tbuckley/cabot-search huggingface dataset:
Phase I/II Trial Assessing Bortezomib and Melphalan Combination Therapy for the Treatment of Patients With Relapsed or Refractory Multiple Myeloma
Authors: James R. Berenson, Hank H. Yang, Karen Sadler, Supol G. Jarutirasarn, Robert A. Vescio, Russell Mapes, Matthew Purner, Shi-pyng Lee, Joanna Wilson, Blake Morrison, Julian Adams, David Schenkein, Regina Swift
Journal: Journal of Clinical Oncology (2006)

Bortezomib has shown synergy with melphalan in preclinical models. We assessed the safety, tolerability, and response rate in a dose-escalation study of this combination for relapsed or refractory multiple myeloma patients.Bortezomib was administered from 0.7 to 1.0 mg/m(2) on days 1, 4, 8, and 11 of a 28-day cycle for up to eight cycles. Oral melphalan was administered in escalating doses from 0.025 to 0.25 mg/kg on days 1 to 4.Thirty-five patients with relapsed or refractory myeloma were enrolled, 34 of whom were assessable for response. Dose-limiting toxicity of grade 4 neutropenia in two of six patients in the highest dose cohort led to the assignment of bortezomib 1.0 mg/m2 and melphalan 0.10 mg/kg as the maximum-tolerated dose (MTD). Responses (minimal [MR], partial [PR], or complete [CR]) occurred in 23 of 34 patients (68%), including two CRs (6%), three immunofixation-positive CRs (9%), 11 PRs (32%), and seven MRs (21%). Responses were observed in five of six assessable patients (83%) at the MTD. Median progression-free survival for all patients was 8 months (range, 2 to 18 months). Grade > or = 3 toxicities were related mostly to myelosuppression. Among the 15 patients with grade 1/2 neuropathy at baseline, it resolved during treatment in one, worsened in four, and remained stable in 10 patients. Eight other patients developed grade 1/2 neuropathy during the study.Bortezomib plus melphalan given on a 28-day schedule showed encouraging activity with manageable toxicity and represents a promising treatment for myeloma patients.
Chronobiology Impacts Response to Antihypertensive Drug Regimen in Type 2 Diabetes
Authors: Eli A. Friedman, Mary Ann Banerji
Journal: Diabetes Care (2011)

Chronobiology is the term applied to the study of how body rhythms are governed by our environment, starting with the solar system, which cycles night and day and changes one season into another (1). Bodily responses encompassed by chronobiology determine both everyday behavior and expression of illness (2). Key rhythms modulating health and disease states may be circadian (lasting about 24 h and defining sleep-awake patterns) or infradian (lasting longer than 24 h, as in monthly menstruation). Adjusting timing of medical treatment to its differing effects depending on the patient's circadian state as currently applied in nocturnal asthma (3) and arthritis (4) is called chronotherapy. Hermida et al. (5) report a prospective, randomized, open-label, blinded end point trial of how varying the time of day during which antihypertensive drugs are taken may affect cardiovascular risk in hypertensive patients with type 2 diabetes.

That chronotherapy might assist in management of hypertension was appreciated by Bartter et al. (6) in a retrospective 24-h study of a single patient with systolic and diastolic hypertension treated with hydrochlorthiazide in 1976. Availability of continuous 24-h blood pressure monitoring devices prompted a French study in 1985 suggesting that each hypertensive patient be evaluated over a full day with subsequent antihypertensive drug treatment scheduled to fit daily periods of highest pressure (7). Noting …
New Noninvasive Method for Assessment of Left Ventricular Rotation
Authors: Thomas Helle-Valle, Jonas Crosby, Thor Edvardsen, Erik Lyseggen, Brage H. Amundsen, Hans-Jørgen Smith, Boaz D. Rosen, João A.C. Lima, Hans Torp, Halfdan Ihlen, Otto A. Smiseth
Journal: Circulation (2005)

