tbuckley/cabot-search huggingface dataset:
Stratification of risk for hospital admissions for injury related to fall: cohort study
Authors: V. M. Castro, T. H. McCoy, A. Cagan, H. R. Rosenfield, S. N. Murphy, S. E. Churchill, I. S. Kohane, R. H. Perlis
Journal: BMJ (2014)

<b>Objective</b> To determine whether the ability to stratify an individual patient's hazard for falling could facilitate development of focused interventions aimed at reducing these adverse outcomes. <b>Design</b> Clinical and sociodemographic data from electronic health records were utilized to derive multiple logistic regression models of hospital readmissions for injuries related to falls. Drugs used at admission were summarized based on reported adverse effect frequencies in published drug labeling. <b>Setting</b> Two large academic medical centers in New England, United States. <b>Participants</b> The model was developed with 25 924 individuals age ≥40 with an initial hospital discharge. The resulting model was then tested in an independent set of 13 032 inpatients drawn from the same hospital and 36 588 individuals discharged from a second large hospital during the same period. <b>Main outcome measure</b> Hospital readmissions for injury related to falls. <b>Results</b> Among 25 924 discharged individuals, 680 (2.6%) were evaluated in the emergency department or admitted to hospital for a fall within 30 days of discharge, 1635 (6.3%) within 180 days of discharge, 2360 (9.1%) within one year, and 3465 (13.4%) within two years. Older age, female sex, white or African-American race, public insurance, greater number of drugs taken on discharge, and score for burden of adverse effects were each independently associated with hazard for fall. For drug burden, presence of a drug with a frequency of adverse effects related to fall of 10% was associated with 3.5% increase in odds of falling over the next two years (odds ratio 1.04, 95% confidence interval 1.02 to 1.05). In an independent testing set, the area under the receiver operating characteristics curve was 0.65 for a fall within two years based on cross sectional data and 0.72 with the addition of prior utilization data including age adjusted Charlson comorbidity index. Portability was promising, with area under the curve of 0.71 for the longitudinal model in a second hospital system. <b>Conclusions</b> It is potentially useful to stratify risk of falls based on clinical features available as artifacts of routine clinical care. A web based tool can be used to calculate and visualize risk associated with drug treatment to facilitate further investigation and application.
Daily oral verapamil before but not after rapid atrial excitation prevents electrical remodeling
Authors: Y Kurita
Journal: Cardiovascular Research (2002)

Intravenous verapamil has been reported to prevent electrical remodeling induced by rapid atrial excitation of several minutes to several hours. However, the clinical efficacy of verapamil when taken orally and daily remains controversial.We attempted to demonstrate our hypothesis that if verapamil prevents calcium (Ca) overload, its efficacy would be greater when taken before, rather than after, the onset of rapid atrial excitation.In 24 dogs, pacing and recording electrodes were sutured onto the right atrium. After a 5-day recovery period, rapid atrial pacing at 400 ppm was started, followed 2 days later by oral verapamil (8 mg/kg per day) in eight dogs (After group; A). In another eight dogs, oral verapamil administration was begun 1 week before the initiation of rapid pacing (Before group; B). In the remaining eight dogs, only rapid atrial pacing was started, without oral verapamil (Control group; C). We measured the effective refractory period (ERP) and conduction velocity (CV), and calculated wavelength (WL) at cycle lengths 200 and 300 ms on the day before (P0), and after 2 (P2), 7 (P7), 14(P14) days of rapid pacing.In response to rapid atrial pacing, ERP, CV, WL decreased and progressively and comparably in A and C (P<0.05 vs. P0). In contrast, in B, these parameters did not change significantly and remained greater than those in A and C (P<0.05). Moreover, the adaptation of ERP to rate was preserved only in B. The duration of atrial fibrillation (AF) was shorter in B than in A and C (P<0.05). The inducibility of AF tended to be lower, and the fibrillation cycle length was longer in B than in A and C.Oral verapamil started before but not after rapid atrial excitation prevents electrical remodeling. Verapamil may exert beneficial effects when it is taken during sinus rhythm, but not after more than 2 days of atrial tachyarrhythmia.
Randomised trial of endoscopic balloon dilation versus endoscopic sphincterotomy for removal of bileduct stones
Authors: Jacques JGHM Bergman, Erik AJ Rauws, Paul Fockens, Anne-Marie van Berkel, Patrick MM Bossuyt, Jan GP Tijssen, Guido NJ Tytgat, Kees Huibregtse
Journal: The Lancet (1997)
Dissecting human T cell responses against Bordetella species.
Authors: M T De Magistris, M Romano, S Nuti, R Rappuoli, A Tagliabue
Journal: The Journal of Experimental Medicine (1988)

