tbuckley/cabot-search huggingface dataset:
Does Coronary Artery Bypass Grafting Alone Correct Moderate Ischemic Mitral Regurgitation?
Authors: Lishan Aklog, Farzan Filsoufi, Kathryn Q. Flores, Raymond H. Chen, Lawrence H. Cohn, Nadia S. Nathan, John G. Byrne, David H. Adams
Journal: Circulation (2001)

The optimal management of moderate (3+ on a scale of 0 to 4+) ischemic mitral regurgitation (MR) remains controversial. Some advocate CABG alone, whereas others favor concomitant mitral annuloplasty. To clarify the optimal management of these patients, we evaluated the early impact of isolated CABG on moderate ischemic MR.Between January 1992 and August 1999, 136 patients (54% male, mean age 70.5 years, mean New York Heart Association class 2.7, mean ejection fraction 38.1%) with a preoperative diagnosis of moderate ischemic MR, without leaflet prolapse or pathology, underwent isolated CABG. Thirty-eight (28%) of 136 patients had intraoperative transesophageal echocardiography (TEE) before CABG, and 68 (50%) had postoperative transthoracic echocardiography (TTE) within 6 weeks of surgery. The subgroups of patients undergoing intraoperative TEE and postoperative TTE had preoperative characteristics similar to the overall group. The 30-day operative mortality was 2.9% (). Intraoperative TEE downgraded the severity of MR to mild or less (0 to 2+) in 89% (). On postoperative TTE, 40% () continued to have at least moderate MR (3 to 4+), 51% () improved somewhat to mild (2+) MR, and only 9% () had resolution of their MR (0 to 1+). The mean preoperative, intraoperative, and postoperative MR grades were 3.0+/-0.0, 1.4+/-1.0, and 2.3+/-0.8, respectively (P<0.001).CABG alone for moderate ischemic MR leaves many patients with significant residual MR and may not be the optimal therapy for most patients. Intraoperative TEE may significantly underestimate the severity of ischemic MR. A preoperative diagnosis of moderate MR may warrant concomitant mitral annuloplasty.
Primary central nervous system lymphoma in Japan: Changes in clinical features, treatment, and prognosis during 1985-2004
Authors: Yuta Shibamoto, Hiroyuki Ogino, Gen Suzuki, Mitsuhiro Takemoto, Norio Araki, Koichi Isobe, Emiko Tsuchida, Katsumasa Nakamura, Masahiro Kenjo, Kazunori Suzuki, Masako Hosono, Sunao Tokumaru, Shun-ichi Ishihara, Eriko Kato, Noriko Ii, Naofumi Hayabuchi
Journal: Neuro-Oncology (2008)

We have conducted nationwide surveys of primary central nervous system lymphoma (PCNSL) treated since 1985. In the present study, we newly collected data between 2000 and 2004 and investigated changes in clinical features and outcome over time. A total of 739 patients with histologically proven PCNSL under going radiotherapy were analyzed. Seventeen institutions were surveyed, and data on 131 patients were collected. These data were compared with updated data that were previously obtained for 466 patients treated during 1985-1994 and 142 patients treated during 1995-1999. Recent trends toward decrease in male/female ratio, increase in aged patients, and increase in patients with multiple lesions were seen. Regarding treatment, decrease in attempts at surgical tumor removal and increases in use of systemic chemotherapy and methotrexate (MTX)-containing regimens were observed. The median survival time was 18, 29, and 24 months for patients seen during 1985-1994, 1995-1999, and 2000-2004, respectively, and the respective 5-year survival rates were 15%, 30%, and 30%. In groups seen during 1995-1999 and during 2000-2004, patients who received systemic or MTX-containing chemotherapy had better prognosis than those who did not. Multivariate analysis of all patients seen during 1985-2004 suggested the usefulness of MTX-containing chemotherapy as well as the importance of age, lactate dehydrogenase level, and tumor multiplicity as prognostic factors. Thus, this study revealed several notable changes in clinical features of PCNSL patients. The prognosis improved during the last 10 years. Advantage of radiation plus chemotherapy, especially MTX-containing chemotherapy, over radiation alone was suggested.
Circulating Tumor Cells versus Imaging—Predicting Overall Survival in Metastatic Breast Cancer
Authors: G. Thomas Budd, Massimo Cristofanilli, Mathew J. Ellis, Allison Stopeck, Ernest Borden, M. Craig Miller, Jeri Matera, Madeline Repollet, Gerald V. Doyle, Leon W.M.M. Terstappen, Daniel F. Hayes
Journal: Clinical Cancer Research (2006)

