rate 32.1 (10.6-101.3) and similar between groups. Machine use hours CPAP per night was equivalent between therapeutic 5.4 (2.3-9) and control groups 5.5 (0.4-10). The groups had similar baseline 24 hour BP, mean (SD) therapeutic 132.7 (14.5) / 85.3 (9.5), controls 132.5 (16.6)/84.5 (9.1). Change in BP with Treatment Systolic(mmHg) Diastolic(mmHg) Overall Wake Sleep Overall Wake Sleep Therapeutic -2.4 -1.4 -5.8 -1.6 -1.9 -2.0 n=41 (1.4) (1.4) (1.8) (1.3) (1.4) (1.4) Control +1.4 +2.8 -0.4 +0.6 +1.5 -0.8 n=44 (1.3) (1.4) (1.7) (0.8) (.86) (1.3) p value <0.05 <0.05 <0.04 ns <0.05 ns Mean change (SEM) in Systolic and Diastolic BP by treatment group. Post treatment, sleep period systolic BP was also significantly different on a between groups comparison of means, therapeutic mean (SD) 118.1 (13.3) mmHg versus control 125.6 (18.4), p<0.05. These results support OSA as an independent risk factor for the elevation of blood pressure in men, and shows a blood pressure fall with CPAP treatment.
Replacement of brain-resident myeloid cells does not alter cerebral amyloid-β deposition in mouse models of Alzheimer’s disease
Authors: Nicholas H. Varvel, Stefan A. Grathwohl, Karoline Degenhardt, Claudia Resch, Andrea Bosch, Mathias Jucker, Jonas J. Neher
Journal: The Journal of Experimental Medicine (2015)

Immune cells of myeloid lineage are encountered in the Alzheimer’s disease (AD) brain, where they cluster around amyloid-β plaques. However, assigning functional roles to myeloid cell subtypes has been problematic, and the potential for peripheral myeloid cells to alleviate AD pathology remains unclear. Therefore, we asked whether replacement of brain-resident myeloid cells with peripheral monocytes alters amyloid deposition in two mouse models of cerebral β-amyloidosis (APP23 and APPPS1). Interestingly, early after repopulation, infiltrating monocytes neither clustered around plaques nor showed Trem2 expression. However, with increasing time in the brain, infiltrating monocytes became plaque associated and also Trem2 positive. Strikingly, however, monocyte repopulation for up to 6 mo did not modify amyloid load in either model, independent of the stage of pathology at the time of repopulation. Our results argue against a long-term role of peripheral monocytes that is sufficiently distinct from microglial function to modify cerebral β-amyloidosis. Therefore, myeloid replacement by itself is not likely to be effective as a therapeutic approach for AD.
Justifying conflicts of interest in medical journals: a very bad idea
Authors: R. Steinbrook, J. P. Kassirer, M. Angell
Journal: BMJ (2015)

A series of articles in the <i>New England Journal of Medicine</i> has questioned whether the conflict of interest movement has gone too far in its campaign to stop the drug industry influencing the medical profession. Here, three former senior <i>NEJM</i> editors respond with dismay
Liver function tests in patients with acute heart failure and associated outcomes: insights from ASCEND-HF
Authors: Marc D. Samsky, Allison Dunning, Adam D. DeVore, Phillip J. Schulte, Randall C. Starling, W.H. Wilson Tang, Paul W. Armstrong, Justin A. Ezekowitz, Javed Butler, John J. McMurray, John R. Teerlink, Adrian A. Voors, Marco Metra, Robert J. Mentz, Christopher M. O'Connor, Chetan B. Patel, Adrian F. Hernandez
Journal: European Journal of Heart Failure (2015)
Determinants of FDG Uptake in Atherosclerosis⁎⁎Editorials published in JACC: Cardiovascular Imaging reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Imaging or the American College of Cardiology.
Authors: Christoph Buettner, James H.F. Rudd, Zahi A. Fayad
Journal: JACC. Cardiovascular imaging (2011)
Afferent vagal modulation of ventilation and compensatory capacity of the respiratory system at obstructive lung disease with central hypervolemia: A modeling study
Authors: Zhanna Donina
Journal: European Respiratory Journal (2014)