Left ventricular (LV) torsion is due to oppositely directed apical and basal rotation and has been proposed as a sensitive marker of LV function. In the present study, we introduce and validate speckle tracking echocardiography (STE) as a method for assessment of LV rotation and torsion.Apical and basal rotation by STE was measured from short-axis images by automatic frame-to-frame tracking of gray-scale speckle patterns. Rotation was calculated as the average angular displacement of 9 regions relative to the center of a best-fit circle through the same regions. As reference methods we used sonomicrometry in anesthetized dogs during baseline, dobutamine infusion, and apical ischemia, and magnetic resonance imaging (MRI) tagging in healthy humans. In dogs, the mean peak apical rotation was -3.7+/-1.2 degrees (+/-SD) and -4.1+/-1.2 degrees, and basal rotation was 1.9+/-1.5 degrees and 2.0+/-1.2 degrees by sonomicrometry and STE, respectively. Rotations by both methods increased (P<0.001) during dobutamine infusion. Apical rotation by both methods decreased during left anterior descending coronary artery occlusion (P<0.007), whereas basal rotation was unchanged. In healthy humans, apical rotation was -11.6+/-3.8 degrees and -10.9+/-3.3 degrees, and basal rotation was 4.8+/-1.7 degrees and 4.6+/-1.3 degrees by MRI tagging and STE, respectively. Torsion measurement by STE showed good correlation and agreement with sonomicrometry (r=0.94, P<0.001) and MRI (r=0.85, P<0.001).The present study demonstrates that regional LV rotation and torsion can be measured accurately by STE, suggesting a new echocardiographic approach for quantification of LV systolic function.
Practical Paediatric Respiratory Medicine: Edited by M Silverman, C L O'Callaghan. London: Arnold, 2001, pound39.50, pp 293 (paperback). ISBN 0 340 74126 0
Authors: M Everard
Journal: Thorax (2002)

It is always pleasing when a new publication devoted to respiratory disease in childhood is published. This text appears to be aimed at children's respiratory nurses and paediatric trainees, providing a grounding in many facets of paediatric …
Current concepts: scapular dyskinesis
Authors: W Ben Kibler, Aaron Sciascia
Journal: British Journal of Sports Medicine (2009)

The scapula serves many roles in order for proper shoulder function to occur. These roles include providing synchronous scapular rotation during humeral motion, serving as a stable base for rotator cuff activation and functioning as a link in the kinetic chain. Each role is vital to proper arm function and can only occur when the anatomy around the shoulder is uncompromised. The presence of bony and soft tissue injury as well as muscle weakness and inflexibility can alter the roles of the scapula and alter scapular resting position and/or dynamic motion. This altered scapular position/movement has been termed 'scapular dyskinesis'. Although it occurs in a large number of shoulder injuries, it appears that scapular dyskinesis is a non-specific response to a painful condition in the shoulder rather than a specific response to certain glenohumeral pathology. The presence or absence of scapular dyskinesis needs to be determined during the clinical examination. An examination consisting of visual inspection of the scapular position at rest and during dynamic humeral movements, along with the performance of objective posture measurements and scapular corrective maneuvers, will help the clinician ascertain the extent to which the scapula is involved in the shoulder injury. Treatment of scapular dyskinesis should begin with optimised anatomy and then progress to the restoration of dynamic scapular stability by strengthening of the scapular stabilisers utilising kinetic chain-based rehabilitation protocols.
Beneficial effects of the anti-oestrogen tamoxifen on systemic lupus erythematosus of (NZBxNZW)F1 female mice are associated with specific reduction of IgG3 autoantibodies
Authors: Z M Sthoeger
Journal: Annals of the Rheumatic Diseases (2003)

<h3>Objective.</h3> To study predictors of discordance between self-reported physician diagnosis and administrative database diagnosis of arthritis. <h3>Methods.</h3> A cohort of all veterans who utilized Veterans Integrated Service Network (VISN)-13 medical facilities were mailed a questionnaire that included patient self-report of physician diagnosis of arthritis and questions regarding demographics, functional limitation, and SF-36V (a validated version of the Medical Outcomes Study Short-Form 36). Kappa coefficient was used to assess the extent of agreement between self-report of physician diagnosis and administrative database definitions that incorporated <i>International Classification of Diseases</i> (ICD) codes and use of medications for arthritis. We identified predictors of overall discordance between self-report and administrative database diagnosis using multivariable logistic regression analyses. <h3>Results.</h3> Among 70,334 eligible veterans surveyed, 19,749 subjects had an ICD diagnosis of arthritis in the administrative database in the year prior to the survey; 34,440 answered the arthritis question and 18,464 self-reported a physician diagnosis of arthritis. Kappa coefficient showed slight to fair agreement of 0.19–0.32 between self-report and administrative database definitions of arthritis. We found significantly higher overall discordance among veterans with more comorbidities, greater age, worse functional status, lower use of outpatient and inpatient services, lower education level, and among single medical-site users. <h3>Conclusion.</h3> Low level of agreement between self-report and database diagnosis of arthritis and its significant association with patient demographic, clinical, and functional characteristics highlights the limitation of use of these strategies for identification of patients with arthritis in epidemiological studies.
A calcium-deficient diet caused decreased bone mineral density and secondary elevation of estrogen in aged male rats[mdash ]effect of menatetrenone and elcatonin
Authors: Seiya Kato, Toshiki Mano, Takako Kobayashi, Naho Yamazaki, Yumiko Himeno, Keiko Yamamoto, Mitsuyasu Itoh, Nobuhiro Harada, Akio Nagasaka
Journal: Metabolism (2002)
DNA Microarray Profiling to Identify Angiotensin-Responsive Genes in Vascular Smooth Muscle Cells
Authors: Alexandre H. Campos, Ying Zhao, Matthew J. Pollman, Gary H. Gibbons
Journal: Circulation Research (2003)

