tbuckley/cabot-search huggingface dataset:
Perfecting the Craft
Authors: Fintan R. Steele
Journal: Molecular Therapy (2000)

Overlooking the Hudson River in far upper west Manhattan is a unique museum called The Cloisters. Composed of walls, columns, and courtyards reassembled from several old monasteries and convents from Europe, this imposing edifice contains the Unicorn Tapestries, arguably the finest extant specimens of Western civilization's weaving arts. Each tapestry tells a chapter of the story of the capture of the unicorn, speaking not in sound but in vision. Yet the true glory of these works lies not in the story told, nor even in the symbolism evoked, but in the intricate work that rendered countless different colored threads into such achingly beautiful cloth. Close examination of even the smallest part of one tapestry demonstrates how impossible the whole piece would be without the contribution of each thread, each knot. The Unicorn Tapestries are the ultimate triumph of the weaver's art, requiring not only the expertise of the tapestries’ immediate artisans, but also generations of contributions to perfection of the craft. Although most people who view the tapestries see only the final story, the discerning viewer sees the sweat and skill of the weavers. Although some may find it a bit of a stretch, I was reminded of the Unicorn Tapestries during last month's ASGT meeting. Medicine is truly more of an art than a science, and gene therapy researchers and practitioners are still at the stage of busily gathering up threads, selecting some and rejecting others. It stuck me that each presentation made was, in truth, a contribution to the eventual success of gene therapy. Every individual attending had a sense of what the final picture should be, and everyone also had at least one “thread” or one new “knot” which he or she believed would contribute to its completion. However, not every piece will fit, nor will each accepted piece contribute equally to the eventual success of gene therapy. Whether rejected or accepted, each does play a role in advancing the field. Despite gene therapy's early days, we can point to whole tapestries that are emerging, such as the work of Alain Fischer and his co-workers in treating SCID infants or the collaborative venture of Kathy High and Mark Kay and their co-workers in treating hemophilia. However, these stories can only be considered the success of “gene therapy” on one level. It is clear that ASGT is held together less by the notion of establishing an entire new discipline of biomedicine than by a shared devotion to perfecting the craft of gene therapy to weave new and different stories of biomedical triumph over disease. It is likely that someday there will be no field of gene therapy per se, but rather a set of exquisite therapeutic interventions finely tuned and differentially selected for human medical needs. To the casual observer, these will be merely further stories of the success of modern medicine, but to the discerning eye, the real credit will go to the artists who are even now—as the ASGT meeting demonstrated—working hard to perfect their craft.
Secretory Leukocyte Protease Inhibitor Suppresses the Inflammation and Joint Damage of Bacterial Cell Wall–Induced Arthritis
Authors: Xiao-yu Song, Li Zeng, Wenwen Jin, John Thompson, Diane E. Mizel, Ke-jian Lei, R.C. Billinghurst, A. Robin Poole, Sharon M. Wahl
Journal: The Journal of Experimental Medicine (1999)

Disruption of the balance between proteases and protease inhibitors is often associated with pathologic tissue destruction. To explore the therapeutic potential of secretory leukocyte protease inhibitor (SLPI) in erosive joint diseases, we cloned, sequenced, and expressed active rat SLPI, which shares the protease-reactive site found in human SLPI. In a rat streptococcal cell wall (SCW)-induced model of inflammatory erosive polyarthritis, endogenous SLPI was unexpectedly upregulated at both mRNA and protein levels in inflamed joint tissues. Systemic delivery of purified recombinant rat SLPI inhibited joint inflammation and cartilage and bone destruction. Inflammatory pathways as reflected by circulating tumor necrosis factor α and nuclear factor κB activation and cartilage resorption detected by circulating levels of type II collagen collagenase-generated cleavage products were all diminished by SLPI treatment in acute and chronic arthritis, indicating that the action of SLPI may extend beyond inhibition of serine proteases.
Efficacy and Safety of the Oral Neuraminidase Inhibitor Oseltamivir in Treating Acute Influenza
Authors: John J. Treanor, Frederick G. Hayden, Peter S. Vrooman, Rick Barbarash, Robert Bettis, Dennis Riff, Sudeep Singh, Nelson Kinnersley, Penelope Ward, Roger G. Mills, None for the US Oral Neuraminidase Study Group
Journal: JAMA (2000)

