tbuckley/cabot-search huggingface dataset:
Factors Associated With Outcomes in Allogeneic Hematopoietic Cell Transplantation With Nonmyeloablative Conditioning After Failed Myeloablative Hematopoietic Cell Transplantation
Authors: Frédéric Baron, Rainer Storb, Barry E. Storer, Michael B. Maris, Dietger Niederwieser, Judith A. Shizuru, Thomas R. Chauncey, Benedetto Bruno, Stephen J. Forman, Peter A. McSweeney, Richard T. Maziarz, Michael A. Pulsipher, Edward D. Agura, James Wade, Mohamed Sorror, David G. Maloney, Brenda M. Sandmaier
Journal: Journal of Clinical Oncology (2006)

Purpose Several studies have investigated the feasibility of allogeneic hematopoietic cell transplantations (HCTs) after reduced-intensity conditioning in patients who experienced relapse after myeloablative HCT. Although most studies showed relatively low nonrelapse mortality (NRM) rates and encouraging short-term results, it has yet to be defined which patients would benefit most from these approaches. Patients and Methods We analyzed data from 147 patients with hematologic malignancies who experienced treatment failure with conventional autologous (n = 135), allogeneic (n = 10), or syngeneic (n = 2) HCT and were treated with HLA-matched related (n = 62) or unrelated (n = 85) grafts after conditioning with 2 Gy of total-body irradiation with or without fludarabine. Results Three-year probabilities of NRM, relapse, and overall survival were 32%, 48%, and 27%, respectively, for related recipients, and 28%, 44%, and 44%, respectively, for unrelated recipients. The best outcomes were observed in patients with non-Hodgkin's lymphoma, whereas patients with multiple myeloma and Hodgkin's disease had worse outcomes as a result of high incidences of relapse and progression. Being in partial remission (PR) or complete remission (CR) at HCT (P = .002) and developing chronic graft-versus-host disease (GVHD; P = .03) resulted in lower risks of relapse and progression. Factors associated with better overall survival were PR or CR (P = .01) and lack of comorbidity (P = .03) at HCT and absence of acute GVHD after HCT (P = .06). Conclusion Encouraging outcomes were seen with allogeneic HCT after nonmyeloablative conditioning in selected patients who had experienced relapse after a high-dose HCT, particularly in patients with non-Hodgkin's lymphoma. Results with unrelated grafts were comparable with results with related grafts.
Insulin receptor kinase in human skeletal muscle from obese subjects with and without noninsulin dependent diabetes.
Authors: J F Caro, M K Sinha, S M Raju, O Ittoop, W J Pories, E G Flickinger, D Meelheim, G L Dohm
Journal: Journal of Clinical Investigation (1987)

We have studied the structure and function of the insulin receptors in obese patients with and without noninsulin dependent diabetes mellitus (NIDDM) and in nonobese controls using partially purified receptors from muscle biopsies. Insulin binding was decreased in obesity due to reduced number of binding sites but no differences were observed in insulin binding between obese subjects with or without NIDDM. The structural characteristics of the receptors, as determined by affinity labeling methods and electrophoretic mobility of the beta-subunit, were not altered in obese or NIDDM compared to normal weight subjects. Furthermore, the ability of insulin to stimulate the autophosphorylation of the beta-subunit and the phosphoamino acid composition of the phosphorylated receptor were the same in all groups. However, insulin receptor kinase activity was decreased in obesity using Glu4:Tyr1 as exogenous phosphoacceptor without any appreciable additional defect when obesity was associated with NIDDM. Thus, our data are supportive of the hypothesis that in muscle of obese humans, insulin resistance is partially due to decreased insulin receptors and insulin receptor kinase activity. In NIDDM the defect(s) in muscle is probably distal to the insulin receptor kinase.
Mice lacking β3 integrins are osteosclerotic because of dysfunctional osteoclasts
Authors: Kevin P. McHugh, Kairbaan Hodivala-Dilke, Ming-Hao Zheng, Noriyuki Namba, Jonathan Lam, Deborah Novack, Xu Feng, F. Patrick Ross, Richard O. Hynes, Steven L. Teitelbaum
Journal: Journal of Clinical Investigation (2000)