Angiotensin II (Ang II) induces changes in vessel structure by its capacity to activate genes that are coupled to signaling pathways such as extracellular signal-regulated kinase (ERK), p38, and phosphatidylinositol 3-kinase (PI3K). Using a DNA microarray containing 5088 genes and expressed sequence tags, we initially established a database of replicated experiments (n=4) to define the variances in mRNA expression in response to Ang II versus vehicle treatment. We observed a wide range of values for the coefficients of variation in a gene-specific manner. Guided by power calculations, we used statistical inference on a sufficient number of experimental replicates to minimize the number of false-negatives and define a subset of Ang II-responsive genes (P<0.05). To further characterize the molecular circuitry that couples Ang II stimulation with mRNA expression, we assessed expression profiles in the presence and absence of inhibitors of ERK, p38, and PI3K. Using two different methods of computational cluster analysis, we identified a subset of six matricellular proteins (eg, osteopontin and plasminogen activator inhibitor-1) that are coordinately upregulated by Ang II via an ERK/p38-dependent pathway. In addition, these cluster analyses identified calpactins I and II as novel Ang II-responsive genes. Given that Ang II promotes vascular lesion formation, we examined whether this matricellular gene cluster was also coordinately regulated in vivo. Indeed, we demonstrate that both calpactin I and osteopontin are upregulated in response to vascular injury. Taken together, the combined use of DNA microarrays, statistical inference, and cluster analysis identified novel, coordinately regulated Ang II-responsive genes that may mediate vascular lesion formation.
Hypothyroidism Produced by Radioactive Iodine (I <sup>131</sup> ) in the Treatment of Euthyroid Patients with Angina Pectoris and Congestive Heart Failure
Authors: HERRMAN L. BLUMGART, A. STONE FREEDBERG, GEORGE S. KURLAND
Journal: Circulation (1950)

Hypothyroidism, induced by I 131 to lessen the work of the heart, is proposed as a means of treating certain patients with angina pectoris and congestive failure who are refractory to the standard medical measures. Eighteen such patients have been treated. The period of follow-up averages thirteen months. Eight of the 13 patients with angina pectoris and 3 of 5 patients with congestive failure showed worthwhile improvement. In 6 of the 18 patients, the improvement was striking. Tentative criteria for the selection of patients, their pre- and post-treatment management, and detailed descriptions of the results are presented.
Fasting Intact Proinsulin Is a Highly Specific Predictor of Insulin Resistance in Type 2 Diabetes
Authors: Andreas Pfützner, Thomas Kunt, Cloth Hohberg, Agnes Mondok, Sabine Pahler, Thomas Konrad, Georg Lübben, Thomas Forst
Journal: Diabetes Care (2004)

