tbuckley/cabot-search huggingface dataset:
Diaphragmatic movement in hemiplegic patients measured by ultrasonography.
Authors: E Cohen, A Mier, P Heywood, K Murphy, J Boultbee, A Guz
Journal: Thorax (1994)

BACKGROUND--It is known that automatic breathing is controlled by centres in the lower brain stem, whereas volitional breathing is controlled by the cerebral cortical centres. In hemiplegia, lesions above the brain stem result in paralysis of limb muscles. This study was performed to determine whether the diaphragm might also be affected in patients with hemiplegia. METHODS--Studies were performed in six normal control subjects and in eight patients with complete hemiplegia caused by a lesion above the brain stem, all with no known chest disease. Full lung function tests were performed. Diaphragmatic excursion and inspired volume (VT) were measured simultaneously by M mode ultrasonography and respiratory airflow measurements. Recordings of diaphragmatic excursion were performed on each side separately during volitional and automatic breathing at a similar range of VT. RESULTS--Lung function tests lay within the normal range in all the control subjects. In the hemiplegic patients mean (SD) vital capacity was 79 (18)% and residual volume was 123(30)% of predicted. Total lung capacity and functional residual capacity were in the normal range. In the control subjects no significant difference in diaphragmatic excursion was found between volitional and automatic breathing for the same range of inspired volume. By contrast, there was a significant decrease in diaphragmatic excursion during volitional breathing compared with automatic breathing on the affected side in four of the eight hemiplegic patients. CONCLUSIONS--In four of eight hemiplegic patients reduced diaphragmatic movement was present on the paralysed side during volitional inspiration when compared with automatic inspiration. The hemidiaphragm may be involved on the affected side in patients with hemiplegia.
Pim Kinase Inhibitors Sensitize Prostate Cancer Cells to Apoptosis Triggered by Bcl-2 Family Inhibitor ABT-737
Authors: Jin H. Song, Andrew S. Kraft
Journal: Cancer Research (2011)

Pim serine/threonine kinases contribute to prostate tumorigenesis and therapeutic resistance, yet Pim kinase inhibitors seem to have only limited effects on prostate cancer cell survival. Because overexpression of Bcl-2 family members are implicated in chemotherapeutic resistance in prostate cancer, we investigated the cooperative effects of Pim kinase inhibition with ABT-737, a small molecule antagonist of Bcl-2 family members. Strikingly, the addition of ABT-737 to Pim inhibitors triggered a robust apoptosis of prostate cancer cells in vitro and in vivo. Pim inhibitors decreased levels of the Bcl-2 family member Mcl-1, both by blocking 5'-cap dependent translation and decreasing protein half life. In addition, Pim inhibition transcriptionally increased levels of the BH3 protein Noxa by activating the unfolded protein response (UPR), lead to eIF-2α phosphorylation and increased expression of CHOP. Increased levels of Noxa also inactivated the remaining levels of Mcl-1 protein activity. Notably, these specific protein changes were essential to the apoptotic process because ABT-737 did not inhibit Mcl-1 protein activity and Mcl-1 overexpression blocked the apoptotic activity of ABT-737. Our results therefore suggest that this combination treatment could be developed as a potential therapy for human prostate cancer where overexpression of Pim kinases and antiapoptotic Bcl-2 family members drives tumor cell resistance to current anticancer therapies.
Comparison of Intravascular Ultrasound and Quantitative Coronary Angiography for the Assessment of Coronary Artery Disease Progression
Authors: Colin Berry, Philippe L. L’Allier, Jean Grégoire, Jacques Lespérance, Sylvie Levesque, Reda Ibrahim, Jean-Claude Tardif
Journal: Circulation (2007)

