tbuckley/cabot-search huggingface dataset:
Patient pain drawing in diagnosing the cause of exercise-induced leg pain
Authors: K Rennerfelt, Q Zhang, L Hamilton, J Styf
Journal: British Journal of Sports Medicine (2011)

Introduction Classifying symptoms by patient pain drawing (PPD) may be helpful in diagnosing chronic anterior compartment syndrome (CACS). We have investigated the sensitivity and interobserver reliability of the PPD to diagnose CACS among patients with exercise-induced leg pain (EILP). Methods This study included 88 consecutive patients (48 men, 40 women; mean age 33, range 13–66, years). Two observers independently diagnosed the causes of leg pain based solely on PPD. The causes of leg pain in patients were diagnosed into seven categories (CACS, chronic lateral compartment syndrome, chronic posterior compartment syndrome, medial tibial syndrome, peroneal tunnel syndrome, muscle rupture and miscellaneous). The true diagnosis was based on a complete clinical examination including laboratory measurements of intramuscular pressure and intramuscular oxygenation by near-infrared spectroscopy during and after an exercise test that elicited the symptoms. Results The sensitivity of PPD to diagnose CACS was 69%. The positive predictive value was 53%. The interobserver reliability based solely on PPD in diagnosis of CACS was 92% (κ=0.81). Based on PPD, the causes of EILP were correctly diagnosed into the seven categories in 69% of all cases. The interobserver reliability in diagnosis of EILP reached 88%. Multiple pain locations on PPD were observed in 4% of patients with CACS and 24% of patients without CACS. No patient had chronic compartment syndrome in the lateral or posterior compartments. Conclusions This study indicates that PPD is a reliable tool to make accurate predictions in diagnosing CACS and other causes of EILP. Patients with CACS reported significantly less co-morbidity compared to patients with other causes of EILP. PPD should be combined with patient's history, clinical findings during an exercise test that elicits the symptoms and signs, as well as with the results from laboratory tests.
Imatinib Mesylate Inhibits Leydig Cell Tumor Growth: Evidence for <i>In vitro</i> and <i>In vivo</i> Activity
Authors: Sabrina Basciani, Marina Brama, Stefania Mariani, Gabriele De Luca, Mario Arizzi, Loredana Vesci, Claudio Pisano, Susanna Dolci, Giovanni Spera, Lucio Gnessi
Journal: Cancer Research (2005)

Abstract Leydig cell tumors are usually benign tumors of the male gonad. However, if the tumor is malignant, no effective treatments are currently available. Leydig cell tumors express platelet-derived growth factor (PDGF), kit ligand and their respective receptors, PDGFR and c-kit. We therefore evaluated the effects of imatinib mesylate (imatinib), a selective inhibitor of the c-kit and PDGFR tyrosine kinases, on the growth of rodent Leydig tumor cell lines in vivo and in vitro, and examined, in human Leydig cell tumor samples, the expression of activated PDGFR and c-kit and the mutations in exons of the c-kit gene commonly associated with solid tumors. Imatinib caused concentration-dependent decreases in the viability of Leydig tumor cell lines, which coincided with apoptosis and inhibition of proliferation and ligand-stimulated phosphorylation of c-kit and PDGFRs. Mice bearing s.c. allografts of a Leydig tumor cell line treated with imatinib p.o., had an almost complete inhibition of tumor growth, less tumor cell proliferation, increased apoptosis, and a lesser amount of tumor-associated mean vessel density compared with controls. No drug-resistant tumors appeared during imatinib treatment but tumors regrew after drug withdrawal. Human Leydig cell tumors showed an intense expression of the phosphorylated form of c-kit and a less intense expression of phosphorylated PDGFRs. No activating mutations in common regions of mutation of the c-kit gene were found. Our studies suggest that Leydig cell tumors might be a potential target for imatinib therapy.
Gene transfer and cell transplant: an experimental approach to repair a 'broken heart'
Authors: Jonathan Leor, Howard Prentice, Vittorio Sartorelli, Manuel J Quinones, Michael Patterson, Laurence K Kedes, Robert A Kloner
Journal: Cardiovascular Research (1997)

Time for primary review 22 days.

Despite significant progress in prevention and therapy of ischemic heart disease, treating patients with heart failure after myocardial infarction remains a major therapeutic challenge. Adult cardiomyocytes cannot regenerate after injury. Therefore, cardiomyocyte loss due to myocardial infarction is irreversible. Currently, congestive heart failure is the only major cardiovascular disorder that is increasing in incidence and mortality [1]. Thus, there is still a need to develop alternative therapeutic strategies to prevent, arrest or reverse congestive heart failure after myocardial infarction.