The presence of >or=5 circulating tumor cells (CTC) in 7.5 mL blood from patients with measurable metastatic breast cancer before and/or after initiation of therapy is associated with shorter progression-free and overall survival. In this report, we compared the use of CTCs to radiology for prediction of overall survival.One hundred thirty-eight metastatic breast cancer patients had imaging studies done before and a median of 10 weeks after the initiation of therapy. All scans were centrally reviewed by two independent radiologists using WHO criteria to determine radiologic response. CTC counts were determined approximately 4 weeks after initiation of therapy. Specimens were analyzed at one of seven laboratories and reviewed by a central laboratory.Interreader variability for radiologic responses and CTC counts were 15.2% and 0.7%, respectively. The median overall survival of 13 (9%) patients with radiologic nonprogression and >or=5 CTCs was significantly shorter than that of the 83 (60%) patients with radiologic nonprogression and <5 CTCs (15.3 versus 26.9 months; P=0.0389). The median overall survival of the 20 (14%) patients with radiologic progression and <5 CTCs was significantly longer than the 22 (16%) patients with >or=5 CTCs that showed progression by radiology (19.9 versus 6.4 months; P=0.0039).Assessment of CTCs is an earlier, more reproducible indication of disease status than current imaging methods. CTCs may be a superior surrogate end point, as they are highly reproducible and correlate better with overall survival than do changes determined by traditional radiology.
Lung and chest wall mechanics in ventilated patients with end stage idiopathic pulmonary fibrosis
Authors: S. Nava, F. Rubini
Journal: Thorax (1999)

<h3>BACKGROUND</h3> Idiopathic pulmonary fibrosis is an inflammatory disease which leads to chronic ventilatory insufficiency and is characterised by a reduction in pulmonary static and dynamic volumes. It has been suggested that lung elastance may also be abnormally increased, particularly in end stage disease, but this has not been systematically tested. The aim of this study was to assess the respiratory mechanics during mechanical ventilation in patients affected by end stage disease. <h3>METHODS</h3> Respiratory mechanics were monitored in seven patients with idiopathic pulmonary fibrosis being ventilated for acute respiratory failure (Pao<sub>2</sub>/Fio<sub>2</sub> 5.8 (0.3); pH 7.28 (0.02); Paco<sub>2</sub> 8.44 (0.82) kPa; tidal volume 3.4 (0.2) ml/kg; respiratory rate 35.1 (8.8) breaths/min) using an oesophageal balloon and airway occlusion during constant flow inflation. The total respiratory system mechanics (rs) was partitioned into lung (L) and chest wall (w) mechanics to measure static intrinsic positive end expiratory pressure (PEEPi), static (Est) and dynamic (Edyn) elastances, total respiratory resistance (Rrs), interrupter respiratory resistance (Rint,rs), and additional respiratory resistance (ΔRrs). <h3>RESULTS</h3> PEEPi was negligible in all patients. Edyn,rs and Est,rs were markedly increased (60.9 (7.3) and 51.9 (8.0) cm H<sub>2</sub>O/l, respectively), and this was due to abnormal lung elastance (dynamic 53.9 (8.0) cm H<sub>2</sub>O/l, static 46.1 (8.1) cm H<sub>2</sub>O/l) while chest wall elastance was only slightly increased. Rrs and Rint,rs were also increased above the normal range (16.7 (4.5) and 13.7 (3.5) cm H<sub>2</sub>O/l/s, respectively). RL and Rint,L contributed 88% and 89%, on average, to the total. Edyn,rs, Est,rs, Rrs and Rint,rs were significantly correlated with the degree of hypercapnia (<i>r</i> = 0.64 (p&lt;0.01),<i>r</i> = 0.54 (p&lt;0.05),<i>r</i> = 0.84 (p&lt;0.001), and<i>r</i> = 0.72 (p&lt;0.001), respectively). <h3>CONCLUSIONS</h3> The elastances and resistances of the respiratory system are significantly altered in ventilated patients with end stage idiopathic pulmonary fibrosis. These features are almost totally due to abnormalities in lung mechanics. These profound alterations in elastic and resistive mechanical properties at this stage of the disease may be responsible for the onset of hypercapnia.
PWE-007 Paracrine prostaglandin-E signalling modulates canine gastric epithelial cell migration
Authors: R Hollins, A I Freeman, P J Cripps, A D Radford, P J M Noble
Journal: Gut (2012)

