tbuckley/cabot-search huggingface dataset:
Hospital revises its own data in government league table
Authors: M M Wright
Journal: BMJ (2002)

EDITOR—The government has placed great emphasis on hospital league tables, although potential and real flaws have been identified. We therefore thought it was appropriate to review our hospital's process, assessing the accuracy of the mortality data in general surgery and the quality of patient care.

The data submitted included several patients who had undergone procedures that were specifically excluded. In the non-emergency group this would have reduced the number of patient deaths from …
Genome-wide copy number analyses identified novel cancer genes in hepatocellular carcinoma
Authors: Deshui Jia, Lin Wei, Weijie Guo, Ruopeng Zha, Meiyan Bao, Zhiao Chen, Yingjun Zhao, Chao Ge, Fangyu Zhao, Taoyang Chen, Ming Yao, Jinjun Li, Hongyang Wang, Jianren Gu, Xianghuo He
Journal: Hepatology (2011)

A powerful way to identify driver genes with causal roles in carcinogenesis is to detect genomic regions that undergo frequent alterations in cancers. Here we identified 1,241 regions of somatic copy number alterations in 58 paired hepatocellular carcinoma (HCC) tumors and adjacent nontumor tissues using genome-wide single nucleotide polymorphism (SNP) 6.0 arrays. Subsequently, by integrating copy number profiles with gene expression signatures derived from the same HCC patients, we identified 362 differentially expressed genes within the aberrant regions. Among these, 20 candidate genes were chosen for further functional assessments. One novel tumor suppressor (tripartite motif-containing 35 [TRIM35]) and two putative oncogenes (hairy/enhancer-of-split related with YRPW motif 1 [HEY1] and small nuclear ribonucleoprotein polypeptide E [SNRPE]) were discovered by various in vitro and in vivo tumorigenicity experiments. Importantly, it was demonstrated that decreases of TRIM35 expression are a frequent event in HCC and the expression level of TRIM35 was negatively correlated with tumor size, histological grade, and serum alpha-fetoprotein concentration.These results showed that integration of genomic and transcriptional data offers powerful potential for identifying novel cancer genes in HCC pathogenesis.
Informed reasoning: repositioning of nitisinone to treat oculocutaneous albinism
Authors: Prashiela Manga, Seth J. Orlow
Journal: Journal of Clinical Investigation (2011)

Oculocutaneous albinism (OCA) is a group of genetic disorders characterized by hypopigmentation of the skin, hair, and eyes. Affected individuals experience reduced visual acuity and substantially increased skin cancer risk. There are four major types of OCA (OCA1–OCA4) that result from disruption in production of melanin from tyrosine. Current treatment options for individuals with OCA are limited to attempts to correct visual problems and counseling to promote use of sun protective measures. However, Onojafe et al., reporting in this issue of the JCI, provide hope for a new treatment approach for OCA, as they demonstrate that treating mice that model OCA-1b with nitisinone, which is FDA approved for treating hereditary tyrosinemia type 1, elevates plasma tyrosine levels, and increases eye and hair pigmentation.
In Vivo-In Vitro Correlation of Myelotoxicity of 9-Methoxypyrazoloacridine [NSC-366140, PD115934] to Myeloid and Erythroid Hematopoietic Progenitors From Human, Murine, and Canine Marrow
Authors: R. E. Parchment, D. A. Volpe, P. M. LoRusso, C. L. Erickson-Miller, M. J. Murphy, C. K. Grieshaber
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article In Vivo-In Vitro Correlation of Myelotoxicity of 9-Methoxypyrazoloacridine [NSC-366140, PD115934] to Myeloid and Erythroid Hematopoietic Progenitors From Human, Murine, and Canine Marrow Get access Ralph E. Parchment, Ralph E. Parchment Search for other works by this author on: Oxford Academic PubMed Google Scholar Donna A. Volpe, Donna A. Volpe Search for other works by this author on: Oxford Academic PubMed Google Scholar Patricia M. LoRusso, Patricia M. LoRusso Search for other works by this author on: Oxford Academic PubMed Google Scholar Connie L. Erickson-Miller, Connie L. Erickson-Miller Search for other works by this author on: Oxford Academic PubMed Google Scholar Martin J. Murphy, Jr., Martin J. Murphy, Jr. Search for other works by this author on: Oxford Academic PubMed Google Scholar Charles K. Grieshaber Charles K. Grieshaber * * Correspondence to : Ralph E. Parchment, Ph.D., DRT⊘ORR⊘CDER, Food and Drug Administration, Mod-1. Rm. 2023, 8301 Muirkirk Rd., Laurel, MD 20708 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 4, 16 February 1994, Pages 273–280, https://doi.org/10.1093/jnci/86.4.273 Published: 16 February 1994 Article history Received: 02 August 1993 Revision received: 10 November 1993 Accepted: 22 November 1993 Published: 16 February 1994
Cardiovascular fitness and thermoregulation during prolonged exercise in man.
Authors: P L Greenhaff
Journal: British Journal of Sports Medicine (1989)