Background— The relative merits of quantitative coronary analysis (QCA) and intravascular ultrasound (IVUS) for the assessment of progression/regression in coronary artery disease are uncertain. To explore this subject further, we analyzed the angiographic and IVUS data derived from a contemporary clinical trial population. Methods and Results— We investigated the relationships between QCA and IVUS at single time points (n=525) and also for the changes over time (n=432). QCA and IVUS data underwent central laboratory analyses. Statistically significant correlations were observed between the QCA coronary artery score and the IVUS-derived lumen volume ( r =0.65, P &lt;0.0001) and total vessel volume ( r =0.55, P &lt;0.0001) and between the QCA cumulative coronary stenosis score and percent atheroma volume on IVUS ( r =0.32, P &lt;0.0001) at baseline for matched segments. A similar pattern of correlations was observed for global (all segments) QCA-derived and single-vessel IVUS-derived data. There were statistically significant but weak correlations between the changes over time in lumen dimensions on QCA and IVUS ( P =0.005) and between the change in cumulative coronary stenosis score on QCA and percent atheroma volume on IVUS ( r =0.14, P =0.01). Nevertheless, patients with and without angiographic progression had changes in plaque volume on IVUS of 9.13 and 0.20 mm 3 , respectively ( P =0.028). Conclusions— QCA- and IVUS-derived measures of lumen dimensions are correlated at single time points and for changes over time. Although the change in percent atheroma volume is only weakly correlated with QCA changes as continuous variables, disease progression on QCA is associated with significant increases in plaque volume on IVUS compared with no angiographic progression.
Meta-analysis: Diagnostic Accuracy of Anti–Cyclic Citrullinated Peptide Antibody and Rheumatoid Factor for Rheumatoid Arthritis
Authors: Kunihiro Nishimura, Daisuke Sugiyama, Yoshinori Kogata, Goh Tsuji, Takashi Nakazawa, Seiji Kawano, Katsuyasu Saigo, Akio Morinobu, Masahiro Koshiba, Karen M. Kuntz, Isao Kamae, Shunichi Kumagai
Journal: Annals of Internal Medicine (2007)

Background: Rheumatoid factor (RF) and autoantibodies against cyclic citrullinated peptide (CCP) are markers that might help physicians diagnose rheumatoid arthritis. Purpose: To determine whether anti-CCP antibody more accurately identifies patients with rheumatoid arthritis and better predicts radiographic progression than does RF. Data Sources: MEDLINE through September 2006 and reference lists of retrieved studies and review articles. Study Selection: Studies in any language that enrolled at least 10 participants and that examined the role of anti-CCP antibody and RF in the diagnosis or prognosis of known or suspected rheumatoid arthritis. Data Extraction: Two authors independently evaluated studies for inclusion, rated methodological quality, and abstracted relevant data. Data Synthesis: The DerSimonian–Laird random-effects method was used to summarize sensitivities, specificities, and positive and negative likelihood ratios from 37 studies of anti-CCP antibody and 50 studies of RF. The pooled sensitivity, specificity, and positive and negative likelihood ratios for anti-CCP antibody were 67% (95% CI, 62% to 72%), 95% (CI, 94% to 97%), 12.46 (CI, 9.72 to 15.98), and 0.36 (CI, 0.31 to 0.42), respectively. For IgM RF, the values were 69% (CI, 65% to 73%), 85% (CI, 82% to 88%), 4.86 (CI, 3.95 to 5.97), and 0.38 (CI, 0.33 to 0.44). Likelihood ratios among IgM RF, IgG RF, and IgA RF seemed to be similar. Results from studies of patients with early rheumatoid arthritis were similar to those from all studies. Three of 4 studies found that risk for radiographic progression was greater with anti-CCP antibody positivity than with IgM RF positivity. Limitations: Many studies had methodological limitations. Studies of RF were heterogeneous and had wide ranges of sensitivity and specificity. Conclusions: Anti-CCP antibodies are more specific than RF for diagnosing rheumatoid arthritis and may better predict erosivedisease.
AKAP150 Is Required for Stuttering Persistent Ca <sup>2+</sup> Sparklets and Angiotensin II–Induced Hypertension
Authors: Manuel F. Navedo, Madeline Nieves-Cintrón, Gregory C. Amberg, Can Yuan, V. Scott Votaw, W. Jonathan Lederer, G. Stanley McKnight, Luis F. Santana
Journal: Circulation Research (2008)

Hypertension is a perplexing multiorgan disease involving renal primary pathology and enhanced angiotensin II vascular reactivity. Here, we report that a novel form of a local Ca2+ signaling in arterial smooth muscle is linked to the development of angiotensin II-induced hypertension. Long openings and reopenings of L-type Ca2+ channels in arterial myocytes produce stuttering persistent Ca2+ sparklets that increase Ca2+ influx and vascular tone. These stuttering persistent Ca2+ sparklets arise from the molecular interactions between the L-type Ca2+ channel and protein kinase Calpha at only a few subsarcolemmal regions in resistance arteries. We have identified AKAP150 as the key protein, which targets protein kinase Calpha to the L-type Ca2+ channels and thereby enables its regulatory function. Accordingly, AKAP150 knockout mice (AKAP150-/-) were found to lack persistent Ca2+ sparklets and have lower arterial wall intracellular calcium ([Ca2+]i) and decreased myogenic tone. Furthermore, AKAP150-/- mice were hypotensive and did not develop angiotensin II-induced hypertension. We conclude that local control of L-type Ca2+ channel function is regulated by AKAP150-targeted protein kinase C signaling, which controls stuttering persistent Ca2+ influx, vascular tone, and blood pressure under physiological conditions and underlies angiotensin II-dependent hypertension.
Topical nasal anaesthesia for fibreoptic bronchoscopy: patients' preference for lignocaine gel.
Authors: A R Webb, M A Woodhead, H R Dalton, J A Grigg, F J Millard
Journal: Thorax (1989)

