tbuckley/cabot-search huggingface dataset:
Effect of Mass Distribution of Azithromycin for Trachoma Control on Overall Mortality in Ethiopian Children
Authors: Travis C. Porco, Teshome Gebre, Berhan Ayele, Jenafir House, Jeremy Keenan, Zhaoxia Zhou, Kevin Cyrus Hong, Nicole Stoller, Kathryn J. Ray, Paul Emerson, Bruce D. Gaynor, Thomas M. Lietman
Journal: JAMA (2009)

<h3>Context</h3>Mass oral azithromycin distribution to affected communities is a cornerstone of the World Health Organization's trachoma elimination program. Antibiotics are provided to target the ocular strains of chlamydia that cause trachoma, but may also be efficacious against respiratory disease, diarrhea, and malaria—frequent causes of childhood mortality in trachoma-endemic areas.<h3>Objective</h3>To compare mortality rates of participants aged 1 to 9 years in treated communities with those in untreated communities.<h3>Design, Setting, and Participants</h3>We conducted a cluster-randomized clinical trial of mass azithromycin administration for trachoma control. Forty-eight communities (known as subkebeles) were randomized into 1 of 3 treatment schedules (annual treatment of all residents [15 902 participants], biannual treatment of all residents [17 288 participants], or quarterly treatment of children only [14 716 participants]) or into 1 group for which treatment was delayed by 1 year (control, 18 498 participants). Twelve subkebeles were randomized to each of the 4 schedules with all children in each of the 3 communities being eligible for treatment. The trial was conducted in a field setting in rural Ethiopia, May 2006 to May 2007.<h3>Interventions</h3>A single dose of oral azithromycin (adults, 1 g; children, 20 mg/kg) was administered for treatment of ocular Chlamydia trachomatis infection. Antibiotic coverage levels for children aged 1 to 9 years exceeded 80% at all visits.<h3>Main Outcome Measure</h3>The main outcome measure was the community-specific mortality risk for children aged 1 to 9 years over the course of 1 year. Mortality was measured by enumerative census at baseline and again after 1 year. Comparison of the risk of mortality was a prespecified outcome for the clinical trial.<h3>Results</h3>The odds ratio for childhood mortality in the intervention communities was 0.51 (95% confidence interval, 0.29-0.90; P = .02; clustered logistic regression) compared with the control group. In the treated communities, the estimated overall mortality rate during this period for children aged 1 to 9 years in the untreated group was 8.3 per 1000 person-years (95% confidence interval, 5.3-13.1), while among the treated communities, the estimated overall mortality rate was 4.1 per 1000 person-years (95% confidence interval, 3.0-5.7) for children aged 1 to 9 years.<h3>Conclusion</h3>In a trachoma-endemic area, mass distribution of oral azithromycin was associated with reduced mortality in children.<h3>Trial Registration</h3>clinicaltrials.gov Identifier: NCT00322972
Abstract 484: A role for mDia formins in epithelial ovarian cancer spheroid invasion
Authors: Krista Pettee, Kathryn M. Eisenmann
Journal: Cancer Research (2012)

Abstract Ovarian Cancers (OvCa) metastasis is highly unusual, relative to other metastatic cancers, and is typically confined to the peritoneal cavity; metastases are derived from exfoliated epithelial ovarian cancer (EOC) cells that adhere to and invade the mesothelial cell layer and extracellular matrix (ECM) underlying the peritoneal cavity and viscera. Exfoliated ovarian tumor cells are detected in the peritoneal ascites as single cells, small aggregates or highly ordered, compacted multi-cellular spheroids Compacted spheroids are poorly understood yet clinically relevant structures that are highly invasive and chemoresistant. Little is known about the molecular underpinnings of EOC spheroid formation or their cellular invasion into the underlying peritoneal mesothelial lining. Spheroid formation and ensuing invasion requires tight regulation of the actin cytoskeleton; a thorough understanding of the contribution of proteins regulating the spheroid actin cytoskeleton during cell-cell adhesions and adhesion to and transmigration through the peritoneal mesothelium is essential for progress in therapy of metastatic EOC. We showed that a panel of human EOC cells representing serous and clear cell adenocarcinomas express robust levels of mDia1 and mDia2 formins, irrespective of the ability to form compacted spheroids. mDia proteins were localized to the leading edge of migrating (spheroid-forming) serous epithelial OvCa 429 cells and disruption of mDia function inhibited this 2D chemotactic migration; conversely, dominant activated mDia2 in OvCa 429 cells enhanced chemotactic migration. Upon culture in 3D gels, both mDia1 and mDia2 are highly expressed and localized along with F-actin to the leading invasive edges of the compacted spheroids. Confocal analysis of single cell migration away from the spheroids revealed that multiple motility programs are employed by EOC cells- including single cell streaming and amoeboid cell motility. These data indicate a potential role for mDia proteins in driving localized invasion of EOC cells from compacted spheroids, and EOC cells exhibit a morphological plasticity while migrating in 3-dimensions. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 484. doi:1538-7445.AM2012-484
Association of IFN-γ and IFN regulatory factor 1 polymorphisms with childhood atopic asthma
Authors: Futoshi Nakao, Kenji Ihara, Koichi Kusuhara, Yuka Sasaki, Naoko Kinukawa, Akira Takabayashi, Sankei Nishima, Toshiro Hara
Journal: Journal of Allergy and Clinical Immunology (2001)
Treatment of itching in atopic eczema with antihistamines with a low sedative profile.
Authors: V. Doherty, D. G. Sylvester, C. T. Kennedy, S. G. Harvey, J. G. Calthrop, J. R. Gibson
Journal: BMJ (1989)