Previous studies have shown oseltamivir, a neuraminidase inhibitor, to be effective in preventing influenza and treating experimental influenza.To evaluate the efficacy and safety of oseltamivir in the treatment of naturally acquired influenza infection.Randomized, placebo-controlled, double-blind study conducted January through March 1998.Sixty primary care and university health centers throughout the United States.A total of 629 healthy nonimmunized adults aged 18 to 65 years with febrile respiratory illness of no more than 36 hours' duration with temperature of 38 degrees C or more plus at least 1 respiratory symptom and 1 constitutional symptom.Individuals were randomized to 1 of 3 treatment groups with identical appearing pills: oral oseltamivir phosphate, 75 mg twice daily (n = 211) or 150 mg (n = 209) twice daily, or placebo (n = 209).Duration and severity of illness in individuals infected with influenza.Two individuals withdrew before receiving medication and were excluded from further analyses. A total of 374 individuals (59.6%) were infected with influenza. Their duration of illness was reduced by more than 30% with both oseltamivir, 75 mg twice daily (median, 71.5 hours; P < .001), and oseltamivir, 150 mg twice daily (median, 69.9 hours; P = .006), compared with placebo (median, 103.3 hours). Severity of illness was reduced by 38% (median score, 597 score-hours; P < .001) with oseltamivir, 75 mg twice daily, and by 35% (median score, 626 score-hours; P < .001) with oseltamivir, 150 mg twice daily, vs placebo (median score, 963 score-hours). Oseltamivir treatment reduced the duration of fever and oseltamivir recipients returned to usual activities 2 to 3 days earlier than placebo recipients (P < or = .05). Secondary complications such as bronchitis and sinusitis occurred in 15% of placebo recipients compared with 7% of combined oseltamivir recipients (P = .03). Among all 629 subjects, oseltamivir reduced illness duration (76.3 hours and 74.3 hours for 75 mg and 150 mg, respectively, vs 97.0 hours for placebo; P = .004 for both comparisons) and illness severity (686 score-hours and 629 score-hours for 75 mg and 150 mg, respectively, vs 887 score-hours for placebo; P < .001 for both comparisons). Nausea and vomiting occurred more frequently in both oseltamivir groups (combined, 18.0% and 14.1%, respectively; P = .002) than in the placebo group (7.4% and 3.4%; P < .001).Our data suggest that oral oseltamivir treatment reduces the duration and severity of acute influenza in healthy adults and may decrease the incidence of secondary complications.
Home-made vacuum syringe for endoscopic ultrasound-guided fine-needle aspiration
Authors: A. Grillo, P. Fusaroli, A. Naik, E. Giovannini, G. Gasbarrini, G. Caletti
Journal: Endoscopy (2006)

Fine-needle aspiration (FNA) has become an integral part of endoscopic ultrasound (EUS) procedures. EUS-FNA is performed using two types of needles: (a) single-use needles, with only one vacuum-lock aspiration syringe supplied (made by Wilson-Cook, Medi-Globe, and Olympus); and (b) needles with a reusable handle, with no syringe supplied (Olympus NA-10J-1 or NA-11J-KB; Olympus, Hamburg, Germany, Europe).
EFFECT OF IVABRADINE IN COMBINATION WITH BETA-BLOCKERS VERSUS BETA-BLOCKERS UPTITRATION ON LEFT VENTRICULAR FUNCTIONS IN PATIENTS WITH ACUTE ANTERIOR MYOCARDIAL INFARCTION AND EARLY SYSTOLIC DYSFUNCTION
Authors: Kateryna Amosova, Yao Xu, Igor Prudkiy, luliia Rudenko, Andrii Bezrodnyi, Yuriy Sychenko
Journal: Journal of the American College of Cardiology (2012)
A Cluster of Acinetobacter Pneumonia in Foundry Workers
Authors: LESTER G. CORDES
Journal: Annals of Internal Medicine (1981)

In a 3-month period, three men who had worked for 5 to 19 years as welders or grinders of steel castings in a foundry acquired pneumonia caused by Acinetobacter calcoaceticus variety anitratus serotype 7J. Two of the men died, and postmortem examination showed mixed-dust pneumoconiosis with iron particles in the lungs. A. calcoaceticus variety anitratus serotype 7J was isolated from the air in the foundry but the source was not found. The prevalence of antibody titers of 64 or greater to the 7J strain was significantly higher among foundry workers (15%) than among community controls (2%) (p < 0.01). Sampling showed that the concentrations of total and metallic particles (especially iron) and of free silica in air inhaled by welders and grinders at the foundry frequently exceeded acceptable levels. These findings suggest that chronic exposure to such particles may increase susceptibility to infection by this organism, which rarely affects healthy people.
Elevated MMP-12 protein levels in induced sputum from patients with COPD
Authors: I K Demedts
Journal: Thorax (2005)