<h3>Introduction</h3> Gastric ulceration is a limiting complication of therapy with cyclooxygenase (COX) antagonists, widely used anti-inflammatory/analgesic drugs in both humans and dogs. COX-derived prostaglandin E (PGE) has an important role in gastric defense and cytoprotection via promotion of blood flow and mucus secretion and inhibition of gastric acid secretion. Given the importance of gastric epithelial cell migration in reestablishing epithelial integrity following gastric damage, we have investigated whether paracrine PGE signalling has a role in the modulation of gastric epithelial cell migration. <h3>Methods</h3> In order to retain paracrine signalling between different cell types, we isolated intact gastric glands via collagenase digestion of canine gastric mucosal tissue. Isolated glands spread in vitro to form islands of cells. The rate of gland spreading over 48h was measured as a surrogate for cell migration speed. Lamellipodia protrusion was analysed as an index of spreading activity. A value for lamellopodia area was calculated by measuring spread area minus area bounded by nuclei of cells at the edge of spread glands. Spread glands, when serum-starved, exhibit a reduction in area. We added both a selective and a non-selective COX antagonist and PGE<sub>2</sub> to serum-starved glands to assess their effects on migration. All treatments were added blindly to eliminate bias. Statistical significance was assessed using univariate analysis of variance. Expression of COX-2 and PGE receptors (EP-3 and EP-4) was assessed by RT-PCR and immunohistochemistry. <h3>Results</h3> RT-PCR confirmed COX-2, EP-3 and EP-4 expression in our samples. COX-2 immunoreactivity was present in the majority of gland cells. The COX 1/2 antagonist indomethacin (50 μM) decreased spreading (0.85-fold, p&lt;0.05, n=5–9 for all experiments) and lamellipodia area (0.3-fold, p&lt;0.05). The COX-2 selective antagonist NS-398 (10μM) caused similar decreases to indomethacin (0.8-fold and 0.65-fold respectively, p&lt;0.05). PGE (1μM) prevented a 0.7-fold reduction in island area elicited by incubation in serum free medium (p&lt;0.05). <h3>Conclusion</h3> This data shows a role for COX-2 derived PGE in the promotion of gastric cell migration and cellular lamellipodia formation. A reduction of mucosal PGE via COX-2 antagonism may therefore inhibit gastric epithelial cell migration contributing to COX-antagonist elicited gastric ulceration in both humans and dogs. <h3>Competing interests</h3> None declared.
CCL11–CCR3 Interactions Promote Survival of Anaplastic Large Cell Lymphoma Cells via ERK1/2 Activation
Authors: Tomomitsu Miyagaki, Makoto Sugaya, Takashi Murakami, Yoshihide Asano, Yayoi Tada, Takafumi Kadono, Hitoshi Okochi, Kunihiko Tamaki, Shinichi Sato
Journal: Cancer Research (2011)

Abstract CCR3 is a specific marker of anaplastic large cell lymphoma (ALCL) cells. ALCL cells also express CCL11, a ligand for CCR3, leading to the hypothesis that CCL11 may play an autocrine role in ALCL progression. In this study, we investigated a role of CCL11 in cell survival and growth of human Ki-JK cells, established from an ALCL patient, and murine EL-4 lymphoma cells. Both Ki-JK and EL-4 cells expressed cell surface CCR3. CCL11 increased cell survival rates of Ki-JK cells in a dose-dependent manner, whereas it promoted EL-4 cell proliferation. Furthermore, CCL11 induced phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 in both Ki-JK cells and EL-4 cells. Cell survival and tumor proliferation promoted by CCL11 was completely blocked by inhibition of ERK phosphorylation. CCL11 induced expression of antiapoptotic proteins, Bcl-xL and survivin, in Ki-JK cells. CCL11 also enhanced tumor growth of EL-4 and Ki-JK cells in vivo. Consistent with these results, tumor cells of cutaneous ALCL expressed CCR3 and increased levels of phosphorylated ERK1/2, Bcl-xL, and survivin in situ. Thus, our findings prompt a novel therapeutic approach to treat relapses of an aggressive form of lymphoma based on the discovery that a cell surface marker of disease functions as a critical autocrine growth receptor. Cancer Res; 71(6); 2056–65. ©2011 AACR.
Malaria Immunity in Man and Mosquito: Insights into Unsolved Mysteries of a Deadly Infectious Disease
Authors: Peter D. Crompton, Jacqueline Moebius, Silvia Portugal, Michael Waisberg, Geoffrey Hart, Lindsey S. Garver, Louis H. Miller, Carolina Barillas-Mury, Susan K. Pierce
Journal: Annual Review of Immunology (2014)