Two techniques for anaesthetising the nose before fibreoptic bronchoscopy have been compared. Fourteen of 16 patients given lignocaine spray found it unpleasant, compared with three of 20 patients given lignocaine gel. The two forms of local anaesthetic were found to be equally effective. Lignocaine gel is therefore recommended for topical nasal anaesthesia before fibreoptic bronchoscopy.
Plasma-seq: a novel strategy for metastatic prostate cancer analysis
Authors: Caitlin Farris, Jeffrey M Trimarchi
Journal: Genome Medicine (2013)

Personalized genomics will only be useful for monitoring the prognosis of patients with cancer when it becomes much more cost-effective and quicker to apply. A recent study brings this closer to reality with the development of plasma-seq, a rapid, low-cost method that sequences the circulating DNA present in the peripheral blood of patients with cancer. The power of this technique is demonstrated with the examination of tumor genomes from patients with prostate cancer. See related research article: http://genomemedicine.com/content/5/4/30
Comparison of Baseline–Nitrate Technetium-99m Sestamibi With Rest–Redistribution Thallium-201 Tomography in Detecting Viable Hibernating Myocardium and Predicting Postrevascularization Recovery
Authors: Roberto Sciagrà, Gianni Bisi, Giovanni M Santoro, Francesca Zerauschek, Stelvio Sestini, Paola Pedenovi, Ruggiero Pappagallo, Pier Filippo Fazzini
Journal: Journal of the American College of Cardiology (1997)
Early Detection and Prognosis of Ovarian Cancer Using Serum YKL-40
Authors: Jakob Dupont, Meena K. Tanwar, Howard T. Thaler, Martin Fleisher, Noah Kauff, Martee L. Hensley, Paul Sabbatini, Sibyl Anderson, Carol Aghajanian, Eric C. Holland, David R. Spriggs
Journal: Journal of Clinical Oncology (2004)

Purpose YKL-40 is a secreted glycoprotein (chitinase family). We compared YKL-40 with two ovarian cancer serum markers, CA125 and CA15-3, for the detection of early-stage ovarian cancer. Materials and Methods Serum YKL-40 levels were assayed by enzyme-linked immunosorbent assay for 46 healthy subjects, 61 high-risk individuals, 33 patients with benign gynecologic processes, and 50 preoperative patients subsequently diagnosed with predominantly early-stage ovarian cancer. Serum CA125 and CA15-3 values were obtained. Results Median YKL-40 level was 28 ng/mL (range, 15 to 166 ng/mL) for healthy subjects, 36 ng/mL (range, 9 to 69 ng/mL) for high-risk individuals without prior cancer, 44.5 ng/mL (range, 5 to 133 ng/mL) for high-risk patients with prior breast cancer, and 38 ng/mL (range, 5 to 67 ng/mL) for individuals with benign gynecologic processes (P = NS). Median preoperative YKL-40 level for ovarian cancer patients was 94 ng/mL (range, 17 to 517 ng/mL; P &lt; .0001 compared with normal and high-risk). YKL-40 was elevated (≥ 62 ng/mL) in 36 (72%) of 50 patients compared with 23 (46%) of 50 and 13 (26%) of 50 patients for CA125 and CA15-3 (P &lt; .008). Twenty (65%) of 31 early-stage patients had elevated serum YKL-40 levels compared with 11 (35%) of 31 and four (13%) of 31 patients for CA125 and CA15-3 (P = .039). YKL-40 levels increased with stage (P &lt; .005), regardless of grade, histology, or patient age. Patients with early-stage tumors with YKL-40 values more than 80 ng/mL had a worse prognosis (71% recurrence v no recurrence [P = .034]). Conclusion YKL-40 may represent a novel marker for the detection of early-stage ovarian cancer. YKL-40 levels in early-stage patients may also predict disease recurrence and survival. The utility of YKL-40 in detection of early-stage ovarian cancer deserves further investigation.
Force-velocity relation and myosin light chain phosphorylation in bovine coronary arterial smooth muscle.
Authors: W C Miller-Hance, K E Kamm
Journal: Circulation Research (1991)