<b>Background:</b> Several matrix metalloproteinases (MMPs) are involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). In mice, MMP-12 plays a crucial role in the development of cigarette smoke induced emphysema. A study was undertaken to investigate the role of MMP-12 in the development of COPD in human smokers. <b>Methods:</b> Induced sputum samples were collected from patients with stable COPD (n = 28), healthy smokers (n = 14), never smokers (n = 20), and former smokers (n = 14). MMP-12 protein levels in induced sputum were determined by ELISA and compared between the four study groups. MMP-12 enzymatic activity in induced sputum was evaluated by casein zymography and by cleaving of a fluorescence quenched substrate. <b>Results:</b> Median (IQR) MMP-12 levels were significantly higher in COPD patients than in healthy smokers, never smokers, and former smokers (17.5 (7.1–42.1) <i>v</i> 6.7 (3.9–10.4) <i>v</i> 4.2 (2.4–11.3) <i>v</i> 6.1 (4.5–7.6) ng/ml, p = 0.0002). MMP-12 enzymatic activity was significantly higher in patients with COPD than in controls (4.11 (1.4–8.0) <i>v</i> 0.14 (0.1–0.2) μg/μl, p = 0.0002). <b>Conclusion:</b> MMP-12 is markedly increased in induced sputum from patients with stable COPD compared with controls, suggesting a role for MMP-12 in the development of COPD in smokers.
Acute Stress Disorder as a Predictor of Posttraumatic Stress Symptoms
Authors: Catherine Classen, Cheryl Koopman, Robert Hales, David Spiegel
Journal: American Journal of Psychiatry (1998)

Using the DSM-IV diagnostic criteria for acute stress disorder, the authors examined whether the acute psychological effects of being a bystander to violence involving mass shootings in an office building predicted later posttraumatic stress symptoms.The participants in this study were 36 employees working in an office building where a gunman shot 14 persons (eight fatally). The acute stress symptoms were assessed within 8 days of the event, and posttraumatic stress symptoms of 32 employees were assessed 7 to 10 months later.According to the Stanford Acute Stress Reaction Questionnaire, 12 (33%) of the employees met criteria for the diagnosis of acute stress disorder. Acute stress symptoms were found to be an excellent predictor of the subjects' posttraumatic stress symptoms 7-10 months after the traumatic event.These results suggest not only that being a bystander to violence is highly stressful in the short run, but that acute stress reactions to such an event further predict later posttraumatic stress symptoms.
Purification of cachectin, a lipoprotein lipase-suppressing hormone secreted by endotoxin-induced RAW 264.7 cells.
Authors: B Beutler, J Mahoney, N Le Trang, P Pekala, A Cerami
Journal: The Journal of Experimental Medicine (1985)

Previous studies have indicated that endotoxin and other bacterial and protozoal products can stimulate macrophages to produce a factor that can suppress the activity of the enzyme lipoprotein lipase (LPL), in vivo and in vitro. In the present report we describe the purification of this factor, cachectin, to apparent homogeneity from the conditioned medium of endotoxin-stimulated RAW 264.7 cells. The isolated protein has an isoelectric point of 4.7 and a subunit molecular weight of 17,000. Although cachectin's isoelectric point and molecular weight are similar to those described for interleukin 1, pure cachectin has no leukocyte-activating factor (LAF) activity. Cachectin at a concentration of 10(-11) M has the ability to suppress the LPL activity of the 3T3-L1 adipocyte cell line by 80%. Binding studies using radio-labeled cachectin and 3T3-L1 adipocytes and C2 myotubules revealed approximately 10(4) high-affinity receptors per cell on both cell types (Ka, 3 X 10(9]. Cachectin receptors were also present on liver membranes but were absent on erythrocytes and lymphocytes. The isolation of cachectin and characterization of its receptor should facilitate further investigations into the role of cachectin and other macrophage mediators in the metabolic derangements that occur during infection and cachexia.
Newly awakened interest in sleep research spans many specialties
Authors: Lynne Lamberg
Journal: JAMA (1985)