Recent insights into the pathogenesis of myocardial disease and advances in molecular biology have opened up a new era of molecular and cellular therapies that target genes, molecules and peptides. Gene transfer as a therapeutic approach for the treatment of myocardial infarction and congestive heart failure has been suggested as a new treatment strategy for these serious disorders [2, 3]. The introduction, into injured myocardium, of recombinant transgenes that encode growth factors, could stimulate new vessel formation with increased collateral blood flow, accelerate healing and enhance myocardial performance. Today it is even possible to consider genetic manipulation leading to regeneration of myocytes within the infarcted myocardium.

An alternative experimental strategy to increase viability and augment ventricular function after myocardial infarction is cell transplantation [4]. Engrafted fetal cells might increase the number of functional myocytes in the infarcted myocardium, could serve as a potential source of growth factors and could be programmed for myocyte-based gene transfer.

The purpose of our review is to summarize recent advances in the attempts to develop molecular and cellular strategies for repairing a ‘broken heart’. The biological rationale for these new therapies and the potential limitations of gene therapy and cell transplant in treating myocardial infarction are discussed.

Left ventricular remodeling following myocardial infarction refers to the process … 

* Corresponding author. The Heart Institute, Good Samaritan Hospital, 1225 Wilshire Blvd., Los Angeles, CA 90017, USA. Tel.: +1 (213) 977 4050; fax: +1 (213) 977 4107.
Five-Year Follow-up of Patients Receiving Imatinib for Chronic Myeloid Leukemia
Authors: Brian J. Druker, François Guilhot, Stephen G. O'Brien, Insa Gathmann, Hagop Kantarjian, Norbert Gattermann, Michael W.N. Deininger, Richard T. Silver, John M. Goldman, Richard M. Stone, Francisco Cervantes, Andreas Hochhaus, Bayard L. Powell, Janice L. Gabrilove, Philippe Rousselot, Josy Reiffers, Jan J. Cornelissen, Timothy Hughes, Hermine Agis, Thomas Fischer, Gregor Verhoef, John Shepherd, Giuseppe Saglio, Alois Gratwohl, Johan L. Nielsen, Jerald P. Radich, Bengt Simonsson, Kerry Taylor, Michele Baccarani, Charlene So, Laurie Letvak, Richard A. Larson
Journal: New England Journal of Medicine (2006)

The cause of chronic myeloid leukemia (CML) is a constitutively active BCR-ABL tyrosine kinase. Imatinib inhibits this kinase, and in a short-term study was superior to interferon alfa plus cytarabine for newly diagnosed CML in the chronic phase. For 5 years, we followed patients with CML who received imatinib as initial therapy.We randomly assigned 553 patients to receive imatinib and 553 to receive interferon alfa plus cytarabine and then evaluated them for overall and event-free survival; progression to accelerated-phase CML or blast crisis; hematologic, cytogenetic, and molecular responses; and adverse events.The median follow-up was 60 months. Kaplan-Meier estimates of cumulative best rates of complete cytogenetic response among patients receiving imatinib were 69% by 12 months and 87% by 60 months. An estimated 7% of patients progressed to accelerated-phase CML or blast crisis, and the estimated overall survival of patients who received imatinib as initial therapy was 89% at 60 months. Patients who had a complete cytogenetic response or in whom levels of BCR-ABL transcripts had fallen by at least 3 log had a significantly lower risk of disease progression than did patients without a complete cytogenetic response (P<0.001). Grade 3 or 4 adverse events diminished over time, and there was no clinically significant change in the profile of adverse events.After 5 years of follow-up, continuous treatment of chronic-phase CML with imatinib as initial therapy was found to induce durable responses in a high proportion of patients. (ClinicalTrials.gov number, NCT00006343 [ClinicalTrials.gov].)
MAJOR PSYCHIATRIC CONSIDERATIONS IN A SERVICE COMMAND
Authors: FRANKLIN G. EBAUGH
Journal: American Journal of Psychiatry (1943)