To identify the minimal structures that may be important for the creation of a synthetic and/or recombinant vaccine against whooping cough, human T cell clones were obtained against Bordetella antigens. Cloned peripheral blood T lymphocytes from an immune donor were grown in IL-2 and tested for proliferation in response to inactivated Bordetella species (B. pertussis, B. parapertussis, and B. bronchiseptica) and mutants deficient for the expression of virulence-associated antigens. All the T cell clones obtained were CD4+8- and recognized specifically the Bordetella antigens when presented by autologous B cells. On the basis of the responsiveness to the whole inactivated bacteria, it was possible to cluster the 12 clones obtained into four groups with the following specificity: (1) filamentous hemagglutinin (FHA); (2) B. pertussis-specific antigens; (3) virulence-associated Bordetella-specific antigens; and (4) nonvirulence-associated Bordetella-specific antigens. Using two new B. pertussis deletion mutants, clone 6 (representative of cluster 1) was found to recognize the COOH terminus of FHA. Furthermore, three out of four clones of cluster 3 were specifically stimulated by the soluble 69-kD protein from the outer membrane of B. pertussis. Surprisingly, none of the twelve clones obtained by stimulation in vitro with whole inactivated bacteria recognized pertussis toxin (PT), which is believed to be the most important protein to be included in an acellular vaccine. However, when a new generation of clones was obtained using soluble PT as the in vitro stimulus, it was observed that 11 clones of this group recognized this antigen. Thus, PT does not seem to be the most representative antigen on the whole inactivated bacteria, although T cell memory against PT exists in a donor who had the disease several years ago.
The Role for Endoplasmic Reticulum Stress in Diabetes Mellitus
Authors: Décio L. Eizirik, Alessandra K. Cardozo, Miriam Cnop
Journal: Endocrine Reviews (2007)

Accumulating evidence suggests that endoplasmic reticulum (ER) stress plays a role in the pathogenesis of diabetes, contributing to pancreatic β-cell loss and insulin resistance. Components of the unfolded protein response (UPR) play a dual role in β-cells, acting as beneficial regulators under physiological conditions or as triggers of β-cell dysfunction and apoptosis under situations of chronic stress. Novel findings suggest that “what makes a β-cell a β-cell”, i.e., its enormous capacity to synthesize and secrete insulin, is also its Achilles heel, rendering it vulnerable to chronic high glucose and fatty acid exposure, agents that contribute to β-cell failure in type 2 diabetes. In this review, we address the transition from physiology to pathology, namely how and why the physiological UPR evolves to a proapoptotic ER stress response and which defenses are triggered by β-cells against these challenges. ER stress may also link obesity and insulin resistance in type 2 diabetes. High fat feeding and obesity induce ER stress in liver, which suppresses insulin signaling via c-Jun N-terminal kinase activation. In vitro data suggest that ER stress may also contribute to cytokine-induced β-cell death. Thus, the cytokines IL-1β and interferon-γ, putative mediators of β-cell loss in type 1 diabetes, induce severe ER stress through, respectively, NO-mediated depletion of ER calcium and inhibition of ER chaperones, thus hampering β-cell defenses and amplifying the proapoptotic pathways. A better understanding of the pathways regulating ER stress in β-cells may be instrumental for the design of novel therapies to prevent β-cell loss in diabetes.
AN EFFICIENT INTESTINAL ANTISEPTIC: The Perchlorides of Mercury and Iron in Combination
Authors: T. S. Wilson
Journal: BMJ (1924)