Objective: Our hypothesis is that the afferent information from lung receptors takes part in the control mechanism of ventilation and compensatory capacity of the respiratory system at obstructive lung disease with central hypervolemia.  Methods: Head-down tilt (HDT) that increase central venous pressure due to fluid shifts within the entire body was used as model for simulating central hypervolemia. The experiments were performed in vagaly intact or vagotomized, anesthetized rats. Tidal volume (VT), breathing frequency (f), minute lung ventilation (VE), esophageal pressure (Pes), inspiratory occlusion pressure (P 0.1 ), functional residual capacity (FRC), lung compliance (C), central venous pressure (CVP) were examined at supine (baseline) and after 30 min HDT.  Results: HDT increase of CVP, decrease of FRC and C. There were significant decreases in VT by 18%, VE by 14% after 30 min exposure in HDT relative to supine. Increases resistive and elastic component of respiratory resistance were found. On the other hand rising Pes by 116% wasseen which reflects an increase in inspiratory muscle output occurs when respiratory load increases. After bilateral vagotomy Pes rose only to 65% in comparison to vagal intact animals. Inspiratory occlusion pressure evoked increase P 0.1  in both supine and HDT. In supine this value rose to 536% (Pl0.01), whereas in HDT by 320% (Pl0.05).  Conclusions: One of the possible mechanism of compensatory response respiratory system is the vagal afferent, presumably originating from slowly adapting lung stretch receptors due to decreased lung volume.
Abstract 15954: Both Tetrahydrobiopterin Depletion and eNOS S-Glutathionytion Contribute to eNOS Uncoupling in Coronary Disease Patients
Authors: Saradhadevi Varadharaj, Francesco DePascali, Juan Crestanello, Ahmet Kilic, James Boslett, Craig Hemann, Chun-An Chen, Jay L Zweier
Journal: Circulation (2014)

Background: Vascular endothelial dysfunction (VED) is associated with increased oxidative stress due to eNOS uncoupling with increased superoxide (•O2-) production and has important prognostic clinical implications for subsequent cardiovascular events. Our recent studies in hypertensive rats revealed a novel redox-regulated pathway through which eNOS is uncoupled due to S-glutathionylation. However, its role in human vascular disease remains unclear. Hence, we studied eNOS S-glutathionylation and uncoupling and in aortic tissue from patients undergoing cardiovascular surgery and heart transplantation (N=25). Methods: Studies were performed using vessels from spontaneously hypertensive rats (SHRs), control WKY rats and aortic tissue from patients undergoing cardiovascular surgery. S-glutathionylation was determined with anti-glutathione and anti-eNOS, and an antibody specific for eNOS S-glutathionylation at C689 (anti-eNOS Cys689-SG). •O2- was measured using fluorescent probe DHE in the absence/presence of the NOS inhibitor, L-NAME, DTT, or the SOD mimetic, MnTBAP. The NOS cofactor, BH4, was measured by HPLC. Results &amp; Conclusion: S-glutathionylation of eNOS (eNOS-SG) was evident by immunohistology in SHR vessels compared to respective WKY control rat vessels. Similarly, immune assays of the aortic samples from vascular disease patients (VD) showed an increase in eNOS-SG protein when compared to no-disease control tissues (ND) and increased •O2- production was detected. Addition of DTT or β-ME decreased the levels of eNOS-SG with decreased •O2- generation. BH4 content was markedly decreased in the vessels of patients with coronary disease. BH4:BH2 ratio was decreased by over 5-fold also contributing to eNOS uncoupling. This provides the first evidence for an association of both eNOS S-glutathionylation and BH4 depletion leading to eNOS uncoupling with loss of endothelial dependent vasodilation in vessels of coronary disease patients.
Reassessing the boundaries of liver transplantation for hepatocellular carcinoma: Where do we stand with tumor down‐staging?
Authors: Francis Y Yao, Nicholas Fidelman
Journal: Hepatology (2007)