The diversity of specialists attending recent meetings where sleep research results were presented— chest physicians, neurologists, psychiatrists, pediatricians, internists, otolaryngologists, cardiologists, physiologists, and others—reflects the scope of the newly-awakened interest in this relatively young area of medical science (<i>JAMA</i>[MEDICAL NEWS] 1985; 254:1125-1133). Sessions on sleep-disordered breathing, cosponsored for the first time by the Association of Sleep Disorders Centers and the American College of Chest Physicians (during the latter's 50th annual scientific assembly) drew standingroom only crowds. They heard Martin A. Cohn, MD, suggest that "some 40% to 50% of the population over age 50 [years] may experience sleep-disordered breathing." Cohn, who is director, Sleep Disorders Center, Mt Sinai Medical Center, and assistant professor of medicine, University of Miami (Fla) School of Medicine, says that, "although the spectrum of severity of these disorders is quite wide, about 5% of the general adult population and 10% of men over
The effects of acid precipitation runoff episodes on reservoir and tapwater quality in an Appalachian Mountain water supply.
Authors: W E Sharpe, D R DeWalle
Journal: Environmental Health Perspectives (1990)

The aluminum concentration and Ryznar Index increased and the pH decreased in a small Appalachian water supply reservoir following acid precipitation runoff episodes. Concomitant increases in tapwater aluminum and decreases in tapwater pH were also observed at two homes in the water distribution system. Lead concentrations in the tapwater of one home frequently exceeded recommended levels, although spatial and temporal variation in tapwater copper and lead concentrations was considerable. Since source water and reservoir water copper and lead concentrations were much lower, the increased copper and lead concentrations in tapwater were attributed to corrosion of household plumbing. Tapwater copper concentration correlated well with tapwater pH and tapwater temperature. Asbestos fibers were not detected in tapwater. The asbestos-cement pipe in the water distribution system was protected by a spontaneous metallic coating that inhibited fiber release from the pipe. Several simultaneous reactions were hypothesized to be taking place in the distribution system that involved corrosion of metallic components and coating of asbestos-cement pipe components in part with corrosion products and in part by cations of watershed origin. Greater water quality changes might be expected in areas of higher atmospheric deposition.
The Anatomy of First-Episode and Chronic Schizophrenia: An Anatomical Likelihood Estimation Meta-Analysis
Authors: Ian Ellison-Wright, David C. Glahn, Angela R. Laird, Sarah M. Thelen, Ed Bullmore
Journal: American Journal of Psychiatry (2008)

Objective: The authors sought to map gray matter changes in first-episode schizophrenia and to compare these with the changes in chronic schizophrenia. They postulated that the data would show a progression of changes from hippocampal deficits in first-episode schizophrenia to include volume reductions in the amygdala and cortical gray matter in chronic schizophrenia. Method: A systematic search was conducted for voxel-based structural MRI studies of patients with first-episode schizophrenia and chronic schizophrenia in relation to comparison groups. Meta-analyses of the coordinates of gray matter differences were carried out using anatomical likelihood estimation. Maps of gray matter changes were constructed, and subtraction meta-analysis was used to compare them. Results: A total of 27 articles were identified for inclusion in the meta-analyses. A marked correspondence was observed in regions affected by both first-episode schizophrenia and chronic schizophrenia, including gray matter decreases in the thalamus, the left uncus/amygdala region, the insula bilaterally, and the anterior cingulate. In the comparison of first-episode schizophrenia and chronic schizophrenia, decreases in gray matter volume were detected in first-episode schizophrenia but not in chronic schizophrenia in the caudate head bilaterally; decreases were more widespread in cortical regions in chronic schizophrenia. Conclusions: Anatomical changes in first-episode schizophrenia broadly coincide with a basal ganglia-thalamocortical circuit. These changes include bilateral reductions in caudate head gray matter, which are absent in chronic schizophrenia. Comparing first-episode schizophrenia and chronic schizophrenia, the authors did not find evidence for the temporolimbic progression of pathology from hippocampus to amygdala, but there was evidence for progression of cortical changes.
Adenotonsillectomy as First-Line Treatment for Sleep-disordered Breathing in Obese Children
Authors: Stijn L. Verhulst, Jan De Backer, Luc Van Gaal, Wilfried De Backer, Kristine Desager
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