We have investigated in bovine left ventricular coronary arteries the relation between the biochemical regulatory event of myosin light chain phosphorylation and the mechanical events of isometric stress and isotonic shortening, under conditions of stimulation by depolarization (65 mM KCl) or receptor occupancy (2 microM 5-hydroxytryptamine [5-HT]). At rest, levels of light chain phosphorylation were 0.07 +/- 0.01 mol phosphate/mol light chain. Maximal values were significantly different for KCl (0.42 +/- 0.02 mol phosphate/mol light chain at 1 minute) and 5-HT stimulation (0.58 +/- 0.01 mol phosphate/mol light chain at 30 seconds). Increases in light chain phosphorylation preceded isometric stress development, and values remained elevated at approximately 0.35 mol phosphate/mol light chain for up to 2 hours with both KCl and 5-HT. The sites of phosphorylation were identical for KCl and 5-HT at 2 hours. Maximal stresses for each stimulus were also maintained for 2 hours. Values of maximum velocity of shortening (Vo in muscle lengths [ML]/sec), obtained from the force-velocity relation, did not change significantly between 1 minute and 2 hours with KCl (0.070 +/- 0.008 ML/sec at 1 minute and 0.056 +/- 0.007 ML/sec at 2 hours, p greater than 0.2). However, during 5-HT stimulation, Vo declined significantly (0.053 +/- 0.006 ML/sec at 1 minute and 0.032 +/- 0.003 ML/sec at 2 hours, p less than 0.025). The relation between Vo and light chain phosphorylation was different for KCl and 5-HT, indicating that factors in addition to myosin light chain phosphorylation may modulate smooth muscle shortening velocity.
Cardiac surgeons call for more doctors to use outcome data to improve care
Authors: A. O'Dowd
Journal: BMJ (2011)

Much of the NHS is failing to give patients crucial information that would help them make truly informed decisions about their care and where to have it, concludes a report by the cardiac surgeons’ representative body.

Cardiac surgeons have hit out at the rest of the NHS, saying that, outside cardiac surgery, doctors are not providing reliable, independent, and accessible data on outcomes. The government has now announced that an additional £1.2m (€1.4m; $1.9m) will be allocated in the next year for clinical audits in the NHS in England.

The new report by the Society of Cardiothoracic Surgery in Great Britain and Ireland criticises the lack of information given by many doctors. The report, launched today at the …
Clinical outcomes of health-care-associated infections and antimicrobial resistance in patients admitted to European intensive-care units: a cohort study
Authors: Marie-Laurence Lambert, Carl Suetens, Anne Savey, Mercedes Palomar, Michael Hiesmayr, Ingrid Morales, Antonella Agodi, Uwe Frank, Karl Mertens, Martin Schumacher, Martin Wolkewitz
Journal: The Lancet Infectious Diseases (2010)
Measurement of airway hyperresponsiveness: new considerations
Authors: J. Lotvall, M. Inman, P. O'Byrne
Journal: Thorax (1998)

Since its initial descriptions in 1946,1 the measurement of airway responsiveness with inhaled bronchoconstrictor stimuli such as methacholine or histamine has become routine practice in the diagnosis and follow up of asthmatic patients. Practically, this involves the patient inhaling increasing doses or concentrations of a stimulus until a given level of bronchoconstriction is achieved, typically a 20% fall in forced expired volume in one second (FEV1). Airway responsiveness is then expressed as the provocative dose or concentration of the stimulus required to achieve this degree of bronchoconstriction (PD20 and PC20, respectively).

The term “airway responsiveness” is preferred when discussing PD20 and PC20 measurements as this is a non-specific term that encompasses the underlying mechanisms that may be responsible for differences in these measurements either between individuals or within an individual over time2. This is best illustrated in fig 1 where it can be seen that a decrease in PC20 may be due to a steeper dose-response curve (hyperreactivity) or to a shift in the curve to the left (hypersensitivity), or both. Thus, when an individual displays a decreased PC20 it is usually not known whether this is due to hyperreactivity or hypersensitivity although it is certainly one, the other, or both—all of which are covered by the term airway “hyperresponsiveness”.