Malaria is a mosquito-borne disease caused by parasites of the obligate intracellular Apicomplexa phylum the most deadly of which, Plasmodium falciparum, prevails in Africa. Malaria imposes a huge health burden on the world's most vulnerable populations, claiming the lives of nearly one million children and pregnant women each year. Although there is keen interest in eradicating malaria, we do not yet have the necessary tools to meet this challenge, including an effective malaria vaccine and adequate vector control strategies. Here we review what is known about the mechanisms at play in immune resistance to malaria in both the human and mosquito hosts at each step in the parasite's complex life cycle with a view toward developing the tools that will contribute to the prevention of disease and death and, ultimately, to the goal of malaria eradication. In so doing, we hope to inspire immunologists to participate in defeating this devastating disease.
Hand warming as a treatment for Raynaud's phenomenon in systemic sclerosis
Authors: M.J.D. GOODFIELD, N.R. ROWELL
Journal: British Journal of Dermatology (1988)

Twelve patients with Raynaud's phenomenon (RP) due to systemic sclerosis (SS) warmed their hands for 5 min in hand hot water every 4 h throughout the day during alternate weeks of a 6-week study. There was a statistically significant decrease in the number and duration of Raynaud's attacks in the weeks in which warming was performed compared with the intervening weeks. An increase in blood flow as measured by laser-Doppler flowmetry accompanied clinical improvement. Simple hand warming appears to be effective in the management of RP in patients with SS.
Increase in extrapulmonary tuberculosis in England and Wales 1999-2006
Authors: M E Kruijshaar, I Abubakar
Journal: Thorax (2009)

<h3>Background:</h3> Extrapulmonary tuberculosis appears to be increasing in England and Wales. The trends in extrapulmonary tuberculosis and factors associated with these trends were examined. <h3>Methods:</h3> National tuberculosis surveillance data from 1999–2006 for England and Wales were used, including demographic, clinical and laboratory information. Trends in the proportion of tuberculosis cases with extrapulmonary disease were investigated using the χ<sup>2</sup> trend test and associated factors using logistic regression. <h3>Results:</h3> Among all the cases of tuberculosis, the proportion with extrapulmonary disease increased from 48% in 1999 (2717 cases) to 53% in 2006 (4205 cases, p&lt;0.001). Regression analysis showed that the rise in extrapulmonary disease was associated with an increase in the proportion of non-UK born cases (odds ratio 2.7, 95% CI 2.6 to 2.8). A more than threefold increase was observed in the proportion of all tuberculosis cases with miliary tuberculosis from 0.7% of all cases (38 cases) to 2.2% (180 cases, p&lt;0.001). This rise was not associated with changes in place of birth or in any of the other risk factors identified. <h3>Conclusions:</h3> The proportion of cases with extrapulmonary disease has increased over the study period. To a large extent this is due to an increasing proportion of non-UK born cases. Reasons for the rise in miliary tuberculosis require further investigation. Clinicians should have a higher index of clinical suspicion of extrapulmonary tuberculosis in non-UK born cases.
TOXIC PSYCHOSIS WITH TRANSIENT DYSMNESTIC SYNDROME FOLLOWING WITHDRAWAL FROM VALIUM
Authors: HARVEY H. BARTEN
Journal: American Journal of Psychiatry (1965)

The psychosis which follows barbiturate withdrawal(2) is also often heralded by a grand-mal seizure. The delirium begins on about the third day, and includes agitation and hallucinations. Mayer-Gross(2) states that a dysmnestic syndrome following a delirium is not rare, usually occurs when consciousness is clear but that the delirium can recur at night. "Eventual recovery is almost invariable." Of interest is the fact that the patient reported hallucinations in four different sensory modalities.
Coexisting metastatic neuroblastoma and dermal erythropoiesis in a blueberry muffin baby
Authors: Yi-Ling Shih, Tseng-tong Kuo, Yi-Hao Weng, Fang-Wen Tseng, Jing-Yi Lin, Hsin-Chun Ho, Ya-Ching Chang
Journal: Journal of the American Academy of Dermatology (2011)
Critical role for CXCR2 and CXCR2 ligands during the pathogenesis of ventilator-induced lung injury
Authors: John A. Belperio, Michael P. Keane, Marie D. Burdick, Vedang Londhe, Ying Ying Xue, Kewang Li, Roderick J. Phillips, Robert M. Strieter
Journal: Journal of Clinical Investigation (2002)