We read with great interest the article by Dr. Amin and colleagues, who assessed risk factors for recurrence of sleepdisordered breathing in children 1 year after adenotonsillectomy (1). The authors demonstrated that there was a high risk of recurrence—that is, 79% of the obese children studied still had sleep-disordered breathing 1 year after surgery. Postoperative gain in body mass index (BMI), obesity, and being African American increased the risk of reappearance of sleep apnea. In their conclusion, the authors advocate long-term follow-up of children with sleep-disordered breathing, monitoring of BMI gain, and reevaluation of children who demonstrate rapid BMI gain. We would like to add two other important implications for clinical practice and for future research, specific for obese children. It has already been documented that overweight children with sleep apnea gain weight after upper airway surgery (2), which is possibly mediated by a decrease in sleep and waking motor activity (3). In view of the finding by Amin and coworkers that accelerated weight gain is a significant risk factor for recurrence of apnea, we would like to recommend that weight loss strategies be implemented prior to upper airway surgery in obese children. Possibly, weight loss therapy could also be considered as a first-line treatment for obstructive sleep apnea syndrome in obese children. However, to date there are no systematic studies investigating the effects of spontaneous weight loss on the severity of sleep-disordered breathing in childhood obesity (2). It is clear that more research on this topic is urgently needed. Second, this study confirmed that adenotonsillectomy is only successful in a subset of the obese population with obstructive sleep apnea (2). Since obesity can be considered as a risk factor for postoperative complications, it is worthwhile to develop imaging techniques which could preoperatively assess airway anatomy and functional characteristics to identify patients who are likely to benefit from surgical intervention. One of these possible techniques is computational fluid dynamics, which is now being increasingly used in the field of sleep-disordered breathing both in children (4) and adults (5). In conclusion, we would like to recommend more research on the influence of weight management and on patient selection criteria for adenotonsillectomy in obese children with obstructive sleep apnea syndrome.
14 ALL-ORAL SOFOSBUVIR-BASED 12-WEEK REGIMENS FOR THE TREATMENT OF CHRONIC HCV INFECTION: THE ELECTRON STUDY
Authors: E.J. Gane, C.A. Stedman, R.H. Hyland, P.S. Pang, X. Ding, W.T. Symonds, J.G. McHutchison
Journal: Journal of Hepatology (2013)
Principles of Human Genetics
Authors: James C. King
Journal: JAMA (1973)

The 1949 edition of this book was the first American text on the subject written by a geneticist of the post-eugenics school. An experimental geneticist himself, Stern brought together material illustrating the ways in which the concepts of the fast-growing science could be applied to human data. His book was sober, accurate, and analytical—neither a museum of congenital monstrosities nor a harangue for sterilization of the unfit. It had a great influence toward the development of a sound science of human genetics. It was followed in 1960 by a larger, updated, second edition in the same tradition. We now have a still larger third. All three editions of Stern's book have aimed at an encyclopedic rather than an introductory coverage of the subject. This aim was substantially achieved in the first two editions, but the third no longer has the former comprehensiveness. The years since 1960 have seen genetics revolutionized
Patients' expectations in relation to outcome of total hip replacment surgery.
Authors: K E Burton, V Wright, J Richards
Journal: Annals of the Rheumatic Diseases (1979)

The importance of expectations has been assessed by giving 88 patients who had undergone total hip replacement surgery a series of visual analogue scales to provide a pain score, a 5-point rating scale to assess their remembered expectations, and an interview to establish clinical, functional, social, and psychological data. Patients generally had high expectations, but only 55% had their expectations fulfilled. Despite this, 86% claimed the operation to be successful, though when questioned more closely patients noted a certain amount of displeasure about the outcome. Further analysis revealed that, when the sample was split into 2 groups of fulfilled and unfulfilled expectations, significant differences were noted in that the quality of life enjoyed by the former group was greater than that enjoyed by the latter group. This finding suggests that the notion of 'success' is not as effective as the notion of 'expectations' as a measure of the outcome of total hip replacement surgery.
The Late Sir Farquhar Buzzard
Authors: A. M. Cooke
Journal: BMJ (1972)

isotopes could ethically be given.All three patients were able to form 25-hydroxycholecalciferol to the same extent as non- Pakistani control patients with a similar de- gree of vitamin D deficiency.The two Pakistani patients were also shown to form the potent biologically active metabolite 1,25 dihydroxycholecalciferol.Details relating to one of these patients have been published.2We feel therefore that inability to produce the appropriate metabolites of vitamin D is not the explanation for the phenomena re- ported in both surveys.-We are, etc.,