Nine healthy male subjects differing in their training status (VO2 max 54 +/- 7 ml.min-1.kg-1, mean +/- SD; 43-64 ml.min-1 kg-1, range) exercised on two occasions separated by one week. On each occasion, having fasted overnight, subjects exercised for 1 h on an electrically braked cycle ergometer at a workload equivalent to 70 per cent VO2 max (test A) or at a fixed workload of 140 W (test B). Each test was assigned in a randomized manner and was performed at an ambient temperature of 22.5 +/- 0.0 degrees C and a relative humidity of 85 +/- 0 per cent. Absolute exercise workload was the most successful predictor of sweat loss during test A (r = 0.82, p less than 0.01). Sweat loss was also related to VO2 max tests A (r = 0.67, p less than 0.05) and B (r = 0.67, p less than 0.05). There was no relationship between resting pre-exercise core temperature and VO2 max. However, core temperature recorded during the final min of exercise in test B was inversely related to VO2 max (r = -0.86, p less than 0.01). As a consequence, core temperature during the final minute of exercise was also related to the relative exercise intensity (% VO2 max) performed (r = 0.82, p less than 0.01). The heart rate response during test B was inversely related to VO2 max (r = -0.71, p less than 0.05) and was positively related to the relative exercise intensity performed (r = 0.68, p less than 0.05). No relationship was found between weighted mean skin temperature during the final minute of exercise and the relative (r = 0.26) or absolute (r = 0.03) workloads performed during exercise. The results of the present experiment suggest that cardiovascular fitness (as indicated by VO2 max) will have a significant influence upon the thermoregulatory responses of Man during exercise.
Human tissue-type plasminogen activator releases fibrinopeptides A and B from fibrinogen.
Authors: J I Weitz, M K Cruickshank, B Thong, B Leslie, M N Levine, J Ginsberg, T Eckhardt
Journal: Journal of Clinical Investigation (1988)

In five patients with venous thromboembolic disease treated with recombinant tissue-type plasminogen activator (rt-PA), there was a marked increase in the mean concentrations of fibrinopeptide A (from 0.6 to 5.9 nM; P less than 0.0001) and desarginine fibrinopeptide B (from 5.6 nM to 24.1 nM; P less than 0.01) 30 min after a bolus of rt-PA (0.6 mg/kg). Thrombin was unlikely to be responsible because the levels of desarginine fibrinopeptide B exceeded those of fibrinopeptide A and the changes occurred despite concomitant heparin therapy. The purpose of this study therefore, was to determine whether rt-PA directly releases the fibrinopeptides from fibrinogen. Incubation of rt-PA with heparinized plasma or purified fibrinogen resulted in time and dose-dependent release of both fibrinopeptide A and B. Contaminating thrombin was not responsible for this activity by the following criteria: the rate of rt-PA mediated fibrinopeptide B release was considerably faster than that of fibrinopeptide A, and fibrinopeptide release was unaffected by heparin, hirudin, or a monospecific antithrombin IgG. Aprotinin also had no effect on fibrinopeptide release, indicating that this activity was not plasmin mediated. Fibrinopeptide release was shown to be due to rt-PA because this activity was completely blocked by a monoclonal antibody against the enzyme. Further, the specificity of rt-PA for the thrombin cleavage sites on fibrinogen was confirmed by the demonstration that rt-PA released fibrinopeptide A or fibrinopeptide B from fibrinopeptide A or B-containing substrates, respectively. These studies thus demonstrate that (a) rt-PA releases fibrinopeptides A and B from fibrinogen thereby indicating that this enzyme is not specific for plasminogen, and (b) plasma fibrinopeptide A and desarginine fibrinopeptide B levels are not specific markers of thrombin action on fibrinogen in patients receiving rt-PA.
INTRA-AORTIC BALLOON PUMP DOES NOT IMPROVE SURVIVAL IN PATIENTS WITH ST SEGMENT ELEVATION MYOCARDIAL INFARCTION COMPLICATED BY CARDIOGENIC SHOCK: DATA FROM A LARGE SINGLE CENTER REGISTRY
Authors: Gaetano M. De Ferrari, Stefano Cornara, Alberto Somaschini, Raniero Covi, Andrea Baldo, Rita Camporotondo, Gabriele Crimi, Marco Ferlini, Silvia Pica, Maurizio Ferrario
Journal: Journal of the American College of Cardiology (2015)
Thrombin overcomes the thrombosis defect associated with platelet GPVI/FcRγ deficiency
Authors: Pierre Mangin, Cindy L. Yap, Christelle Nonne, Sharelle A. Sturgeon, Isaac Goncalves, Yuping Yuan, Simone M. Schoenwaelder, Christine E. Wright, Francois Lanza, Shaun P. Jackson
Journal: Blood (2006)
Hyperosmolar Diabetic Coma— Ketotic and Nonketotic
Authors: Sidney Sament
Journal: JAMA (1974)