JOU syplhilis of the central nervous system so far as we have beenl able to ascertain.5. Definite changes (other than a complete positive, and in the absence of blood) indicate apparently some definite pathological change in the cerebro-spinal fluid; but all pathological fluids do not necessarily show any colloidal beiizoin reaction.
THE CONTROL OF DIPHTHERIA AND SCARLET FEVER
Authors: R. A. O'Brien
Journal: BMJ (1928)

stationary after post-operative improve,ment, radliotherapy is useless.They end up witlh a warning agailnst exagger- ating the definite cuirative value of radiotherapy, anid call upon the pathologists to adopt a universal' terminiology for the different types of tumouls, and at the same time to group therm accordinig to their radio-sensibility or their radio-resistance.
Carcinoembryonic antigen (CEA) in the normal human small intestine: a light and electron microscopic study.
Authors: P Isaacson, M A Judd
Journal: Gut (1977)

An immunoperoxidase method for the demonstration of carcinoembryonic antigen (CEA) in tissues was applied to formalin-fixed paraffin embedded and glutaraldehyde-fixed resin sections of normal human small intestine. CEA could easily be demonstrated coating the surface of the small intestine, lining the crypts, and in goblet cells, indicating its presence there in considerable concentration. At the ultrastructural level CEA was localised in the glycocalyx and in mucin granules of goblet cells but not intracytoplasmically.
Use of Cytotoxic Agents and Cyclosporine in the Treatment of Autoimmune Disease: Part 2: Inflammatory Bowel Disease, Systemic Vasculitis, and Therapeutic Toxicity
Authors: Carol A. Langford
Journal: Annals of Internal Medicine (1998)

When cytotoxic agents were introduced, their ability to disrupt nucleic acid and protein synthesis led to their effective use for the treatment of neoplastic disease.During the course of this use, however, it became apparent that these agents also suppress the immune system. This usually unwelcome effect was subsequently studied and beneficially directed toward the treatment of non-neoplastic diseases in which autoimmune mechanisms were considered important to pathogenesis. As a result of these investigations, cytotoxic agents and, more recently, cyclosporine have emerged to become an important part of the therapeutic regimen for many autoimmune diseases. Nonetheless, these medications may still cause treatment-induced illness or even death. It is therefore particularly important to weigh the benefits and risks of cytotoxic therapy when treating a non-neoplastic disease. This two-part Clinical Staff Conference reviews data on the efficacy and toxicity of cytotoxic drugs and cyclosporine in selected autoimmune diseases. In part 2, we focus on the role of these agents in treating inflammatory bowel disease and systemic vasculitis and review the toxic effects of these agents.
Differences in gene copy number carried by different MHC ancestral haplotypes. Quantitation after physical separation of haplotypes by pulsed field gel electrophoresis.
Authors: W J Zhang, M A Degli-Esposti, T J Cobain, P U Cameron, F T Christiansen, R L Dawkins
Journal: The Journal of Experimental Medicine (1990)

We have examined the hypothesis that MHC ancestral haplotypes have a specific content of genes regulating the extent of autoimmune reactions. Gene copy number was quantitated by objective densitometry after PFGE was used to separate heterozygous AHs of different lengths. Initially we analyzed examples of known gene copy number at the C4 and 21 hydroxylase loci and showed that the approach provides predictable results. We then studied heterozygotes containing one characterized and one uncharacterized AH with particular attention to the gene copy number at the C4, Cyp21, and DRB loci. Each AH studied has a characteristic gene copy number at each locus studied. The same may be true of TNF, but other possibilities must be considered. AHs are markers for extensive chromosomal segments including particular numbers of several functional genes. Since AHs mark susceptibility to autoimmune disease, differences in gene copy number may be implicated.
Extended Valganciclovir Prophylaxis to Prevent Cytomegalovirus After Lung Transplantation
Authors: Scott M. Palmer, Ajit P. Limaye, Missy Banks, Dianne Gallup, Jeffrey Chapman, E. Clinton Lawrence, Jordan Dunitz, Aaron Milstone, John Reynolds, Gordon L. Yung, Kevin M. Chan, Robert Aris, Edward Garrity, Vincent Valentine, Jonathan McCall, Shein Chung Chow, Robert Duane Davis, Robin Avery
Journal: Annals of Internal Medicine (2010)