Etude sur 49 malades ambulatoires, avec placebo. Il semble que l'acrivastine et la terfenadine soient capables de diminuer le prurit, sans effet sedatif indesirable, et qu'ils renforcent l'action des traitements locaux (corticoides, emollients)
Antibody-selected mimics of hepatitis C virus hypervariable region 1 activate both primary and memory Th lymphocytes
Authors: Loredana Frasca, Cristiano Scottà, Paola Del Porto, Alfredo Nicosia, Caterina Pasquazzi, Ilaria Versace, Anna Maria Masci, Luigi Racioppi, Enza Piccolella
Journal: Hepatology (2003)

An ideal strategy that leads to a vaccine aimed at controlling viral escape may be that of preventing the replication of escape mutants by eliciting a T– and B–cell repertoire directed against many viral variants. The hypervariable region 1 (HVR1) of the putative envelope 2 protein that presents B and T epitopes shown to induce protective immunity against hepatitis C virus (HCV), might be suitable for this purpose if its immunogenicity can be improved by generating mimics that induce broad, highly cross–reactive, anti–HVR1 responses. Recently we described a successful approach to select HVR1 mimics (mimotopes) incorporating the variability found in a great number of viral variants. In this report we explore whether these mimotopes, designed to mimic B–cell epitopes, also mimic helper T–cell epitopes. The first interesting observation is that mimotopes selected for their reactivity to HVR1–specific antibodies of infected patients also do express HVR1 T–cell epitopes, suggesting that similar constraints govern HVR1–specific humoral and cellular immune responses. Moreover, some HVR1 mimotopes stimulate a multispecific CD4 + T–cell repertoire that effectively cross–reacts with HVR1 native sequences. This may significantly limit effects as a T–cell receptor (TCR) antagonist frequently exerted by natural HVR1–variants on HVR1–specific T–cell responses. In conclusion, these data lend strong support to using HVR1 mimotopes in vaccines designed to prevent replication of escape mutants.
Pressure Transmission in Pulmonary Arteries Related to Frequency and Geometry
Authors: ERNST O. ATTINGER
Journal: Circulation Research (1963)

The propagation of the pulse wave through the canine pulmonary arterial tree has been evaluated by means of harmonic analysis. The apparent phase velocity varied both with frequency and distance as one would expect in the presence of reflected waves. The phase velocity was about 230 cm/sec for the inflated and 325 cm/sec for the deflated lung. Theoretical considerations as well as experimental results indicate that the major branches represent the primary reflection site for the pulse wave. The pulse pressure is transmitted across the pulmonary capillary bed, although at a high attenuation, and the transmission varies markedly with lung volume. The dimensions of the pulmonary arterial tree were evaluated from casts. Data for the length and cross sections of the various branches are given. The volume of the arterial tree as represented by the casts was 24 ml. The cross section of the various branches represents an ellipse rather than a circle, and the cross section ratios of the major branch points is considerably less than those postulated for optimal energy transfer. The implications of the geometrical findings for the relation between pressure gradient and flow are briefly discussed.
A Scenario on the Stepwise Evolution of the Genetic Code
Authors: Jing-Fa Xiao, Jun Yu
Journal: Genomics Proteomics & Bioinformatics (2007)