To the Editor.—  The editorial (227:317, 1974) rightly stated that ketoacidosis is not the only factor in the production of diabetic coma. Dehydration and consequent hyperosmolarity are important considerations. As coauthor of the article of reference,1I would like to add further observations.  In my own experience with the different types of diabetic coma, I have found that the ketotic type of coma is the more severe, requires more insulin, and often has a worse prognosis than that of the nonketotic type. I think there is a direct correlation between the bedside evaluation of the severity of the ketosis (acidotic breathing, ketones in urine and blood) and the severity of coma. Ketosis does, in fact, directly produce coma, and of a greater severity than that due to hyperglycemia and dehydration.  The poor correlation between the blood pH and severity of coma that you mention is supported by the observation
Failure of ornithine decarboxylase inhibition to alter small intestinal epithelial repair after transient segmental ischaemia.
Authors: C Guzman, R J MacLeod, J R Hamilton
Journal: Gut (1988)

To evaluate the roles of ornithine decarboxylase (ODC) and polyamines in the regulation of epithelial repair, rabbit mid-small intestine after transient ischaemic villus injury in the presence and absence of DL-difluoromethylornithine (DFMO), an irreversible inhibitor of ODC was studied. Rabbits received 2% (w/v) DFMO in drinking water for two days before undergoing a sham laparotomy, or a 90 minute mesenteric vascular occlusion of 20 cm of mid-intestine. DFMO fed and control rabbits were studied four, 24, 72, or 120 hours after this ischaemic intestinal injury. In controls, ischaemic injury caused shortened villi at four hours (p less than 0.01), diminished mucosal sucrase and alkaline phosphatase activities at 24 hours (p less than 0.05), but raised ODC (p less than 0.001) and thymidine kinase (p less than 0.01) activities at four hours with recovery by 72 hours. DFMO treatment significantly reduced ODC activity at all stages of the experiment and significantly inhibited the rise in activity observed after injury (p less than 0.01). Mucosal concentrations of the polyamines, spermidine and spermine, were similar in the sham operated groups; four hours and 24 hours after ischaemia, they increased in the DFMO animals (p less than 0.01) but fell (p less than 0.05) in those that did not receive DFMO. After ischaemic injury, DFMO treatment inhibited ODC but failed to influence recovery of villus structure or enzyme activities in the small intestine. We conclude that ODC and the polyamines, spermidine and spermine, are not key regulators of small intestinal repair after transient ischaemia.
Giant Basilar-Artery Aneurysm
Authors: Ammar M Killu, Giuseppe Lanzino
Journal: New England Journal of Medicine (2012)

A 46-year-old right-handed woman presented with a 3-month history of occipital headache, progressive confusion, and personality change. Neurologic examination revealed mildly impaired smooth-pursuit eye movements, mildly impaired walking with a tandem gait, and a score of 30 out of 38 on the Kokmen Short Test of Mental Status (with a score of less than or equal to 29 indicating dementia). Computed tomography of the head revealed a circumferential midbrain lesion with mass effect and hydrocephalus. Magnetic resonance imaging (MRI) and magnetic resonance angiography revealed an aneurysm (3.5 cm by 4 cm) (Panel A, arrowheads; the inset indicates the imaging plane) . . .
Deficiency of CD73/ecto-5′-nucleotidase in mice enhances acute graft-versus-host disease
Authors: Hiroki Tsukamoto, Petya Chernogorova, Korcan Ayata, Ulrike V. Gerlach, Ankur Rughani, Jerry W. Ritchey, Jayanthi Ganesan, Marie Follo, Robert Zeiser, Linda F. Thompson, Marco Idzko
Journal: Blood (2012)
Committed mast cell progenitors in mouse blood differ in maturity between <scp>T</scp>h1 and <scp>T</scp>h2 strains
Authors: J. S. Dahlin, B. Heyman, J. Hallgren
Journal: Allergy (2013)