In this presentation of psychiatric problems of a Service Command the deficiencies have been stressed and corrective measures have been outlined. We feel that military psychiatry consists of close integration of the levels of selection, prevention, therapy, education and administration. If we are to have more effective neuropsychiatry in our Service Command, the following requirements should be met: (a) The assignment of skilled neuropsychiatric examiners to each induction station who will have at hand social histories. (b) The assignment of experienced neuropsychiatric officers to each reception center and replacement training center whose efforts will be directed predominantly toward additional psychiatric screening, treatment of mild disorders, and prevention of potential psychiatric casualties. (c) The institution of methods to improve the neuropsychiatric work in fixed hospital units by: 1. A decrease in the excessive clinical load; 2. An increase in the numbers and effectiveness of the neuropsychiatric personnel and allied aides. (d) The continued development of sound educational and administrative procedures.
The effects of a university fitness programme on health-related variables in previously sedentary males.
Authors: S Grant, T Aitchison, A R Pettigrew, J M Orrell
Journal: British Journal of Sports Medicine (1992)

This study reports on the effects of a 10-week university fitness programme on health-related fitness variables. Twenty-one male exercisers, aged 37.0(10.3) years (mean(s.d.); range 21-58), and 22 male controls, aged 38.6(7.9) years (mean(s.d.); range 17-54), volunteered to take part. Two sample t-tests and 95% confidence intervals were used to determine if the exercise group demonstrated a greater average improvement than the control group and the average improvement in both groups separately. The exercise group showed a greater average improvement over the controls from Test 1 (before fitness programme) to Test 2 (after) in the following: steady-state heart rate (beats min-1) 95% confidence intervals (-7.8, -16.2); predicted VO2max (ml kg-1 min-1): 95% confidence intervals (3.2, 6.6); sit-ups (repetitions): 95% confidence intervals (3.1, 7.0); flexibility (cm): 95% confidence intervals (3.3, 6.9). There was no significant difference between the exercise group and control group in body weight, percentage body fat, blood pressure, total plasma cholesterol, high-density lipoprotein and triglycerides. The exercise programme improved aerobic fitness, local muscular endurance and flexibility. However, the increase in aerobic fitness did not coincide with beneficial changes in the coronary risk profile.
Dendritic cell expression of the transcription factor T-bet regulates mast cell progenitor homing to mucosal tissue
Authors: Pilar Alcaide, Tatiana G. Jones, Graham M. Lord, Laurie H. Glimcher, Jenny Hallgren, Yojiro Arinobu, Koichi Akashi, Alison M. Paterson, Michael A. Gurish, Francis W. Luscinskas
Journal: The Journal of Experimental Medicine (2007)

The transcription factor T-bet was identified in CD4(+) T cells, and it controls interferon gamma production and T helper type 1 cell differentiation. T-bet is expressed in certain other leukocytes, and we recently showed (Lord, G.M., R.M. Rao, H. Choe, B.M. Sullivan, A.H. Lichtman, F.W. Luscinskas, and L.H. Glimcher. 2005. Blood. 106:3432-3439) that it regulates T cell trafficking. We examined whether T-bet influences homing of mast cell progenitors (MCp) to peripheral tissues. Surprisingly, we found that MCp homing to the lung or small intestine in T-bet(-/-) mice is reduced. This is reproduced in adhesion studies using bone marrow-derived MCs (BMMCs) from T-bet(-/-) mice, which showed diminished adhesion to mucosal addresin cellular adhesion molecule-1 (MAdCAM-1) and vascular cell adhesion molecule-1 (VCAM-1), endothelial ligands required for MCp intestinal homing. MCp, their precursors, and BMMCs do not express T-bet, suggesting that T-bet plays an indirect role in homing. However, adoptive transfer experiments revealed that T-bet expression by BM cells is required for MCp homing to the intestine. Furthermore, transfer of WT BM-derived dendritic cells (DCs) to T-bet(-/-) mice restores normal MCp intestinal homing in vivo and MCp adhesion to MAdCAM-1 and VCAM-1 in vitro. Nonetheless, T-bet(-/-) mice respond vigorously to intestinal infection with Trichinella spiralis, eliminating a role for T-bet in MC recruitment to sites of infection and their activation and function. Therefore, remarkably, T-bet expression by DCs indirectly controls MCp homing to mucosal tissues.
Mediastinal malignancy: ultrasound guided biopsy through the supraclavicular approach.
Authors: P C Yang, D B Chang, Y C Lee, C J Yu, S H Kuo, K T Luh
Journal: Thorax (1992)