Osteoclasts express the αvβ3 integrin, an adhesion receptor that has been implicated in bone resorption and that is therefore a potential therapeutic target. To assess the role of this heterodimer in skeletal development in vivo, we engineered mice in which the gene for the β3 integrin subunit was deleted. Bone marrow macrophages derived from these mutants differentiate in vitro into numerous osteoclasts, thus establishing that αvβ3 is not necessary for osteoclast recruitment. Furthermore, the closely related integrin, αvβ5, does not substitute for αvβ3 during cytokine stimulation or authentic osteoclastogenesis. β3 knockout mice, but not their heterozygous littermates, develop histologically and radiographically evident osteosclerosis with age. Despite their increased bone mass, β3-null mice contain 3.5-fold more osteoclasts than do heterozygotes. These mutant osteoclasts are, however, dysfunctional, as evidenced by their reduced ability to resorb whale dentin in vitro and the significant hypocalcemia seen in the knockout mice. The resorptive defect in β3-deficient osteoclasts may reflect absence of matrix-derived intracellular signals, since their cytoskeleton is distinctly abnormal and they fail to spread in vitro, to form actin rings ex vivo, or to form normal ruffled membranes in vivo. Thus, although it is not required for osteoclastogenesis, the integrin αvβ3 is essential for normal osteoclast function.
Pulmonary Arterial Blood Volume and Tissue Volume in Man and Dog
Authors: MARVIN A. SACKNER, NEAL ATKINS, JOSEPH GOLDBERG, NATHAN SEGEL, STEPHEN ZARZECKI, ADAM WANNER
Journal: Circulation Research (1974)

After the injection of an ethyl ether-alcohol solution above the pulmonic valve, the pulmonary arterial circulation time was determined in conscious man by an established body plethysmographic technique and in anesthetized man by a newly developed pneumotachographic method. In the anesthetized dog, estimates of pulmonary arterial circulation time determined by this new method were compared with those simultaneously determined by the plethysmographic method; agreement was good. The usefulness of applying corrective factors for the right-to-left intrapulmonary shunt and the uptake of ether gas from the alveoli into the blood while the ether gas is being evolved from the initial injection was evaluated from the dog experiments. In five humans with normal pulmonary arterial pressures, pulmonary arterial blood volume estimated by these methods was 172 ± 22 (sd) ml. Estimates of pulmonary tissue volume in both dogs and man were much larger than previously reported values determined from the tritiated water space of the lungs but more in keeping with previously published estimates of the total water content of the lungs determined at postmortem examination.
A Generalized Mechanistic Codon Model
Authors: Maryam Zaheri, Linda Dib, Nicolas Salamin
Journal: Molecular Biology and Evolution (2014)

Models of codon evolution have attracted particular interest because of their unique capabilities to detect selection forces and their high fit when applied to sequence evolution. We described here a novel approach for modeling codon evolution, which is based on Kronecker product of matrices. The 61 × 61 codon substitution rate matrix is created using Kronecker product of three 4 × 4 nucleotide substitution matrices, the equilibrium frequency of codons, and the selection rate parameter. The entities of the nucleotide substitution matrices and selection rate are considered as parameters of the model, which are optimized by maximum likelihood. Our fully mechanistic model allows the instantaneous substitution matrix between codons to be fully estimated with only 19 parameters instead of 3,721, by using the biological interdependence existing between positions within codons. We illustrate the properties of our models using computer simulations and assessed its relevance by comparing the AICc measures of our model and other models of codon evolution on simulations and a large range of empirical data sets. We show that our model fits most biological data better compared with the current codon models. Furthermore, the parameters in our model can be interpreted in a similar way as the exchangeability rates found in empirical codon models.
Secondary infestation of the pleura as a complication of intrapulmonary echinococcosis
Authors: Walid Feki, Wajdi Ketata, Najla Bahloul, Sameh Msaed, Samy Kammoun
Journal: European Respiratory Journal (2013)