Abstract It is believed that in the RNA world the operational (ribozymes) and the informational (riboscripts) RNA molecules were created with only three (adenosine, uridine, and guanosine) and two (adenosine and uridine) nucleosides, respectively, so that the genetic code started uncomplicated. Ribozymes subsequently evolved to be able to cut and paste themselves and riboscripts were acceptive to rigorous editing (adenosine to inosine); the intensive diversification of RNA molecules shaped novel cellular machineries that are capable of polymerizing amino acids—a new type of cellular building materials for life. Initially, the genetic code, encoding seven amino acids, was created only to distinguish purine and pyrimidine; it was later expanded in a stepwise way to encode 12, 15, and 20 amino acids through the relief of guanine from its roles as operational signals and through the recruitment of cytosine. Therefore, the maturation of the genetic code also coincided with (1) the departure of aminoacyl-tRNA synthetases (AARSs) from the primordial translation machinery, (2) the replacement of informational RNA by DNA, and (3) the co-evolution of AARSs and their cognate tRNAs. This model predicts gradual replacements of RNA-made molecular mechanisms, cellular processes by proteins, and informational exploitation by DNA.
Rationality and illusion
Authors: Jonathan Baron
Journal: Behavioral and Brain Sciences (2002)

Commitment to a pattern of altruism or self-control may indeed be learnable and sometimes rational. Commitment may also result from illusions. In one illusion, people think that their present behavior causes their future behavior, or causes the behavior of others, when really only correlation is present. Another happy illusion is that morality and self-interest coincide, so that altruism appears self-interested.
Sweet Success, but an Acid Aftertaste?
Authors: Lois Jovanovic-Peterson, Charles M. Peterson
Journal: New England Journal of Medicine (1991)

Since the advent of insulin in 1922, treatment programs designed to normalize the plasma glucose concentrations of pregnant women with diabetes have led to remarkable improvements in perinatal mortality.1 These results stimulated the state of California to start a program, called "Sweet Success," that was designed to help diabetic women achieve normoglycemia throughout pregnancy. Even so, poor outcomes continue to occur despite vigorous efforts. Do our present methods of management provide sufficient surveillance for diabetic women and their unborn children? Should clinicians, for example, pay more attention to maternal hypoglycemia, an invariable concomitant of the intensive management of diabetes? In . . .
Effect of Shock Wave–Facilitated Intracoronary Cell Therapy on LVEF in Patients With Chronic Heart Failure
Authors: Birgit Assmus, Dirk H. Walter, Florian H. Seeger, David M. Leistner, Julia Steiner, Ina Ziegler, Andreas Lutz, Walaa Khaled, Jens Klotsche, Torsten Tonn, Stefanie Dimmeler, Andreas M. Zeiher
Journal: JAMA (2013)

The modest effects of clinical studies using intracoronary administration of autologous bone marrow-derived mononuclear cells (BMCs) in patients with chronic postinfarction heart failure may be attributed to impaired homing of BMCs to the target area. Extracorporeal shock wave treatment has been experimentally shown to increase homing factors in the target tissue, resulting in enhanced retention of applied BMCs.To test the hypothesis that targeted cardiac shock wave pretreatment with subsequent application of BMCs improves recovery of left ventricular ejection fraction (LVEF) in patients with chronic heart failure.The CELLWAVE double-blind, randomized, placebo-controlled trial conducted among patients with chronic heart failure treated at Goethe University Frankfurt, Germany, between 2006 and 2011.Single-blind low-dose (n = 42), high-dose (n = 40), or placebo (n = 21) shock wave pretreatment targeted to the left ventricular anterior wall. Twenty-four hours later, patients receiving shock wave pretreatment were randomized to receive double-blind intracoronary infusion of BMCs or placebo, and patients receiving placebo shock wave received intracoronary infusion of BMCs.Primary end point was change in LVEF from baseline to 4 months in the pooled groups shock wave + placebo infusion vs shock wave + BMCs; secondary end points included regional left ventricular function assessed by magnetic resonance imaging and clinical events.The primary end point was significantly improved in the shock wave + BMCs group (absolute change in LVEF, 3.2% [95% CI, 2.0% to 4.4%]), compared with the shock wave + placebo infusion group (1.0% [95% CI, -0.3% to 2.2%]) (P = .02). Regional wall thickening improved significantly in the shock wave + BMCs group (3.6% [95% CI, 2.0% to 5.2%]) but not in the shock wave + placebo infusion group (0.5% [95% CI, -1.2% to 2.1%]) (P = .01). Overall occurrence of major adverse cardiac events was significantly less frequent in the shock wave + BMCs group (n = 32 events) compared with the placebo shock wave + BMCs (n = 18) and shock wave + placebo infusion (n = 61) groups (hazard ratio, 0.58 [95% CI, 0.40-0.85]; P = .02).Among patients with postinfarction chronic heart failure, shock wave-facilitated intracoronary administration of BMCs vs shock wave treatment alone resulted in a significant, albeit modest, improvement in LVEF at 4 months. Determining whether the increase in contractile function will translate into improved clinical outcomes requires confirmation in larger clinical end point trials.clinicaltrials.gov Identifier: NCT00326989.
Multimodal analgesia is central to alleviating pain in pancreatic adenocarcinoma
Authors: T. R. Shaikh, P. Desai
Journal: BMJ (2012)