Malignancies located in the upper middle mediastinum usually do not have a sufficiently large acoustic window to permit a conventional ultrasound guided parasternal biopsy. This study was concerned with an alternative approach whereby ultrasound is applied through the supraclavicular paratracheal window to allow percutaneous biopsy of middle mediastinal malignancies.Fifteen patients who had upper mediastinal malignancies not in contact with the chest wall underwent real time and Doppler ultrasonographic studies by the supraclavicular approach. None of these tumours could be reached by conventional ultrasound guided parasternal biopsy. The ultrasound was scanned downwards through the supraclavicular fossa, along the acoustic window of the paratracheal soft tissue space. Percutaneous aspiration biopsy was performed with a 22 gauge needle under ultrasound guidance. If fine needle aspiration could not obtain an adequate tissue smear an 18 gauge Trucut biopsy was performed to obtain a histological diagnosis.Twelve of 15 mediastinal malignancies were detected by ultrasound through the supraclavicular approach. These 12 patients underwent percutaneous needle aspiration biopsy under ultrasound guidance. Four of the patients also had a Trucut biopsy because the needle aspirates from the tumours were inadequate. The needle had to pass through the jugular veins in four patients who received fine needle aspiration but in none of the patients who required a Trucut biopsy. Definite histological diagnoses were obtained in all 12 of these patients. Ten of the tumours were malignant and two benign. None of the patients developed any complication.Ultrasound and ultrasound guided biopsy through the supraclavicular paratracheal window provides a new approach for malignancy located in the upper middle mediastinum, which cannot be reached by conventional ultrasound guided parasternal biopsy. The diagnostic yield of this technique is high and the procedure is relatively safe.
Competitive time- and density-dependent adhesion of staphylococci and osteoblasts on crosslinked poly(ethylene glycol)-based polymer coatings in co-culture flow chambers
Authors: Isabel C. Saldarriaga Fernández, Henk J. Busscher, Steve W. Metzger, David W. Grainger, Henny C. van der Mei
Journal: Biomaterials (2010)
Intermittent Androgen Suppression for Rising PSA Level after Radiotherapy
Authors: Juanita M. Crook, Christopher J. O'Callaghan, Graeme Duncan, David P. Dearnaley, Celestia S. Higano, Eric M. Horwitz, Eliot Frymire, Shawn Malone, Joseph Chin, Abdenour Nabid, Padraig Warde, Thomas Corbett, Steve Angyalfi, S. Larry Goldenberg, Mary K. Gospodarowicz, Fred Saad, John P. Logue, Emma Hall, Paul F. Schellhammer, Keyue Ding, Laurence Klotz
Journal: New England Journal of Medicine (2012)

Intermittent androgen deprivation for prostate-specific antigen (PSA) elevation after radiotherapy may improve quality of life and delay hormone resistance. We assessed overall survival with intermittent versus continuous androgen deprivation in a noninferiority randomized trial.
Local Immune Responses Correlate with Presentation and Outcome in Tuberculosis
Authors: RANY CONDOS, WILLIAM N. ROM, YUK MING LIU, NEIL W. SCHLUGER
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Local cellular immune responses may affect presentation and outcome in tuberculosis (TB). To investigate this hypothesis, we performed bronchoalveolar lavage (BAL) on 30 patients with untreated pulmonary tuberculosis and assessed the type of cellular inflammatory response and cytokine production. We then correlated BAL findings and cytokine production with clinical findings. We also performed BAL on a subset of patients to examine changes in cytokine production by BAL cells over time. We found that at presentation patients with less clinically and radiographically advanced TB (smear-negative, noncavitary disease) had a local immune response characterized by a predominance of lymphocytes. Furthermore, BAL cells from these patients secreted interferon (IFN γ ), and not Interleukin-4, suggesting a Th 1-type lymphocytic response. In patients with smear-positive and/or cavitary disease, macrophages or polymorphonuclear leukocytes were the predominant BAL cell type, but with treatment and clinical improvement these patients went on to recruit IFN γ producing cells to the lung. We conclude that the type of cellular immune response that occurs locally in the lung may affect presentation and outcome in pulmonary TB, and an understanding of the development of this response may lead to insights into pathogenesis and novel therapies for TB.
Integrating exemplars in category learning: Better late than never, but better early than late
Authors: J. Eric Ivancich, David A. Schwartz, Stephen Kaplan
Journal: Behavioral and Brain Sciences (2000)

Page's target article makes a good case for the strength of localist models. This can be characterized as an issue of where new information is integrated with respect to existing knowledge structures. We extend the analysis by discussing the dimension of when this integration takes place, the implications, and how they guide us in the creation of cognitive models.
Neurally mediated depressor hemodynamic response induced by intracoronary catheter balloon inflation in pigs
Authors: J Cinca
Journal: Cardiovascular Research (2000)