Introduction   Hydatid cystic disease is caused by larvae of the Tapeworm Echinococcus. The organs most commonly affected are the liver and the lungs. Pleural involvement is rare, and usually follows the rupture of a pulmonary or hepatic cyst inside the pleural space .    Purpose   The purpose of this study was to exhibit some characteristics of secondary infestation of the pleura as a complication of intrapulmonary echinococcosis.   Materials and methods   We retrospectively reviewed the medical and radiological records of patients who had hospitalized for pulmonary hydatid disease complicated by pleural effusion at the center for Chest Diseases of Hedi Chaker hospital, Sfax, Tunisia, between 1 January 1993 and 31 December 2012.   Results   Five patients were included. There were two females and three males with a mean age of 48. The most common symptoms were cough-sputum (4 cases) and chest pain (3 cases). Chest examination revealed diminished movements over hemithorax with decreased breath sounds in all patients. The most common radiologic finding was the pleural fluid (n=4). The other findings included hydropneumothorax (n=1), air-fluid level mimicking abscess (n=2) and a round cystic opacity (n=3). All patients underwent surgical resection of the pulmonary cysts. In addition, three patients required a pleurectomy. No patient died as a result of echinococcal disease or complications from surgery.   Conclusion   Hydatid cyst rupture in the pleura should be considered in the differential diagnosis of cases with pleural effusion, empyema, pneumothorax and hydropneumothorax occurring in endemic regions. Performing the surgery without delay favorably affects postoperative morbidity and mortality.
The death of childhood
Authors: D. C. Essex
Journal: BMJ (1997)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following The death of childhood Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
ABC of practical procedures
Authors: A. Feather
Journal: Gut (2010)

Edited by Tim Nutbeam, Ron Daniels. . Published by Wiley-Blackwell, Chichester, 2010, pp 128, £25.99 (softcover). ISBN-978-1-4051-8595-0.

> It is 2033. Medical trainees and practitioners, from first year undergraduates to consultant specialists and senior general practitioners no longer need textbooks. All their learning requirements are found on the virtual web. Practical procedures and clinical examination skills are practiced on ‘virtual patients’ with instant feedback and grading of competency. Only trainees who attain a grade of ‘highly competent’ or ‘expert’ on the World Council of Medicine's virtual assessment programme are allowed to perform and hone their skills on ‘real patients, in real clinical areas’.

For those of you that feel that this may be a drug fuelled Orwellian nightmare of things to come, welcome to the teaching and learning of clinical skills in the 21st century.1 Whether this is the correct method to learn skills remains to be seen but this …
Effects of oral hyposensitization with recombinant Der f2 on immediate airway constriction in a murine allergic model
Authors: M Yasue, T Yokota, M Yuasa, Y Kajiwara, M Suko, H Okudaira
Journal: European Respiratory Journal (1998)

Recombinant Der f2 (rDer f2) has recently been developed as a promising allergen for the diagnosis and immunotherapy of house-dust mite allergy, and studies in immunology. The aim of the present study was to evaluate whether oral administration of rDer f2 could suppress an immediate allergic reaction in mice sensitized with mite allergen. We developed a murine allergic model that showed bronchoconstriction after inhalation of rDer f2, and studied the effect of oral administration of rDer f2 on the reaction. Seven week old male A/J mice were intranasally immunized with rDer f2 12 times. Sensitized mice showed anti-rDer f2 immunoglobulin (Ig)E production and immediate airway constriction after inhalation of 10 mg.mL(-1) of rDer f2, as determined by the Konzett-Rossler method. Immunized animals were divided into three groups, and fed phosphate-buffered saline (PBS), 0.1 mg.day(-1), or 1 mg.day(-1) of rDer f2 for 4 weeks, respectively. Seven days after the last feeding, the mice were examined for their immediate response. Animals fed with 1 mg.day(-1) rDer f2 showed significantly reduced bronchoconstriction after inhalation of both 2 mg.mL(-1) and 10 mg.mL(-1) of rDer f2 compared with PBS-fed mice. Similar results were obtained when we examined mice 10 weeks after the last feeding. Reactions in the 0.1 mg.day(-1) rDer f2-fed group also tended to decrease in comparison with PBS-fed animals. Plasma anti-rDer f2 IgE, IgG1, IgG2a, and IgG2b levels were not changed by feeding with rDer f2. We conclude that recombinant Der f2 exhibits both sensitizing and hyposensitizing activities in mice. rDer f2 may be useful in immunotherapy and diagnosis of house-dust mite allergy.
High prevalence of arthropathy in HTLV-I carriers on a Japanese island.
Authors: S Motokawa, T Hasunuma, K Tajima, A M Krieg, S Ito, K Iwasaki, K Nishioka
Journal: Annals of the Rheumatic Diseases (1996)

