tbuckley/cabot-search huggingface dataset:
Respiratory Muscle Testing
Authors: Frédéric Nicot, Nicholas Hart, Véronique Forin, Michèle Boulé, Annick Clément, Michael I. Polkey, Frédéric Lofaso, Brigitte Fauroux
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Rationale: Data on respiratory muscle performance in children with neuromuscular disorders are limited.Objectives: The aim of this study was to assess respiratory muscle strength by volitional and nonvolitional tests and to compare these tests with forced vital capacity.Methods: Inspiratory muscle strength was assessed by measuring transdiaphragmatic and esophageal pressures generated during volitional and nonvolitional maneuvers, whereas expiratory muscle strength was assessed by measuring the gastric pressure generated during a cough maneuver. Lung volumes were assessed by measuring forced vital capacity.Measurements and Main Results: Forty-one patients with Duchenne muscular dystrophy (n = 20), spinal amyotrophy (n = 8), and congenital myopathy (n = 13) were included, aged 2 to 18 yr. All the patients were able to perform the sniff and the cough maneuver. Sniff transdiaphragmatic pressure decreased with age in Duchenne patients, whereas it increased with age in patients with spinal amyotrophy and congenital myopathy. Magnetic stimulation of the phrenic nerves was obtained in all patients. Twenty-five (61%) patients were able to perform forced vital capacity. In the three groups of patients, a positive correlation was observed between volitional, assessed by the sniff maneuver, and nonvolitional respiratory muscle tests, assessed by the magnetic stimulation of the phrenic nerves. Also, forced vital capacity correlated with sniff transdiaphragmatic pressure and cough gastric pressure.Conclusions: Volitional respiratory muscle tests correlated with nonvolitional tests and with forced vital capacity. Simple volitional respiratory muscle tests constitute a valuable tool for the assessment of respiratory muscle strength in young patients with neuromuscular disorders.
Kenneth Archibald Edmund Spence
Authors: J. P. M. Peterson
Journal: BMJ (2014)

After starting at Guy’s in 1938, Kenneth Archibald Edmund Spence decided to put his medical training on hold to join the army at the outbreak of war in 1939, serving in the 14th Antitank Regiment Royal Artillery in north Africa, Italy, and later Palestine, as mentioned in Dispatches .

He …
Selenium Supplementation and Secondary Prevention of Nonmelanoma Skin Cancer in a Randomized Trial
Authors: A. J. Duffield-Lillico
Journal: JNCI Journal of the National Cancer Institute (2003)

The Nutritional Prevention of Cancer Trial was a double-blind, randomized, placebo-controlled clinical trial designed to test whether selenium as selenized yeast (200 microg daily) could prevent nonmelanoma skin cancer among 1312 patients from the Eastern United States who had previously had this disease. Results from September 15, 1983, through December 31, 1993, showed no association between treatment and the incidence of basal and squamous cell carcinomas of the skin. This report summarizes the entire blinded treatment period, which ended on January 31, 1996. The association between treatment and time to first nonmelanoma skin cancer diagnosis and between treatment and time to multiple skin tumors overall and within subgroups, defined by baseline characteristics, was evaluated. Although results through the entire blinded period continued to show that selenium supplementation was not statistically significantly associated with the risk of basal cell carcinoma (hazard ratio [HR] = 1.09, 95% confidence interval [CI] = 0.94 to 1.26), selenium supplementation was associated with statistically significantly elevated risk of squamous cell carcinoma (HR = 1.25, 95% CI = 1.03 to 1.51) and of total nonmelanoma skin cancer (HR = 1.17, 95% CI = 1.02 to 1.34). Results from the Nutritional Prevention of Cancer Trial conducted among individuals at high risk of nonmelanoma skin cancer continue to demonstrate that selenium supplementation is ineffective at preventing basal cell carcinoma and that it increases the risk of squamous cell carcinoma and total nonmelanoma skin cancer.
Detection of chromosomes tagged with green fluorescent protein in live Arabidopsis thaliana plants
Authors: Naohiro Kato, Eric Lam
Journal: Genome biology (2001)