Mast cell progenitors (MCp) leave the bone marrow and migrate to peripheral tissues where they mature. Although the existence of committed MCp in adult mouse and human blood has been postulated, they have never been found. We have isolated a rare population of cells in adult mouse blood, committed to the mast cell lineage. These were identified as lineage- c-kit(hi) ST2+ integrin β7(hi) CD16/32(hi) cells. Moreover, a major difference in maturity of these cells based on FcεRI expression was observed between the Th2-prone BALB/c strain and the Th1-prone C57BL/6 strain (66% vs. 25% FcεRI+, respectively). Therefore, the choice of mouse strain is critical when studying disease models such as experimental asthma where mast cells and their progenitors are involved.
Inflammation and platelet-activating factor production during hepatic ischemia/reperfusion
Authors: Weiguo Zhou, Mark O. McCollum, Barry A. Levine, Merle S. Olson
Journal: Hepatology (1992)

The role of platelet-activating factor as a potential mediator of hepatic inflammatory injury associated with liver ischemia/reperfusion was investigated using a partial no-flow model in rats in vivo. Platelet-activating factor levels of livers from sham-operated rats and from animals experiencing hepatic reperfusion for less than 6 hr were very low. They were observed to increase significantly after 12 hr of reperfusion and reached peak levels after a 24-hr reperfusion period, a time when maximal hepatic injury and inflammation occurred. Treatment of experimental rats with WEB2170, a platelet-activating factor receptor antagonist, attenuated the hepatic injury and inflammation, as evidenced by decreases in plasma ALT and in hepatocyte necrosis and neutrophil infiltration. Both inactivation of Kupffer cells with gadolinium chloride and inhibition of the formation of reactive oxygen species with allopurinol reduced platelet-activating factor production in the liver, whereas induction of neutropenia had no effect, suggesting that interaction of Kupffer cells with oxygen-derived free radicals may be a plausible mechanism for hepatic platelet-activating factor accumulation. It is concluded that platelet-activating factor contributes to the inflammatory consequences of ischemia/reperfusion underlying late-phase hepatic injury.
Grant's Method of Anatomy by Regions Descriptive and Deductive
Authors: Charles Clayman
Journal: JAMA (1980)

For more than 40 years, this text has been employed by students of anatomy. The concept of regionalization employing logical deduction initiated by the late Professor Grant remains as viable today as the day of publication of the first edition. The full text has been condensed 10%, notwithstanding "cautious" introduction of new text and illustrations. The reader's concentration is often jarred by the need to shift many pages to relate an illustration to the text. This is difficult to remedy and is another reason why a more encyclopedic text or atlas should be used in conjunction with<i>Grant's Method</i>. The 30 radiographs suffer in reproduction—they often appear to be overexposed and provide little, aside from affording a freshman medical student the novelty of viewing a picture of an x-ray film. The text is suitable for the clinician who wishes to correlate his hazy recollections of anatomy with a current clinical
Normalization of Naxos plakoglobin levels restores cardiac function in mice
Authors: Zhiwei Zhang, Matthew J. Stroud, Jianlin Zhang, Xi Fang, Kunfu Ouyang, Kensuke Kimura, Yongxin Mu, Nancy D. Dalton, Yusu Gu, William H. Bradford, Kirk L. Peterson, Hongqiang Cheng, Xinmin Zhou, Ju Chen
Journal: Journal of Clinical Investigation (2015)

Arrhythmogenic cardiomyopathy (AC) is associated with mutations in genes encoding intercalated disc proteins and ultimately results in sudden cardiac death. A subset of patients with AC have the autosomal recessive cardiocutaneous disorder Naxos disease, which is caused by a 2-base pair deletion in the plakoglobin-encoding gene JUP that results in a truncated protein with reduced expression. In mice, cardiomyocyte-specific plakoglobin deficiency recapitulates many aspects of human AC, and overexpression of the truncated Naxos-associated plakoglobin also results in an AC-like phenotype; therefore, it is unclear whether Naxos disease results from loss or gain of function consequent to the plakoglobin mutation. Here, we generated 2 knockin mouse models in which endogenous Jup was engineered to express the Naxos-associated form of plakoglobin. In one model, Naxos plakoglobin bypassed the nonsense-mediated mRNA decay pathway, resulting in normal levels of the truncated plakoglobin. Moreover, restoration of Naxos plakoglobin to WT levels resulted in normal heart function. Together, these data indicate that a gain of function in the truncated form of the protein does not underlie the clinical phenotype of patients with Naxos disease and instead suggest that insufficiency of the truncated Naxos plakoglobin accounts for disease manifestation. Moreover, these results suggest that increasing levels of truncated or WT plakoglobin has potential as a therapeutic approach to Naxos disease.
Randomized, Double-Blind, Placebo-Controlled Study of Sitaxsentan to Improve Impaired Exercise Tolerance in Patients With Heart Failure and a Preserved Ejection Fraction
Authors: Michael R. Zile, Robert C. Bourge, Margaret M. Redfield, Duo Zhou, Catalin F. Baicu, William C. Little
Journal: JACC Heart Failure (2014)