OBJECTIVE: To determine the aetiological relationship between human T cell leukaemia virus type-I (HTLV-I) and arthritis, by performing an epidemiological study of the inhabitants of Tsushima, an island northwest of the main island of Kyushu, Japan, which is an endemic area of HTLV-I. METHODS: A total of 7087 people underwent an annual health check, and those with arthropathy had further physical and radiological examinations by rheumatologists. The presence of HTLV-I antibody was determined by the particle agglutinin method, and integration of the proviral DNA in peripheral lymphocytes was confirmed by polymerase chain reaction. RESULTS: HTLV-I was positive in 26.1% of inhabitants; the incidence increased to 37.0% in patients with symptoms of polyarthritis. The prevalence of rheumatoid arthritis (RA) was significantly different between HTLV-I carriers (0.56%) and non-carriers (0.31%). The stage of bone destruction in HTLV-I carriers with articular symptoms was milder than that in RA patients without HTLV-I. The relative risk of HTLV-I infection for polyarthritis was 1.66 (p &lt; 0.05). CONCLUSION: This is the first epidemiological report clarifying the association between HTLV-I and polyarthritis. Our results suggest that this viral infection has a relationship to RA.
Response to Comment on: Black et al. The Relative Contribution of Prepregnancy Overweight and Obesity, Gestational Weight Gain, and IADPSG-Defined Gestational Diabetes Mellitus to Fetal Overgrowth. Diabetes Care 2013;36:56–62
Authors: Mary Helen Black, David A. Sacks, Anny H. Xiang, Jean M. Lawrence
Journal: Diabetes Care (2013)

We thank McIntyre and Catalano (1) for their interest in our article (2). In this study, we examined the relative effects of prepregnancy overweight/obesity, excess gestational weight gain, and IADPSG-defined gestational diabetes mellitus (GDM) on fetal overgrowth and other adverse outcomes, in a sample of 9,835 women who had a 2-h 75-g oral glucose tolerance test and were not treated with diet, exercise, or antidiabetic medications during pregnancy. Our analysis revealed that the majority (75%) of GDM women were overweight or obese at the start of pregnancy, and 21.6% of large-for-gestational-age (LGA) infants were attributable to overweight/obesity among women who never developed GDM. We also found that the effects of overweight/obesity and GDM …
Clinical, Agricultural, and Evolutionary Biology of Myostatin: A Comparative Review
Authors: Buel D. Rodgers, Dilip K. Garikipati
Journal: Endocrine Reviews (2008)

The discovery of myostatin and our introduction to the "Mighty Mouse" over a decade ago spurred both basic and applied research and impacted popular culture as well. The myostatin-null genotype produces "double muscling" in mice and livestock and was recently described in a child. The field's rapid growth is by no means surprising considering the potential benefits of enhancing muscle growth in clinical and agricultural settings. Indeed, several recent studies suggest that blocking myostatin's inhibitory effects could improve the clinical treatment of several muscle growth disorders, whereas comparative studies suggest that these actions are at least partly conserved. Thus, neutralizing myostatin's effects could also have agricultural significance. Extrapolating between studies that use different vertebrate models, particularly fish and mammals, is somewhat confusing because whole genome duplication events have resulted in the production and retention of up to four unique myostatin genes in some fish species. Such comparisons, however, suggest that myostatin's actions may not be limited to skeletal muscle per se, but may additionally influence other tissues including cardiac muscle, adipocytes, and the brain. Thus, therapeutic intervention in the clinic or on the farm must consider the potential of alternative side effects that could impact these or other tissues. In addition, the presence of multiple and actively diversifying myostatin genes in most fish species provides a unique opportunity to study adaptive molecular evolution. It may also provide insight into myostatin's nonmuscle actions as results from these and other comparative studies gain visibility in biomedical fields.
Risk factors of frequent exacerbations in difficult-to-treat asthma
Authors: A. ten Brinke, P. J. Sterk, A. A. M. Masclee, P. Spinhoven, J. T. Schmidt, A. H. Zwinderman, K. F. Rabe, E. H. Bel
Journal: European Respiratory Journal (2005)