OBJECTIVE—In later stages of type 2 diabetes, proinsulin and proinsulin-like molecules are secreted in increasing amounts with insulin. A recently introduced chemiluminescence assay is able to detect the uncleaved “intact” proinsulin and differentiate it from proinsulin-like molecules. This investigation explored the predictive value of intact proinsulin as an insulin resistance marker. RESEARCH DESIGN AND METHODS—In total, 48 patients with type 2 diabetes (20 women and 28 men, aged 60 ± 9 years [means ± SD], diabetes duration 5.1 ± 3.8 years, BMI 31.2 ± 4.8 kg/m2, and HbA1c 6.9 ± 1.2%) were studied by means of an intravenous glucose tolerance test and determination of fasting values of intact proinsulin, insulin, resistin, adiponectin, and glucose. Insulin resistance was determined by means of minimal model analysis (MMA) (as the gold standard) and homeostatis model assessment (HOMA). RESULTS—There was a significant correlation between intact proinsulin values and insulin resistance (MMA P &amp;lt; 0.05 and HOMA P &amp;lt; 0.01). Elevation of intact proinsulin values above the reference range (&amp;gt;10 pmmol/l) showed a very high specificity (MMA 100% and HOMA 92.9%) and a moderate sensitivity (MMA 48.6% and HOMA 47.1%) as marker for insulin resistance. Adiponectin values were slightly lower in the insulin resistant group, but no correlation to insulin resistance could be detected for resisitin in the cross-sectional design. CONCLUSIONS—Elevated intact proinsulin seems to indicate an advanced stage of β-cell exhaustion and is a highly specific marker for insulin resistance. It might be used as arbitrary marker for the therapeutic decision between secretagogue, sensitizer, or insulin therapy in type 2 diabetes.
Expiratory muscle activity and nasal expiratory pressure during reverse sniff
Authors: Tsuyoshi Ichikawa, Masanori Yokoba, Naohito Ishii, Akira Takakura, Atsuhiko Matsunaga, Masahiko Kimura, Tadashi Abe, Noriyuki Masuda, Paul Easton, Masato Katagiri
Journal: European Respiratory Journal (2012)

The evaluation of expiratory muscle strength is of clinical importance in patients with neuromuscular respiratory disease. Maximal expiratory pressure (MEP) has achieved wide acceptance as a simple non-invasive measurement of expiratory muscle strength. However, MEP measurement is difficult for neuromuscular disease patients. In this study, we measured expiratory muscle activity during reverse sniff, a maneuver akin to “blowing your nose”, and we analyzed the relationship between expiratory muscle activity and reverse sniff nasal expiratory pressure (RSNEP).  In 5 healthy subjects, mean age 21.2 yrs, weight 69.2 kg, height 176.6 cm, we inserted fine wire electrodes into transversus abdominis muscle (TA) using high-resolution ultrasound. RSNEP was measured through a catheter that occluded one nostril, while the contralateral nostril remained open. Subjects performed short, sharp, maximum and variable intensity of reverse sniff, beginning from FRC while standing. TA EMG activity was expressed as percent of maximum EMG (%EMGmax) throughout respiratory and non-respiratory maneuvers.  Mean MEP was 80.8±0.6 cmH2O. Mean maximum RSNEP was 34.9±18.7 cmH2O, and mean TA EMG activity at maximum RSNEP was 73.9±23.6 %EMGmax. TA EMG activity increased with stepwise increments in RSNEP. In every subject, the linear relationship between RSNEP and TA EMG activity was significant (r = 0.56-0.98, p  We conclude that RSNEP corresponds to the activity of the expiratory muscle transversus abdominis, and that this simple maneuver may be useful for assessment of expiratory muscle strength.  This study was approved by Kitasato university human ethics committee. This work was supported by MEXT of Japan KAKENHI (2350061).
STUDIES ON CALCIUM AND MAGNESIUM METABOLISM IN DISEASE
Authors: Frank P. Underhill, James A. Honeij, L. Jean Bogert
Journal: The Journal of Experimental Medicine (1920)

In the stabilized stage of exostosis calcium exchange differs little from that of a normal individual whether the abnormal subject is maintained upon a calcium-poor diet or upon one rich in this element. In the progressive stage of the disease calcium metabolism is markedly different from the normal in that calcium is lost from the body in large amounts when the subject is maintained upon a calcium-poor diet. This excessive elimination of calcium is by way of both the urine and feces in a normal ratio. When placed upon a calcium-rich diet calcium is retained to an extent not widely deviating from that obtained in normal subjects. A resumption to a calcium-poor diet again induces excessive calcium elimination. In the stabilized stage of exostosis magnesium excretion is two or three times greater than the intake whether the subject is maintained upon a diet poor or rich in magnesium. In the progressive stage of the disease the general type of magnesium excretion resembles that of the stabilized stage but the degree of elimination is not so marked. Magnesium added to the diet in the stabilized stage is promptly excreted. The same test applied to the progressive stage gives evidence of retention of some magnesium. The degree of retention, however, is much less than that shown by normal individuals. Absorption of both calcium and magnesium in exostosis is not inferior to that of normal subjects. The facts enumerated suggest that in the early stages of exostosis, that is during the proliferative cartilage changes, the progress of the disease may perhaps be checked by proper dietary procedure - restriction of calcium and magnesium intake.
Multicenter phase II trial of preoperative induction chemotherapy followed by chemoradiation with docetaxel and cisplatin for locally advanced esophageal carcinoma (SAKK 75/02)
Authors: T. Ruhstaller, L. Widmer, J.C. Schuller, A. Roth, V. Hess, W. Mingrone, R. von Moos, M. Borner, B.C. Pestalozzi, S. BalmerMajno, D. Köberle, L. Terraciano, A. Schnider, S. Bodis, R. Popescu
Journal: Annals of Oncology (2009)
Hematopoietic Stem Cell Transplantation&lt;subtitle&gt;A Global Perspective&lt;/subtitle&gt;
Authors: Alois Gratwohl, Helen Baldomero, Mahmoud Aljurf, Marcelo C. Pasquini, Luis Fernando Bouzas, Ayami Yoshimi, Jeff Szer, Jeff Lipton, Alvin Schwendener, Michael Gratwohl, Karl Frauendorfer, Dietger Niederwieser, Mary Horowitz, Yoshihisa Kodera, Marrow Transplantation
Journal: JAMA (2010)