Background: Cytomegalovirus (CMV) is the most prevalent opportunistic infection after lung transplantation. Current strategies do not prevent CMV in most at-risk patients. Objective: To determine whether extending prophylaxis with oral valganciclovir from the standard 3 months to 12 months after lung transplantation is efficacious. Design: Randomized, clinical trial. Patients were randomly assigned by a central automated system to treatment or placebo. Patients and investigators were blinded to treatment status. (ClinicalTrials.gov registration number: NCT00227370) Setting: Multicenter trial involving 11 U.S. lung transplant centers. Patients: 136 lung transplant recipients who completed 3 months of valganciclovir prophylaxis. Intervention: 9 additional months of oral valganciclovir (n = 70) or placebo (n = 66). Measurements: The primary end point was freedom from CMV disease (syndrome or tissue-invasive) on an intention-to-treat basis 300 days after randomization. Secondary end points were CMV disease severity, CMV infection, acute rejection, opportunistic infections, ganciclovir resistance, and safety. Results: CMV disease occurred in 32% of the short-course group versus 4% of the extended-course group (P < 0.001). Significant reductions were observed with CMV infection (64% vs. 10%; P < 0.001) and disease severity (110 000 vs. 3200 copies/mL, P = 0.009) with extended treatment. Rates of acute rejection, opportunistic infections, adverse events, CMV UL97 ganciclovir-resistance mutations, and laboratory abnormalities were similar between groups. During the 6 months after study completion, a low incidence of CMV disease was observed in both groups. Limitation: Longer-term effects of extended prophylaxis were not assessed. Conclusion: In adult lung transplant recipients who have received 3 months of valganciclovir, extending prophylaxis by an additional 9 months significantly reduces CMV infection, disease, and disease severity without increased ganciclovir resistance or toxicity. A beneficial effect with regard to prevention of CMV disease seems to extend at least through 18 months after transplantation. Primary Funding Source: Roche Pharmaceuticals.
Efficient In Vivo Delivery of siRNA to the Liver by Conjugation of α-Tocopherol
Authors: Kazutaka Nishina, Toshinori Unno, Yoshitaka Uno, Takayuki Kubodera, Tadashi Kanouchi, Hidehiro Mizusawa, Takanori Yokota
Journal: Molecular Therapy (2008)

RNA interference is a powerful tool for target-specific knockdown of gene expression. However, efficient and safe in vivo delivery of short interfering RNA (siRNA) to the target organ, which is essential for therapeutic applications, has not been established. In this study we used α-tocopherol (vitamin E), which has its own physiological transport pathway to most of the organs, as a carrier molecule of siRNA in vivo. The α-tocopherol was covalently bound to the antisense strand of 27/29-mer siRNA at the 5'-end (Toc-siRNA). The 27/29-mer Toc-siRNA was designed to be cleaved by Dicer, producing a mature form of 21/21-mer siRNA after releasing α-tocopherol. The C6 hydroxyl group of α-tocopherol, associated with antioxidant activity, was abolished. Using this new vector, intravenous injection of 2 mg/kg of Toc-siRNA, targeting apolipoprotein B (apoB), achieved efficient reduction of endogenous apoB messenger RNA (mRNA) in the liver. The downregulation of apoB mRNA was confirmed by the accumulation of lipid droplets in the liver as a phenotype. Neither induction of interferons (IFNs) nor other overt side effects were revealed by biochemical and pathological analyses. These findings indicate that Toc-siRNA is effective and safe for RNA interference-mediated gene silencing in vivo.
Zebrafish as a “Biosensor”? Effects of Ionizing Radiation and Amifostine on Embryonic Viability and Development
Authors: Geoffrey A. Geiger, Sharon E. Parker, Andrew P. Beothy, Jennifer A. Tucker, Mary C. Mullins, Gary D. Kao
Journal: Cancer Research (2006)