Pancreatic adenocarcinoma is characterised by its late presentation and poor prognosis,1 with only 10-20% of cases being amenable to resection. Most patients will fall under the remit of palliative care. The treatment of pain merits particular attention because 50-70% of patients will have severe, difficult …
Imaging the rejecting heart. In vivo detection of major histocompatibility complex class II antigen induction.
Authors: M Isobe, J Narula, J F Southern, H W Strauss, B A Khaw, E Haber
Journal: Circulation (1992)

BACKGROUND Mice with abdominal heterotopic heart transplants were studied to determine whether scintigraphic detection of an increase in major histocompatibility complex (MHC) class II antigen expression could be used as a noninvasive method for diagnosing early rejection. METHODS AND RESULTS Allografts from C3H/He (H2k) donors were transplanted into BALB/c (H2d) recipients (n = 18). Two of the 18 allografted mice were treated with cyclosporine (15 mg/kg/day), and two isografted mice served as controls. Each mouse was injected intravenously with 100 microCi of 111In-labeled anti-MHC class II monoclonal antibodies (10-2-16 and 14-4-4S) 24 hours before scintigraphy. After imaging, the mice were killed for tissue counting and histopathology. Radiotracer uptake in the grafts reflected the severity of rejection as determined by histopathological criteria. The percent injected dose per gram of tissue in excised grafts was 4.8 +/- 1.8 (mean +/- SD) for normal grafts (n = 8), 11.1 +/- 9.7 for grafts with grade IA rejection (n = 3, NS), 18.0 +/- 3.8 for grafts with grade IIIA rejection (n = 4, p less than 0.001 versus normal), 18.7 +/- 3.2 for grafts with grade IIIB rejection (n = 3, p less than 0.001 versus normal), and 22.6 +/- 5.4 for grafts with severe rejection (grade IV) (n = 3, p less than 0.001 versus normal). Rejecting allografts with lymphocyte infiltration but without significant myocyte necrosis could be identified by this scintigraphic method. In the BALB/c donor-C57BL/6 (H2b, IE-) recipient combination, rejecting allografts were visualized by 14-4-4S (anti-IEk,d,p,r) antibody but not by 10-2-16 (anti-IAk,r,s,f) antibody. This difference shows that class II antigens induced on donor hearts are solely responsible for the antibody uptake in positive scintigrams of rejecting allografts. CONCLUSIONS We conclude that 111In-labeled anti-MHC class II antigen antibody imaging is a sensitive and noninvasive method for detecting cardiac allograft rejection.
The Autopsy in the Age of Molecular Biology
Authors: Charles S. Davidson
Journal: JAMA (1965)

The "old days" of anatomic and morphologic pathology are surely over, for this is the age of molecular biology. Such great morphologists as Virchow, Rokitansky, and those who followed contributed extensively to our knowledge of disease of the morphologic understanding of cancer and its metastases, of myocardial infarction and its relation to coronary blood flow, of peptic ulcer and the complications of perforation and hemorrhage, of the varieties of cirrhosis, and the classification of the leukemias and lymphomas. Much of our understanding of phenomona such as inflammation and necrosis is the result of long, careful, intelligent observation deriving mostly from the autopsy table. Undoubtedly, refinement in microscopy, especially of the electron microscope, will bring a better understanding of subcellular particles and ultra-structure, but in spite of all the knowledge that gross and microscopic pathology has taught us in the past, today search for the causes of disease is devoted to
A Phase I Trial of Ad.hIFN-β Gene Therapy for Glioma
Authors: E Antonio Chiocca, Katie M Smith, Byron McKinney, Cheryl A Palmer, Steven Rosenfeld, Kevin Lillehei, Allan Hamilton, Betty K DeMasters, Kevin Judy, David Kirn
Journal: Molecular Therapy (2008)