Structural and dynamic studies of chromosomes tagged with green fluorescent protein (GFP) in yeast and cultured animal cells have revealed some surprises. Although this technology can be very powerful, only a few studies using this approach with developed multicellular systems have been reported for the study of chromatin behavior in situ.We established vectors and conditions to visualize tagged loci stably inserted in the Arabidopsis genome via GFP fused to a bacterial DNA-binding protein. Using this system, three-dimensional coordinates for tagged loci within nuclei from cells of a live plant can be directly determined with concomitant visualization of the position of the nucleolus. Chromosome polyploidization in epidermal cells at the elongation zone of the root in transgenic plants can be visualized in situ using this technique.We have established that GFP fusion with DNA-binding proteins can be used in conjunction with concatameric binding-site arrays to track genomic loci in living Arabidopsis plants. It should now be feasible to study the mechanisms of organization and dynamics of chromatin in specific cell types during various times of plant development, taking advantage of the well developed genetic systems and resources available for Arabidopsis.
The fluidity of liver plasma membranes from patients with different types of liver injury
Authors: Amador Schuller, José A. Solis-Herruzo, Jorge Moscat, J. C. Fernandez-Checa, Angel M. Municio
Journal: Hepatology (1986)

The physical properties of cell membranes play an important role in cellular homeostasis. Previous studies with animal models have shown that the hepatocyte membrane fluidity has important effects in cellular function. In order to further investigate the relationship between physical properties of membranes and liver disease, the present study was performed. Twenty-nine patients with different degrees of liver injury and 10 control individuals were studied. A lower membrane fluidity-as assessed by diphenylhexatriene fluorescence polarization-was observed in membrane preparations from patients, as compared to controls. These alterations are positively correlated with the severity of liver damage and could be accounted for by a higher cholesterol content of patients' membrane preparations.
Intravascular Ultrasound Assessment of Ulcerated Ruptured Plaques
Authors: Kenichi Fujii, Yoshio Kobayashi, Gary S. Mintz, Hideo Takebayashi, George Dangas, Issam Moussa, Roxana Mehran, Alexandra J. Lansky, Edward Kreps, Michael Collins, Antonio Colombo, Gregg W. Stone, Martin B. Leon, Jeffrey W. Moses
Journal: Circulation (2003)

It is not clear why some plaque ruptures lead to acute coronary syndromes (ACS) but others do not.We analyzed 80 plaque ruptures in 74 patients and compared culprit lesions of ACS patients with nonculprit lesions of ACS patients and lesions of non-ACS patients; both culprit and nonculprit plaque ruptures were studied in 6 of 54 ACS patients. Intravascular ultrasound findings suggesting thrombus were observed more frequently in culprit lesions of ACS patients (n=35) compared with nonculprit lesions of ACS patients (n=19) and lesions of non-ACS patients (n=26): 60% versus 32% versus 8% (P<0.001). At the minimal lumen site, smaller lumen areas (3.3+/-1.5 versus 5.4+/-2.6 versus 6.1+/-2.0 mm2, P<0.001) and greater area stenosis (61+/-15% versus 50+/-14% versus 46+/-18%, P=0.002) and plaque burden (80+/-8% versus 71+/-8% versus 69+/-10%, P<0.001) were observed in culprit lesions of ACS patients compared with nonculprit lesions of ACS patients and lesions of non-ACS patients. Lesions were longer (18.7+/-6.4 versus 154.9+/-6.1 versus 12.0+/-4.9 mm, P<0.001) and rupture site remodeling indices were greater (1.26+/-0.21 versus 1.24+/-0.21 versus 1.09+/-0.05, P=0.002). Independent predictors of culprit plaque ruptures in ACS patients were smaller minimum lumen areas (P=0.02) and presence of thrombus (P=0.01).Ruptured plaques in culprit lesions of ACS patients have smaller lumens; greater plaque burdens, area stenosis, and remodeling indices; and more thrombus. Plaque rupture itself does not lead to symptoms. The association of plaque rupture with a smaller lumen area and/or thrombus formation causes lumen compromise and leads to symptoms.
Effect of task familiarisation on distribution of energy during a 2000 m cycling time trial
Authors: J Corbett, M J Barwood, K Parkhouse
Journal: British Journal of Sports Medicine (2009)