Figure 1 
Changes in FEV1 induced by increasing doses of a bronchoconstrictor stimulus such as histamine or methacholine. Bronchial hyperresponsiveness, defined as the dose causing a 20% fall in FEV1, can be induced by airway hypersensitivity (shift to the left of the dose-response curve) or airway hyperreactivity (steeper slope of the dose-response curve). This figure illustrates how either of these two different mechanisms may result in the same degree of hyperresponsiveness (as measured by a shift in PC …
Randomized Phase II Trial of the Efficacy and Safety of Trastuzumab Combined With Docetaxel in Patients With Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer Administered As First-Line Treatment: The M77001 Study Group
Authors: Michel Marty, Francesco Cognetti, Dominique Maraninchi, Ray Snyder, Louis Mauriac, Michèle Tubiana-Hulin, Stephen Chan, David Grimes, Antonio Antón, Ana Lluch, John Kennedy, Kenneth O’Byrne, PierFranco Conte, Michael Green, Carol Ward, Karen Mayne, Jean-Marc Extra
Journal: Journal of Clinical Oncology (2005)

Purpose This randomized, multicenter trial compared first-line trastuzumab plus docetaxel versus docetaxel alone in patients with human epidermal growth factor receptor 2 (HER2) –positive metastatic breast cancer (MBC). Patients and Methods Patients were randomly assigned to six cycles of docetaxel 100 mg/m 2 every 3 weeks, with or without trastuzumab 4 mg/kg loading dose followed by 2 mg/kg weekly until disease progression. Results A total of 186 patients received at least one dose of the study drug. Trastuzumab plus docetaxel was significantly superior to docetaxel alone in terms of overall response rate (61% v 34%; P = .0002), overall survival (median, 31.2 v 22.7 months; P = .0325), time to disease progression (median, 11.7 v 6.1 months; P = .0001), time to treatment failure (median, 9.8 v 5.3 months; P = .0001), and duration of response (median, 11.7 v 5.7 months; P = .009). There was little difference in the number and severity of adverse events between the arms. Grade 3 to 4 neutropenia was seen more commonly with the combination (32%) than with docetaxel alone (22%), and there was a slightly higher incidence of febrile neutropenia in the combination arm (23% v 17%). One patient in the combination arm experienced symptomatic heart failure (1%). Another patient experienced symptomatic heart failure 5 months after discontinuation of trastuzumab because of disease progression, while being treated with an investigational anthracycline for 4 months. Conclusion Trastuzumab combined with docetaxel is superior to docetaxel alone as first-line treatment of patients with HER2-positive MBC in terms of overall survival, response rate, response duration, time to progression, and time to treatment failure, with little additional toxicity.
MEMORY AS A BIOLOGICAL FUNCTION
Authors: ROLAND P. MACKAY
Journal: American Journal of Psychiatry (1953)

From these reflections it appears that memory is a basic attribute of all living things, by which patterns of sensitivity and response, both inborn and acquired, are retained and progressively modified under the impact of experience. Memory is thus indispensable in all behavior, making it at once consistent and modifiable. A consideration of some of the classical psychologic features of memory indicates the extent to which it involves multimodal processes and hence extremely widespread cerebral areas. In the higher animals and in man therefore, memory can have no precise localization and thus cannot be said to "reside" in the temporal lobe or in any other restricted area. In the simplest organisms memory seems to be dependent upon modifiable molecular structure; its mechanism in a nervous system is a most elusive function of neuronal networks by which topographic and sequential patterns of stimuli sensitize the network to subsequent stimuli in the same patterns, probably through the device of summation in reverberating circuits rather than by the facilitation of anatomical pathways. Sketchy and hypothetical though our present knowledge is, this dynamic approach to the physiology of memory promises much for our understanding of the behavior of living things.
Clinical Performance and Specialty Choice of COTRANS Students
Authors: Barry Stimmel
Journal: JAMA (1979)

The clinical performance and specialty choice of 33 Coordinated Transfer Application System (COTRANS) students accepted with advanced standing into the third year of an American medical school were compared with the performance and choice of students from other American medical schools. The undergraduate grade point average of the COTRANS group was considerably lower than that of the other students. The science Medical College Admission Test scores in science were comparable, and the performance on part I of the National Board of Medical Examiners was considerably higher. Clinical performance, choice of specialty, and affiliation of graduate program of the COTRANS students did not differ from those of students entering the curriculum in year 1. Carefully selected students completing the first two years of basic science in a foreign medical school can successfully compete with students already enrolled in the American medical curriculum. (<i>JAMA</i>241:139-142, 1979)