Interferon-β (IFN-β) is a pleiotropic cytokine with antitumoral activity. In an effort to improve the therapeutic index of IFN-β by providing local, sustained delivery of IFN-β to gliomas, the safety and biological activity of a human IFN-β (hIFN-β)-expressing adenovirus vector (Ad.hIFN-β) was evaluated in patients with malignant glioma by stereotactic injection, followed 4–8 days later by surgical removal of tumor with additional injections of Ad.hIFN-β into the tumor bed. Eleven patients received Ad.hIFN-β in cohorts of 2 × 1010, 6 × 1010, or 2 × 1011 vector particles (vp). The most common adverse events were considered by the investigator as being unrelated to treatment. One patient, who was enrolled in the cohort with the highest dose levels, experienced dose-limiting, treatment-related Grade 4 confusion following the post-operative injection. Ad.hIFN-β DNA was detected within the tumor, blood, and nasal swabs in a dose-dependent fashion and hIFN-β protein was detectable within the tumor. At the highest doses tested, a reproducible increase in tumor cell apoptosis in post-treatment versus pre-treatment biopsies with associated tumor necrosis was observed. Direct Ad.hIFN-β injection into the tumor and the surrounding normal brain areas after surgical removal was feasible and associated with apoptosis induction. Interferon-β (IFN-β) is a pleiotropic cytokine with antitumoral activity. In an effort to improve the therapeutic index of IFN-β by providing local, sustained delivery of IFN-β to gliomas, the safety and biological activity of a human IFN-β (hIFN-β)-expressing adenovirus vector (Ad.hIFN-β) was evaluated in patients with malignant glioma by stereotactic injection, followed 4–8 days later by surgical removal of tumor with additional injections of Ad.hIFN-β into the tumor bed. Eleven patients received Ad.hIFN-β in cohorts of 2 × 1010, 6 × 1010, or 2 × 1011 vector particles (vp). The most common adverse events were considered by the investigator as being unrelated to treatment. One patient, who was enrolled in the cohort with the highest dose levels, experienced dose-limiting, treatment-related Grade 4 confusion following the post-operative injection. Ad.hIFN-β DNA was detected within the tumor, blood, and nasal swabs in a dose-dependent fashion and hIFN-β protein was detectable within the tumor. At the highest doses tested, a reproducible increase in tumor cell apoptosis in post-treatment versus pre-treatment biopsies with associated tumor necrosis was observed. Direct Ad.hIFN-β injection into the tumor and the surrounding normal brain areas after surgical removal was feasible and associated with apoptosis induction.
Temperament and Behavior Disorders in Children
Authors: Stuart M. Finch
Journal: JAMA (1968)

This book, the latest resulting from the authors' longitudinal study of a group of young children, is basically oriented toward impressing the reader with the importance of the "temperament" in the emotional development of the child. The sample chosen represents 42 of the original 136 children in the study. These youngsters developed some symptom or other behavioral problem and were subsequently studied in detail. Nine categories of "reactivity" were utilized to establish the basic "temperament" of each subject. These categories were activity level, rhythmicity, approach or withdrawal, adaptability, intensity of reaction, threshold of responsiveness, quality of mood, distractibility, and attention span and persistence. Each of these was rated on a three-point scale. The ratings were begun in infancy and continued throughout childhood. The investigators also studied the homes of the children, their intellectual levels, and the reports from teachers. The sample consisted of children of various ages ranging from those
British doctors call for independent scrutiny of Guantanamo Bay detainees
Authors: Caroline White
Journal: BMJ (2006)

A group of British doctors has fiercely criticised the Foreign Office for what they term its “shameful silence” on the detainees held at Guantanamo Bay, which “reflects the collusion of this country in a war crime,” they say.

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British doctors have condemned the Foreign Office for failing to send a medical team to visit British residents held at Guantanamo 

Credit: BRENNAN LINSLEY/EMPICS

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MEDICINE AND THE SEA AFFAIR: INTRODUCTION
Authors: A. May
Journal: BMJ (1917)

THIS outline of the work of the medical service of the Royal Navy, necessarily brief from the exigencies of space, may well be"prefaced with the satisfa'ctory stte-- ment that thehealth of the service afloat has been excel- 'lent-better, indeed, thian in times of peace.This fortunate result is-due to several factors'.in the'first place, to the effots'' 'bf preventive medicine and' hygiene; especially the improved ventilation of warships introduced shortly before 'the outbre'ak of war, a subject more fully deal; with oa- pp.537-539; in tlle second place, to the healthy isolation -of 'the Grand Fleet, far from the temptations of seaports;