To investigate the effect of task familiarisation on the spontaneous pattern of energy expenditure during a series of 2000 m cycling time trials (TTs).Nine trained males completed three 2000 m TTs on a Velotron cycling ergometer. To examine pacing strategy, the data were assigned to 250 m "bins," with the pattern of aerobic and anaerobic energy expenditure calculated from total work accomplished and gas-exchange data.There were no significant differences between trials in performance times (191.4 (SD 4.3), 189.4 (4.6), 190.1 (5.6) s), total aerobic (58.3 (2.7), 58.4 (3.1), 58.0 (3.4) kJ) and total anaerobic energy expenditure (16.4 (3.3), 17.3 (2.8), 16.5 (3.1) kJ). Pacing strategy in the second and third TT differed from the first TT in that a lower power output was adopted during the first 500 m, enabling a higher power output during the final 750 m of the TT. This adjustment in the pattern of energy expenditure was mediated by an alteration in the pattern of anaerobic energy expenditure, which paralleled changes in total energy expenditure. Furthermore, participants retained an anaerobic energy "reserve" enabling an end-spurt during the second and third trials.Small modifications to the pacing strategy are made following a single bout of exercise, primarily by altering the rate of anaerobic energy expenditure. This may have served to prevent critical metabolic disturbances. The alteration in pacing strategy following the first exercise bout is compatible with a complex intelligent regulatory system.
The Pre-Flexnerian Reports: Mark Twain's Criticism of Medicine in the United States
Authors: Patrick K. Ober
Journal: Annals of Internal Medicine (1997)

By the time Mark Twain was born, in 1835, the political forces of Jacksonian democracy had created an era of unregulated medical practice in the United States.Licensure laws were almost nonexistent, and any citizen could practice medicine. Regular ("allopathic") Medicine was competing with at least two dozen other sects, including homeopathic, botanical, and hydropathic medicine. Although allopathy presented itself as the "scientific" branch of medicine and proclaimed the practices of the other sects to be "quackery," its therapies were aggressive and toxic and had no proven advantage over the treatments used by competitors. Through the efforts of the American Medical Association (AMA), allopathic medicine eliminated its competition by promoting the reestablishment of licensure laws in the late 1800s. In a continuation of the same endeavor, the AMA sought to identify weak and inadequate medical schools and commissioned Abraham Flexner to write the famous Flexner report of 1910 (the year of Mark Twain's death). Twain, an insightful political observed and social critic who was familiar with the competing medical systems and the medical politics of the 19th century, questioned the wisdom of limiting patients' medical options.He doubted the competence and intentions of physicians as a group even as he maintained confidence in the abilities of his own physicians. He was critical of the empirical medical practices used during his youth, but he saw hope in the new scientific orientation of medicine in the early 20th century. Twain's commentaries provide a unique perspective on pre-Flexnerian medicine in the United States.
Validation of GAP score in Danish patients diagnosed with idiopathic pulmonary fibrosis
Authors: Charlotte Hyldgaard, Ole Hilberg, Elisabeth Bendstrup
Journal: European Respiratory Journal (2013)

Background  A simple clinical prediction model for mortality in idiopathic pulmonary fibrosis (the GAP model) has recently been published (Ley et al, Ann Int Med 2012). The aim of this study was to test the validity of the GAP model in a Danish IPF cohort.  Methods  Included were consecutive patients diagnosed with idiopathic pulmonary fibrosis and a first visit to our department between 2003 and 2009. All diagnoses were re-evaluated according to the 2011 ATS/ERS/JRS/ALAT guidelines. Gender, age and physiology (diffusion capacity of carbon monoxide and forced vital capacity) were used as predictor variables according to the GAP model. Male gender, age>65 years, FVC  Results  A total of 115 patients were included. Mean age was 67 years and 80% were smokers. The GAP model separated the cohort into three subgroups of patients, GAP stage I: n=37, stage II: n=55, stage III: n=23. The one-year mortality was 5.5% in stage I, 24% in stage II and 54% in stage III. Three-year mortality was 20% in stage I, 50% in stage II and 91 % in stage III. The survival difference between groups was highly statistically significant (p  Conclusion  In this Danish IPF cohort, the GAP model could be used as a simple and valid predictor of survival. Mortality was comparable to that of the derivation cohort, although slightly higher in stages II and III.
The High-Affinity CXCR4 Antagonist BKT140 Is Safe and Induces a Robust Mobilization of Human CD34+ Cells in Patients with Multiple Myeloma
Authors: Amnon Peled, Michal Abraham, Irit Avivi, Jacob M. Rowe, Katia Beider, Hanna Wald, Lena Tiomkin, Lena Ribakovsky, Yossi Riback, Yaron Ramati, Sigal Aviel, Eithan Galun, Howard Laurence Shaw, Orly Eizenberg, Izhar Hardan, Avichai Shimoni, Arnon Nagler
Journal: Clinical Cancer Research (2013)