The purpose of this study was to evaluate the efficacy and safety of the selective endothelin type A (ETA) receptor antagonist sitaxsentan in patients who have heart failure with preserved ejection fraction (HFpEF).Fifty percent of heart failure (HF) patients have a preserved ejection fraction. No treatment has been shown to improve their clinical outcomes. Previous studies have suggested that ETA receptor antagonists might improve diastolic function and exercise tolerance in some forms of HF.In all, 192 HFpEF patients (EF ≥50%) were randomly assigned 2:1 to sitaxsentan 100 mg/day (n = 128) versus placebo (n = 64) for 24 weeks. The primary endpoint was change in treadmill exercise time after 24 weeks of treatment. Secondary objectives included changes in left ventricular mass, transmitral inflow velocity to early diastolic mitral annulus velocity ratio, and Minnesota Living With Heart Failure questionnaire, and New York Heart Association functional class. Subjects were age 65 ± 11 years, 63% female, 29% non-Caucasian, and in functional class II (56.5%) or III (43.5%).Subjects treated with sitaxsentan had an increase in median treadmill time (90 s) compared with placebo-treated subjects (37 s, p = 0.0302). There was no significant treatment differences in transmitral inflow velocity to early diastolic mitral annulus velocity ratio, left ventricular mass, Minnesota Living With Heart Failure questionnaire, New York Heart Association functional class, deaths, or HF hospital stay. The incidence of adverse events was similar for sitaxsentan and placebo.In HFpEF patients, treatment with a selective ETA receptor antagonist increased exercise tolerance but did not improve any of the secondary endpoints such as left ventricular mass or diastolic function. Further studies will be necessary to determine whether ETA receptor antagonists may be useful in the treatment of HFpEF. (A Study of the Effectiveness of Sitaxsentan Sodium in Patients With Diastolic Heart Failure; NCT00303498).
Improvement of Diabetic Control and Acceptability of a Three-Injection Insulin Regimen in Diabetic Adolescents: A multicenter controlled study
Authors: P F Bougnères, P Landais, A M Mairesse, J P Jais, J Jos, J Peyraud, M C Wieliczko, P Chavoix, P Garandeau, D Asensi, H Ythier, V Rouland, T Mazoyer, F Leturcq, E Raynaud
Journal: Diabetes Care (1993)

Objective— To compare the effectiveness and acceptability of a three-injection insulin regimen with the conventional two-injection therapy in an unselected population of diabetic adolescents. Research Design and Methods— Some 205 patients aged 10–18 yr with IDDM, who were previously treated with two daily insulin injections, were included without any selection into a randomized trial. They were either switched to three (regular prebreakfast, regular prelunch, and [regular + ultralente] predinner) or remained on two ([regular + intermediary] prebreakfast and predinner) subcutaneous injections. They were evaluated after 1 yr of treatment. The major criteria of outcome of efficacy were the concentration of GHb, the frequency of severe hypoglycemia and DKA, and body weight. Results— Of the patients, 82% accepted the three-injection regimen, and 83% accepted the two-injection regimen. At entry into the trial, no significant differences appeared between the two treatment groups nor among patients refusing the allocated regimen. Significant explanatory variables predicting initial diabetes control were duration of disease and adherence to diet. GHb, decreased from 9.8 ± 0.1 to 9.3 ± 0.2% (P &amp;lt; 0.05) in the three-injection group, whereas it increased from 9.5 ± 0.3 to 9.8 ± 0.3% (P &amp;lt; 0.05) in the two-injection group, resulting in a modest (0.75%) but significant difference (P &amp;lt; 0.05) between GHb change in the two groups. The difference reached 1.4% (P &amp;lt; 0.0002) in patients with GHb &amp;gt; 11.2% at entry. The frequency of hypoglycemia and DKA was similar in the two groups. None of the parameters known to potentially influence glycemic control changed during the trial, and, therefore, the improvement of GHb could be attributed to the pattern of daily insulin distribution per se. Conclusions— In the general diabetic adolescent population, the efficacy of a three-injection regimen is somewhat superior to that of a conventional two-injection regimen, particularly in patients previously poorly controlled. The acceptability of this regimen being excellent, its increased use should be considered in this age-group.