Objectives: To assess whether intracoronary catheter balloon inflation triggers a neurally mediated hemodynamic response that interacts with the ischemia-induced myocardial dysfunction. Methods: Forty-eight chloralose anesthetized pigs underwent a 60 s intraluminal catheter balloon inflation of the proximal left anterior descending (LAD) coronary artery before and after one of these treatments: disruption of LAD pericoronary nerves with phenol (n=6), bilateral stellectomy (n=8), bilateral cervical vagotomy (n=6), atropine (n=5), and ganglionic blockade with hexamethonium (n=10). In 13 other pigs, we assessed the reproducibility of two balloon inflations spaced 15 min (n=6) or 60 min (n=7). The ECG, left ventricular (LV) pressure, and LV dP/dt were recorded during each intervention. Right ventricular (RV) pressure, RV dP/dt, and aortic blood flow were also measured in a subset of pigs. Results: Balloon inflation induced an early (10 s) and reproducible (ANOVA, P<0.001) drop in systolic pressure and peak dP/dt; a decrease in aortic blood flow; a rise in end-diastolic pressure; and elevation of the ST segment. Pericoronary denervation, stellectomy and ganglionic blockade attenuated (P<0.001) the drop in LV parameters during coronary inflation, but atropine and vagotomy did not. Conclusions: A depressor hemodynamic response subserved by pericoronary nerves worsens the LV dysfunction induced by brief coronary catheter balloon inflation in anesthetized pigs. Cholinergic fibers do not appear to play a major role.
Clinical significance of autoantibodies in a large cohort of patients with chronic graft‐versus‐host disease defined by NIH criteria
Authors: Zoya Kuzmina, Verena Gounden, Lauren Curtis, Daniele Avila, Tiffani Taylor RNP, Judy Baruffaldi, Edward W. Cowen, Haley B. Naik, Sarfaraz A. Hasni, Jacqueline W. Mays, Sandra Mitchell, Kristin Baird, Seth M. Steinberg, Steven Z. Pavletic
Journal: American Journal of Hematology (2014)

There is an unmet need for identifying new clinical biomarkers in chronic Graft-versus-Host-disease (cGVHD) suitable for diagnosis and disease monitoring. Circulating autoantibodies represent an ongoing immune response and suggest a pathogenic role for B cells in cGVHD. Autoantibodies could be useful markers of cGVHD disease activity, severity, or organ specificity; however, their clinical utility is not established. The focus of this study was to determine the incidence and associations of a broad array of clinical autoantibodies with cGVHD manifestations in a large patient cohort characterized by NIH criteria. A panel of 21 circulating antibodies commonly used in clinical medicine was tested in 280 cGVHD patients (70% severe) enrolled in a cross-sectional prospective natural history study. Median cGVHD duration was two years. Patients with circulating autoantibodies (62%) had significantly higher levels of IgM (P < 0.0001), IgG (P < 0.0001), and IgA (P = 0.001), elevated uric acid (P = 0.008) and total protein (P = 0.0004), and higher numbers of CD3+ (P = 0.002), CD4+ (P = 0.001), CD8+ (P = 0.023) T cells, and CD19+ B cells (P < 0.0001). Multiple antibodies were detected in 35% of patients. Prior rituximab therapy (n = 66) was associated with reduced presence of autoantibodies (48 vs. 66% P = 0.01). Only oral cGVHD was significantly associated with presence of autoantibodies in this study (P = 0.028). No significant associations were found between cGVHD activity and severity, and presence of autoantibodies. Circulating autoantibodies are common in patients with advanced cGVHD. Their presence is associated with better quantitative immunologic reconstitution but does not have utility as a clinical biomarker of cGVHD.
Mechanisms of Action of Nonglucose Insulin Secretagogues
Authors: Y Liang, F M Matschinsky
Journal: Annual Review of Nutrition (1994)

Insulin release induced by nonglucose secretagogues is initiated from beta-cell by a wide variety of stimuli through specific receptors or binding sites. Activation of receptors in turn generates or enhances the cytosol levels of cAMP, cADPR, IP3, DAG, and AA. These second messengers then activate protein kinases, change the ion currents cross the cell membrane, and mobilize intracellular Ca2+, thereby increasing phosphorylated proteins in the cytosol and augmenting [Ca2+]i. These events trigger exocytotic discharge of insulin. The crucial steps in receptor-mediated stimulation-secretion coupling and their relationship to glucose-stimulated insulin release is summarized in Figure 1. At the present stage of research, the general processes of secretagogue binding to receptors, of generating second messengers, of activating several types of protein kinase, and of altering the membrane potential as well as cytosol calcium levels has been intensively studied and qualitatively clarified. However, we know little about the exact nature of substrates of different protein kinases and their function in the insulin secretion process. With the help of molecular biology and protein chemistry, we expect that this gap will be filled in the near future.