Abstract Purpose: CXCR4 plays an important role in the retention of stem cells within the bone marrow. BKT140 (4F-benzoyl-TN14003) is a 14-residue bio stable synthetic peptide, which binds CXCR4 with a greater affinity compared with plerixafor (4 vs. 84 nmol/L). Studies in mice demonstrated the efficient and superior mobilization and transplantation of stem cells collected with GCSF-BKT140, compared with those obtained when using stem cells obtained with each one of these mobilizing agent alone. These results have served as a platform for the present clinical phase I study. Experimental Design: Eighteen patients with multiple myeloma who were preparing for their first autologous stem cell transplantation were included. Patients received a standard multiple myeloma mobilization regimen, consisting of 3 to 4 g/m2 cyclophosphamide (day 0), followed by granulocyte colony—stimulating factor (G-CSF) at 5 μg/kg/d starting on day 5 and administered between 8 and 10 pm until the end of stem cell collection. A single injection of BKT140 (0.006, 0.03, 0.1, 0.3, and 0.9 mg/kg) was administered subcutaneously on day 10 in the early morning, followed by G-CSF 12 hours later. Results: BKT140 was well tolerated at all concentrations, and none of the patients developed grade 3 and 4 toxicity. A single administration of BKT140 at the highest dose, 0.9 mg/kg, resulted in a robust mobilization and collection of CD34+ cells (20.6 ± 6.9 × 106/kg), which were obtained through a single apheresis. All transplanted patients received ∼5.3 × 106 CD34+ cells/kg, which rapidly engrafted (n = 17). The median time to neutrophil and platelet recovery was 12 and 14 days, respectively, at the highest dose (0.9 mg/kg). Conclusions: When combined with G-CSF, BKT140 is a safe and efficient stem cell mobilizer that enabled the collection of a high number of CD34+ cells in 1 and 2 aphaeresis procedures, resulting in successful engraftment. Clin Cancer Res; 20(2); 469–79. ©2013 AACR.
Radiotherapy Decreases Vascular Density and Causes Hypoxia with Macrophage Aggregation in TRAMP-C1 Prostate Tumors
Authors: Fang-Hsin Chen, Chi-Shiun Chiang, Chun-Chieh Wang, Chien-Sheng Tsai, Shih-Ming Jung, Chung-Chi Lee, William H. McBride, Ji-Hong Hong
Journal: Clinical Cancer Research (2009)

To investigate how single or fractionated doses of radiation change the microenvironment in transgenic adenocarcinoma of the mouse prostate (TRAMP)-C1 tumors with respect to vascularity, hypoxia, and macrophage infiltrates.Murine prostate TRAMP-C1 tumors were grown in C57BL/6J mice to 4 mm tumor diameter and were irradiated with either 25 Gy in a single dose or 60 Gy in 15 fractions. Changes in vascularity, hypoxia, and macrophage infiltrates were assessed by immunohistochemistry and molecular assays.Tumor growth was delayed for 1 week after both radiation schedules. Tumor microvascular density (MVD) progressively decreased over a 3-week period to nadirs of 25% and 40% of unirradiated tumors for single or fractionated treatment, respectively. In accord with the decrease in MVDs, mRNA levels of endothelial markers, such as CD31, endoglin, and TIE, decreased over the same time period after irradiation. Central dilated vessels developed surrounded by avascularized hypoxic regions that became infiltrated with aggregates of CD68+ tumor-associated macrophages, reaching a maximum at 3 weeks after irradiation. Necrotic regions decreased and were more dispersed.Irradiation of TRAMP-C1 tumors with either single or fractionated doses decreases MVD, leading to the development of disperse chronic hypoxic regions, which are infiltrated with CD68+ tumor-associated macrophages. Approaches to interfere in the development of these effects are promising strategies to enhance the efficacy of cancer radiotherapy.
Techniques to facilitate ERCP with a conventional endoscope in patients with previous pancreatoduodenectomy
Authors: M. Matsushita, H. Takakuwa, K. Uchida, A. Nishio, K. Okazaki
Journal: Endoscopy (2009)