Hematopoietic stem cell transplantation (HSCT) requires significant infrastructure. Little is known about HSCT use and the factors associated with it on a global level.To determine current use of HSCT to assess differences in its application and to explore associations of macroeconomic factors with transplant rates on a global level.Retrospective survey study of patients receiving allogeneic and autologous HSCTs for 2006 collected by 1327 centers in 71 participating countries of the Worldwide Network for Blood and Marrow Transplantation. The regional areas used herein are (1) the Americas (the corresponding World Health Organization regions are North and South America); (2) Asia (Southeast Asia and the Western Pacific Region, which includes Australia and New Zealand); (3) Europe (includes Turkey and Israel); and (4) the Eastern Mediterranean and Africa.Transplant rates (number of HSCTs per 10 million inhabitants) by indication, donor type, and country; description of main differences in HSCT use; and macroeconomic factors of reporting countries associated with HSCT rates.There were 50 417 first HSCTs; 21 516 allogeneic (43%) and 28 901 autologous (57%). The median HSCT rates varied between regions and countries from 48.5 (range, 2.5-505.4) in the Americas, 184 (range, 0.6-488.5) in Asia, 268.9 (range, 5.7-792.1) in Europe, and 47.7 (range, 2.8-95.3) in the Eastern Mediterranean and Africa. No HSCTs were performed in countries with less than 300,000 inhabitants, smaller than 960 km(2), or having less than US $680 gross national income per capita. Use of allogeneic or autologous HSCT, unrelated or family donors for allogeneic HSCT, and proportions of disease indications varied significantly between countries and regions. In linear regression analyses, government health care expenditures (r(2) = 77.33), HSCT team density (indicates the number of transplant teams per 1 million inhabitants; r(2) = 76.28), human development index (r(2) = 74.36), and gross national income per capita (r(2) = 74.04) showed the highest associations with HSCT rates.Hematopoietic stem cell transplantation is used for a broad spectrum of indications worldwide, but most frequently in countries with higher gross national incomes, higher governmental health care expenditures, and higher team densities.
Mitotic Infidelity and Centrosome Duplication Errors in Cells Overexpressing Tripeptidyl-Peptidase II
Authors: Vaia Stavropoulou, Jianjun Xie, Marie Henriksson, Birgitta Tomkinson, Stefan Imreh, Maria G. Masucci
Journal: Cancer Research (2005)

Abstract The oligopeptidase tripeptidyl-peptidase II (TPP II) is up-regulated Burkitt's lymphoma (BL) cells that overexpress the c-myc proto-oncogene and is required for their growth and survival. Here we show that overexpression of TPP II induces accelerated growth and resistance to apoptosis in human embryonic kidney 293 cells. This correlates with the appearance of multiple chromosomal aberrations, numerical and structural centrosome abnormalities, and multipolar cell divisions. Similar mitotic aberrations were also observed in a panel of BL lines and were suppressed, in parallel with TPP II down-regulation, upon reversion of BL-like characteristics in EBV-immortalized B lymphocytes carrying a tetracycline-regulated c-myc. Functional TPP II knockdown by small interfering RNA expression in BL cells caused the appearance of giant polynucleated cells that failed to complete cell division. Collectively, these data point to a role of TPP II in the regulation of centrosome homeostasis and mitotic fidelity suggesting that this enzyme may be a critical player in the induction and/or maintenance of genetic instability in malignant cells.