Abstract The zebrafish (Danio rerio) has emerged as a popular vertebrate model system for cancer and treatment-related research. Benefits include ease of care, rapid development, optical clarity of embryos, which allows visualization of major organ systems, and opportunities for genetic manipulation. However, specific parameters of radiation sensitivity have not been systematically documented. We investigated the effects of radiation and a radiomodifier on zebrafish viability and embryonic development. Embryos were exposed to γ-radiation (5, 10, or 20 Gy) at sequential times postfertilization and serially assessed for viability and morphologic abnormalities. As expected, lethality and morphologic perturbations were more pronounced earlier in embryogenesis and with higher radiation doses and were partially reversed by amifostine. The effects of radiation and concurrent treatment with amifostine on the developmental organization of the eye and brain were striking. Radiation resulted in hypocellularity and disorganization of the cellular layers of the retina, effects partially reversed by amifostine, as well as lens opacification. Radiation strikingly reduced the volume of brain, but the volume loss was substantially blocked by amifostine. Increased terminal deoxyribonucleotidyl transferase–mediated dUTP nick end labeling signal was noted in both the irradiated eye and brain, but reduced by amifostine. Finally, irradiating embryos resulted in caspase activation detectable in 96-well microplates, which was proportional to the number of embryos and radiation dose; the degree of activation was markedly reduced by amifostine. These results together suggest the power and versatility of the zebrafish in assessing the effects of radiation and radiomodifiers on organ and tissue development. (Cancer Res 2006; 66(16): 8172-81)
Bronchoalveolar Lavage Cellularity
Authors: ATHOL U. WELLS, DAVID M. HANSELL, PATRICIA L. HASLAM, MICHAEL B. RUBENS, JEREMY CAILES, CAROL M. BLACK, ROLAND M. du BOIS
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Lone cryptogenic fibrosing alveolitis (CFA) is histologically identical to fibrosing alveolitis associated with systemic sclerosis (FASSc), but it has a much worse prognosis after matching for disease severity at presentation. The aims of this study were to gain insights into possible pathogenetic mechanisms contributing to this prognostic difference, by comparing bronchoalveolar lavage (BAL) cellularity in the two diseases, and to evaluate the relationships between BAL findings and the regional and global extent of disease, quantified by thin-section computed tomography (CT) and lung function indices. Patients with CFA were distinguished by more extensive fibrosing alveolitis on CT (p < 0.02) and by higher counts of neutrophils (total per ml, p < 0.02; percentage p < 0.03) and eosinophils (total per ml, p < 0.002; percentages, p < 0.02) in BAL fluid. After adjustment for functional and morphologic measures of disease extent, eosinophil percentages and total counts were increased in CFA (p < 0.05 in all 12 multivariate models), but they were not independently related to regional or global disease severity. Neutrophil percentages and total counts were virtually identical in CFA and FASSc in disease of comparable severity, and they increased with increasingly extensive lobar disease and global disease, as judged by CT, p < 0.0005 in all analyses. Neutrophil levels were more closely linked to the extent of disease on CT than to the severity of functional impairment, on univariate and multivariate analysis. The higher BAL eosinophil levels seen in CFA, compared with those seen in FASSc, after adjustment for disease extent, indicate that an eosinophilic influx may be linked to the pathogenesis of fibrosing alveolitis. By contrast, BAL neutrophil levels increase with increasingly extensive disease on CT, but they do not differ independently between CFA and FASSc, suggesting that neutrophil degradation products are unlikely to account for the excess mortality in CFA, compared with that in FASSc.
LAWYERS' USE OF PSYCHIATRY
Authors: MELVIN L. SELZER, ELISSA P. BENEDEK
Journal: American Journal of Psychiatry (1965)

A poll of 60 attorneys revealed that they used psychiatric consultation sparingly. Deterrents cited were expense to clients, clients' resentment at being sent to a psychiatrist, and psychiatrists' unavailability as well as lack of interest in legal matters. Most requests for psychiatric consultation were related to domestic problems, with criminal cases a distant second. Although many attorneys realize clients need psychiatric help, referrals are rarely made for purposes of treatment. Our impression is that lawyers use psychiatrists to help "the case" rather than the client.
Ethics and the Moment of Clinical Truth
Authors: Edmund D. Pellegrino
Journal: JAMA (1978)

That medicine is, in large part, a moral enterprise has been evident since physicians and philosophers began critically to reflect on its nature and purposes. Ethics has, since the Hippocratics and the Attic philosophers, been taught in some form to future physicians. What seems remarkable about the current renaissance in medical ethics is that for the first time it is being realized that it can be taught as a formal intellectual discipline integral to clinical medicine. Ethics, like any primary discipline that supports the physician's endeavours, can survive only if it is explicitly linked to the physician's central enterprise. That enterprise is the act of clinical decision—the choice among the many things that<i>can</i>be done and those that<i>ought</i>to be done for a given patient in a given clinical circumstance. This is the physician's essential act—that which makes medicine more than a summation of primary disciplines in the