There is little guidance on the performance of endoscopic retrograde cholangiopancreatography (ERCP) in patients with previous pancreatoduodenectomy. We reviewed techniques for ERCP with a conventional endoscope and assessed its value in 10 patients with previous pancreatoduodenectomy (15 ERCPs). After exploration of the surgical reconstruction, we used a front-viewing endoscope, and we used a small firm pillow under the abdomen and hand compression for preventing loop formation. Successful insertion to the ductal anastomoses and biliary cannulation were achieved in 13 / 15 procedures (87 %). In 6 procedures where we attempted pancreatic cannulation, we could not identify the pancreatojejunostomy, but after spraying contrast around the suspected location of the ductal anastomosis we obtained a pancreatogram in 4 / 6 procedures (67 %). Endoscopic biliary interventions were successful in 6 / 7 procedures (86 %). No complications were encountered. Use of appropriate techniques makes ERCP with a conventional endoscope feasible, effective, and safe in patients with previous pancreatoduodenectomy. Endoscopic therapy can be performed successfully in the bile duct, but has limited value regarding the pancreatic duct.
Genetically corrected iPSCs as cell therapy for recessive dystrophic epidermolysis bullosa
Authors: Daniel Wenzel, Jonathan Bayerl, Alexander Nyström, Leena Bruckner-Tuderman, Arabella Meixner, Josef M. Penninger
Journal: Science Translational Medicine (2014)

iPSCs derived from fibroblasts with mutant type VII collagen were genetically corrected and used as cell therapy in mice with recessive dystrophic epidermolysis bullosa.
The contribution of NZW genes to lupus-like disease in (NZB x NZW)F1 mice.
Authors: B L Kotzin, E Palmer
Journal: The Journal of Experimental Medicine (1987)

Unlike parental NZB or NZW mice, (NZB X NZW)F1 mice exhibit a lupus-like disease characterized by high serum levels of IgG antinuclear antibodies and a fatal immune-complex glomerulonephritis. At least three unlinked gene loci can be distinguished in NZW mice that conceivably contribute to a T cell-dependent autoimmune disease, including the MHC (H-2z) and the T cell receptor alpha and beta chain gene complexes. We undertook an (NZB X NZW)F1 X NZB backcross to determine the relative contribution of these NZW genes to lupus-like renal disease and autoantibody production in F1 mice. The incidence of severe renal disease and elevated levels of IgG antibodies to dsDNA and histone in the backcross mice was approximately half of that observed in (NZB X NZW)F1 mice. Furthermore, there was a strong correlation between the presence of the NZW H-2z haplotype and lupus-like disease in backcross mice. Approximately 90% of backcross mice with disease carried the NZW H-2z locus compared with 16% of mice without disease; nearly 90% of H-2d/z mice expressed severe autoimmune disease. In contrast, no association was apparent between the presence of the NZW T cell receptor alpha chain gene complex or beta chain gene complex and severe renal disease or autoantibody production. Thus, the NZW MHC or gene(s) linked to this locus appear to be the only dominant NZW genetic contribution to F1 disease.
Proliferative compartment deregulation in the non-neoplastic colonic epithelium of familial adenomatous polyposis.
Authors: S J Mills, N A Shepherd, P A Hall, A Hastings, J C Mathers, A Gunn
Journal: Gut (1995)

Previous work has shown abnormalities in the proliferative activity of the colorectal mucosa in familial adenomatous polyposis (FAP). Some doubts remain about the validity of these findings because of difficulties in excluding adenomatous crypts, particularly in methods using tritiated thymidine, bromodeoxyuridine, and ornithine decarboxylase. The proliferative activity of the epithelium in colonic resections from 20 FAP patients was compared with that of age, sex, and site matched controls using a new monoclonal antibody MIB1 to assay the expression of Ki-67 antigen in routinely processed tissue. The labelling indices were very similar in the polyposis and control cases (25.5 (1.4)% and 26.7 (1.7)% respectively) but analysis of the distribution of labelled cells showed a significant shift of the proliferative compartment towards the luminal surface in the FAP group. Specifically, the labelling index was lower in the basal fifth of the polyposis crypts and higher in the two fifths at the luminal surface. These results show that analysis of proliferative activity in FAP is now achievable in routine histological material and indicate deregulation of proliferative control in the FAP colonic crypt. This may form a useful diagnostic adjunct to standard clinical and molecular genetic techniques, particularly in view of the current interest in dietary and pharmacological intervention in sporadic colorectal carcinoma.