Recurrent exacerbations are a major cause of morbidity and medical expenditure in patients with asthma. Various exogenous and endogenous factors are thought to influence the level of asthma control, but systematical data on the involvement of these factors in the recurrence of asthma exacerbations are scarce. In this study, 13 clinical and environmental factors potentially associated with recurrent exacerbations were investigated in 136 patients with difficult-to-treat asthma. Patients with more than three severe exacerbations (n = 39) in the previous year were compared with those with only one exacerbation per year (n = 24). A systematic diagnostic protocol was used to assess 13 potential risk factors. Factors significantly associated with frequent exacerbations included: severe nasal sinus disease (adjusted odds ratio (OR) 3.7); gastro-oesophageal reflux (OR 4.9); recurrent respiratory infections (OR 6.9); psychological dysfunctioning (OR 10.8); and obstructive sleep apnoea (OR 3.4). Severe chronic sinus disease and psychological dysfunctioning were the only independently associated factors (adjusted OR 5.5 and 11.7, respectively). All patients with frequent exacerbations exhibited at least one of these five factors, whilst 52% showed three or more factors. In conclusion, the results show that recurrent exacerbations in asthma are associated with specific co-morbid factors that are easy to detect and that are treatable. Therapeutic interventions aimed at correcting these factors are likely to reduce morbidity and medical expenditure in these patients.
Diagnosing ectopic pregnancy and current concepts in the management of pregnancy of unknown location
Authors: E. Kirk, C. Bottomley, T. Bourne
Journal: Human Reproduction Update (2013)

A diagnosis of ectopic pregnancy (EP) is primarily achieved using transvaginal ultrasonography (TVS). Pregnancy of unknown location (PUL) is the term used to categorize a pregnancy in a woman with a positive pregnancy test when no pregnancy has been visualized using TVS. This review appraises current tools for the diagnosis of EP, describes the diagnostic criteria for non-tubal EP and reviews the literature on the clinical management of PUL. We performed a targeted search using the PubMed database. All articles published in the English language from January 1984 to March 2013 were screened for eligibility. Using TVS to diagnose EP is highly sensitive (87–99%) and specific (94–99.9%). Variations exist in the criteria used for ultrasound diagnosis. Studies report that between 5 and 42% of women seen for ultrasound assessment with a positive pregnancy test have a PUL. For PUL, measurements of serum human chorionic gonadotrophin (hCG) and progesterone are used to predict pregnancy viability and therefore give an indication of the risk of an EP. Only 6–20% of PUL are subsequently diagnosed with EP. Non-tubal EPs are relatively uncommon, difficult to diagnose and result in disproportionate morbidity and mortality. Access to expertise and equipment for high-quality TVS means the majority of women with EP in developed countries can be diagnosed rapidly and accurately. Identifying PUL, which are low risk and therefore requiring less follow-up, finding better serum markers for EP and safely identifying women who do not require intervention for EP are the current diagnostic challenges.
Implantable Cardioverter-Defibrillator Shocks
Authors: Ryan T. Borne, Paul D. Varosy, Frederick A. Masoudi
Journal: JAMA Internal Medicine (2013)

Importance: Implantable cardioverter-defibrillators (ICDs) have revolutionized the approach to the prevention of sudden cardiac death and are commonly used in a wide range of high-risk patients, including the large population of patients with severe left ventricular systolic dysfunction.The benefit of these devices derives from their therapies, including both antitachycardia pacing and high-energy shocks.However, although these therapies may be life saving, devices can also deliver inappropriate shocks.Objective: To review ICD therapies (shocks and antitachycardia pacing), their effects on health outcomes, and current methods to reduce these therapies.Evidence Review: We reviewed clinical evidence on ICD shocks and reference lists of retrieved articles.We also examined literature about the methods of reducing ICD therapy.Findings: Both appropriate and inappropriate ICD shocks are common and are associated with an adverse effect on health outcomes, quality of life, and mortality.Several methods are available to reduce the risk of inappropriate ICD therapies.Conclusions and Relevance: Implantable cardioverterdefibrillators reduce the risk of sudden cardiac death and prolong life in selected populations; however, many patients will receive an ICD shock, either appropriate or inappropriate.It is imperative that patients be counseled regarding this risk and adverse outcomes associated with shocks.Reduction of ICD shock should be individualized to ensure that patients receiving these devices experience the maximal benefits of therapy while minimizing the adverse consequences.