Down-staging of hepatocellular carcinoma prior to liver transplantation (LT) has generated a lot of interest in recent years and has been identified in two recent national conferences on hepatocellular carcinoma as one of the priorities for research. Down-staging is defined as reduction in the tumor burden using local regional therapy specifically to meet acceptable criteria for LT. The rationale behind down-staging of tumors initially exceeding conventional criteria for LT is to select a subgroup of tumors with favorable biology and prognosis for LT as assessed by their response to local regional therapy. The expectation is to achieve comparable posttransplant survival between patients who achieve successful tumor down-staging before LT and those whose tumors meet LT criteria at the outset without needing down-staging. The application of tumor down-staging requires a highly structured approach using a treatment protocol that includes five essential components: eligibility criteria, down-staging endpoints, selection of the type of local regional therapy, minimal observation period from successful tumor down-staging to LT, and criteria for treatment failure and exclusion from LT. This review article summarizes published data on down-staging and addresses key questions related to each of the components of the down-staging protocol as well as treatment efficacy.Based on a review of published data and recommendations from recent national and international conferences on hepatocellular carcinoma and LT, a standardized down-staging protocol is proposed to further evaluate the feasibility and efficacy of applying tumor down-staging on a broader scale.
Abstract #5492: Dihydroartemisinin is a potent anticancer drug active in hypoxic conditions
Authors: Teona Ontikatze, René Handrick, Kerstin-Daniela Bauer, Florian Freier, Amelie Rübel, Claus Belka, Verena Jendrossek
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Introduction: Tissue hypoxia is an important determinant of resistance to standard chemo- and radiotherapy. Acute hypoxia hampers the formation of reactive oxygen species (ROS) thereby reducing the manifestation of therapy-induced DNA-damage. Apoptosis signaling also involves the intermediate formation of ROS. Properties of endoperoxides as mediators of ROS provide a rationale for their potential application in tumor treatment. The radical forming antimalaria drug artemisinin exerts promising cytotoxic effects on tumor cells. Aim of our present study was to evaluate the antineoplastic potential of its derivative dihydroartemisinin (DHA) focusing on the role of proapoptotic proteins involved in mitochondrial apoptosis and mechanisms of action at low oxygen concentration (pO2=0.2%). Methods: Cell death in HCT116 Bax-/Bak-positive after treatment with DHA (12.5-50 micro\#924;), in normoxia (21%O2) or hypoxia (0.2%O2) was analyzed by fluorescence microscopy (cytochrome c release), flow cytometry (mitochondrial membrane potential, DNA fragmentation) and immunoblotting (caspase 3 and PARP cleavage). The cells were allowed to adapt to low oxygen by stabilization of HIF-1alpha before treatment as evaluated by Western blot. To elucidate the importance of intact apoptotic signaling for DHA mediated effects, HCT116 clones lacking either Bax, Bak or Bax/Bak were used. Clonogenic death was tested by colony formation assays. Results: DHA induced apoptosis in Bax-/Bak-positive HCT116 wild type cells in a time- and dose-dependent manner yielding up to 60% apoptotic cells within 24h in normoxia accompanied by Caspase-3 activation and PARP cleavage. Apoptosis levels and eradication of clonogenic tumor cells were even increased under hypoxic conditions. Deficiency of Bax or Bak/Bax almost completely abrogated DHA-induced apoptosis independently of pO2 while deficiency of Bak was less effective in blocking apoptotic response in the HCT116 model. In contrast, clonogenic death was almost not affected by loss of Bax and or Bak in hypoxia as compared to normoxic conditions. Conclusions: Taken together DHA induces apoptosis via a mitochondrial death pathway. Proapoptotic action of DHA in our solid tumor cell model depends on functional Bax in normoxia and hypoxia. In contrast, loss of Bax and/or Bak affected clonogenic cell death only in normoxic conditions suggesting that additional modes of cell death may be operative at low oxygen concentrations. These findings suggest that DHA may be a promising agent for the treatment of solid human tumors that are often characterized by regions of tissue hypoxia.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5492.
EXPERIMENTAL EPIDEMIOLOGY OF TUBERCULOSIS
Authors: Max B. Lurie
Journal: The Journal of Experimental Medicine (1933)

73 per cent of normal rabbits exposed for about 1 year to cage mates infected with tubercle bacilli of bovine type acquired a respiratory or alimentary tuberculosis, which was fatal in 50 per cent of the cases. 63.6 per cent developed tuberculosis during the first 6 months. Of rabbits vaccinated with tubercle bacilli of human type and exposed in the same cages at the same time only 36.8 per cent acquired tuberculosis during the first 6 months. Later this resistance waned, and by the end of the year altogether 60 per cent had developed tuberculosis, of which 38 per cent succumbed. The disease in the vaccinated rabbits was shown to be of exogenous origin by the isolation in pure culture from the same rabbit of the human type bacillus from the primary infection, and of the bovine type bacillus from the naturally acquired lesion. The vaccination reduced the incidence, extent, and mortality of the disease, affected the route of infection, changed its pathological character, and retarded its progress. The disease acquired by vaccinated rabbits shared many characteristics with adult type tuberculosis in man. It is suggested that this method may be used with relative ease in studying many phases of naturally acquired tuberculosis in small laboratory animals.
Predictive Value Tools as an Aid in Chemopreventive Agent Development
Authors: Barbara K. Dunn, Vernon E. Steele, Richard M. Fagerstrom, Carol F. Topp, David Ransohoff, Christopher Cunningham, Ron Lubet, Leslie G. Ford, Barnett S. Kramer
Journal: JNCI Journal of the National Cancer Institute (2015)

Background:Over 25 years, the National Cancer Institute’s Division of Cancer Prevention has entered some 800 agents into a chemopreventive agent testing program. Two critical steps involve: 1) in vitro/in vivo morphologic assays and 2) animal tumor assays (incidence/multiplicity reduction). We sought to determine how accurately the earlier-stage (morphologic) assays predict efficacy in the later-stage (animal tumor) assays.