Mortality related to adult respiratory distress syndrome (ARDS) ranges from 35% to 65%. Lung-protective ventilator strategies can reduce mortality during ARDS. The protective strategies limit tidal volumes and peak pressures while maximizing positive end-expiratory pressure. The efficacy of this approach is due to a reduction of shear-stress of the lung and release of inflammatory mediators. Ventilator-induced lung injury (VILI) is characterized by inflammation. The specific mechanism(s) that recruit leukocytes during VILI have not been elucidated. Because the murine CXC chemokines KC/CXCL1 and MIP-2/CXCL2/3, via CXCR2, are potent neutrophil chemoattractants, we investigated their role in a murine model of VILI. We compared two ventilator strategies in C57BL/6 mice: high peak pressure and high stretch (high peak pressure/stretch) versus low peak pressure/stretch for 6 hours. Lung injury and neutrophil sequestration from the high–peak pressure/stretch group were greater than those from the low–peak pressure/stretch group. In addition, lung expression of KC/CXCL1 and MIP-2/CXCL2/3 paralleled lung injury and neutrophil sequestration. Moreover, in vivo inhibition of CXCR2/CXC chemokine ligand interactions led to a marked reduction in neutrophil sequestration and lung injury. These findings were confirmed using CXCR2–/– mice. Together these experiments support the notion that increased expression of KC/CXCL1 and MIP-2/CXCL2/3 and their interaction with CXCR2 are important in the pathogeneses of VILI.
Stronger Association between Obesity and Biochemical Progression after Radical Prostatectomy among Men Treated in the Last 10 Years
Authors: Stephen J. Freedland, William B. Isaacs, Leslie A. Mangold, Sindy K. Yiu, Kelly A. Grubb, Alan W. Partin, Jonathan I. Epstein, Patrick C. Walsh, Elizabeth A. Platz
Journal: Clinical Cancer Research (2005)

Abstract Background: Prior prospective cohort studies found that obesity was associated with increased risk of prostate cancer death. However, in the last 20 years dramatic changes in both the extent of obesity and prostate cancer screening and treatment have occurred. Whether the association between obesity and aggressive disease has changed as a result of these temporal changes is unclear. Methods: The study population consisted of 2,832 men treated by anatomic radical retropubic prostatectomy between 1985 and 2004 by a single surgeon. We evaluated the associations of obesity (body mass index ≥30 kg/m2)with tumor stage and grade using logistic regression and with biochemical progression using Cox proportional hazards regression. We examined whether these associations have changed over the last 20 years. Results: On multivariable analysis, the strength of the positive association between obesity and high-grade disease increased over time whereas the strength of the positive association between obesity and positive surgical margins decreased over time. The strength of the positive association between obesity and extraprostatic extension fluctuated over time, although the strongest and only statistically significant association was among men treated since 2000. The association between obesity and biochemical progression was strongest among men treated since 1995 (relative risk, 1.90; 95% confidence interval, 1.09-3.30; P = 0.02). Conclusions: In the current study, with the exception of positive surgical margins, the positive association between obesity and high-grade disease, advanced stage, and biochemical progression after radical retropubic prostatectomy was in general strongest among men treated in the last 10 years. The reasons for these findings are not clear, although factors possibly related to prostate-specific antigen–based screening and/or other temporal changes in prostate cancer diagnosis and treatment may play a role.
Two hepatic cytoplasmic protein fractions, Y and Z, and their possible role in the hepatic uptake of bilirubin, sulfobromophthalein, and other anions
Authors: A. J. Levi, I. M. Arias
Journal: Journal of Clinical Investigation (1969)

Two hepatic cytoplasmic protein fractions, designated Y and Z, which bind sulfobromophthalein (BSP), bilirubin, and other organic anions, have been separated by G75 Sephadex gel filtration. The physiologic role of these protein fractions has been investigated. They are present in the 110,000 g supernatant fraction from the livers of all the species tested (rats, mice, guinea pigs, Rhesus monkeys, sheep, and man). Tissues which do not preferentially extract BSP or bilirubin from plasma do not contain these fractions, with the exception of small intestinal mucosa which contains Z. Anion binding by Y and Z fractions is not due to contamination with albumin. These fractions are responsible for the cytoplasmic localization of bilirubin in Gunn rats, and the fractions bind bilirubin, BSP, or indocyanine green (ICG), whether given in vivo or added in vitro to liver supernate from normal rats. Flavaspidic acid-N-methylglucaminate, bunamiodyl, and iodipamide, drugs known to interfere with the hepatic uptake mechanism, compete with bilirubin and BSP for binding to Z. These proteins appear to be important in the transfer of organic anions from plasma into the liver and provide a tool for the investigation of hepatic uptake mechanisms.